940 results on '"Array comparative genomic hybridization"'
Search Results
2. Amplifications of EVX2 and HOXD9-HOXD13 on 2q31 in mature cystic teratomas of the ovary identified by array comparative genomic hybridization may explain teratoma characteristics in chondrogenesis and osteogenesis
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Wen-Chung Wang, Tai-Cheng Hou, Chen-Yun Kuo, and Yen-Chein Lai
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Mature cystic teratoma of the ovary ,Array comparative genomic hybridization ,Chondrogenesis ,Osteogenesis ,Gynecology and obstetrics ,RG1-991 - Abstract
Abstract Background Teratomas are a common type of germ cell tumor. However, only a few reports on their genomic constitution have been published. The study of teratomas may provide a better understanding of their stepwise differentiation processes and molecular bases, which could prove useful for the development of tissue-engineering technologies. Methods In the present study, we analyzed the copy number aberrations of nine ovarian mature cystic teratomas using array comparative genomic hybridization in an attempt to reveal their genomic aberrations. Results The many chromosomal aberrations observed on array comparative genomic hybridization analysis reveal the complex genetics of this tumor. Amplifications and deletions of large DNA fragments were observed in some samples, while amplifications of EVX2 and HOXD9-HOXD13 on 2q31.1, NDUFV1 on 11q13.2, and RPL10, SNORA70, DNASE1L1, TAZ, ATP6AP1, and GDI1 on Xq28 were found in all nine mature cystic teratomas. Conclusions Our results indicated that amplifications of these genes may play an important etiological role in teratoma formation. Moreover, amplifications of EVX2 and HOXD9-HOXD13 on 2q31.1, found on array comparative genomic hybridization, may help to explain the characteristics of teratomas in chondrogenesis and osteogenesis.
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- 2024
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3. Amplifications of EVX2 and HOXD9-HOXD13 on 2q31 in mature cystic teratomas of the ovary identified by array comparative genomic hybridization may explain teratoma characteristics in chondrogenesis and osteogenesis.
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Wang, Wen-Chung, Hou, Tai-Cheng, Kuo, Chen-Yun, and Lai, Yen-Chein
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COMPARATIVE genomic hybridization , *TERATOMA , *GERM cell tumors , *CHONDROGENESIS ,TUMOR genetics - Abstract
Background: Teratomas are a common type of germ cell tumor. However, only a few reports on their genomic constitution have been published. The study of teratomas may provide a better understanding of their stepwise differentiation processes and molecular bases, which could prove useful for the development of tissue-engineering technologies. Methods: In the present study, we analyzed the copy number aberrations of nine ovarian mature cystic teratomas using array comparative genomic hybridization in an attempt to reveal their genomic aberrations. Results: The many chromosomal aberrations observed on array comparative genomic hybridization analysis reveal the complex genetics of this tumor. Amplifications and deletions of large DNA fragments were observed in some samples, while amplifications of EVX2 and HOXD9-HOXD13 on 2q31.1, NDUFV1 on 11q13.2, and RPL10, SNORA70, DNASE1L1, TAZ, ATP6AP1, and GDI1 on Xq28 were found in all nine mature cystic teratomas. Conclusions: Our results indicated that amplifications of these genes may play an important etiological role in teratoma formation. Moreover, amplifications of EVX2 and HOXD9-HOXD13 on 2q31.1, found on array comparative genomic hybridization, may help to explain the characteristics of teratomas in chondrogenesis and osteogenesis. Summary: Nine ovarian mature cystic teratomas were analyzed by aCGH. The amplifications of EVX2 and HOXD9-HOXD13 on 2q31.1 can be used to explain the characteristics of teratomas in chondrogenesis and osteogenesis. [ABSTRACT FROM AUTHOR]
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- 2024
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4. Impact of copy number variants in epilepsy plus neurodevelopment disorders.
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João, Sofia, Quental, Rita, Pinto, Joel, Almeida, Carolina, Santos, Helena, and Dória, Sofia
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• 22 of 146 patients (15 %) with epilepsy showed relevant copy number variants (CNVs). • "Epilepsy and global developmental delay/intellectual disability " group showed the highest prevalence of clinically relevant CNVs. • Chromosomes 1, 2, 16, and X showed higher CNVs incidence. • aCGH is a suitable first-line genetic test for the epilepsy-plus subgroup. • This study highlights the significance of aCGH in unraveling the genetic basis of epilepsy and have implications for precision medicine. Epilepsy, a neurological disorder characterized by recurring unprovoked seizures due to excessive neuronal excitability, is primarily attributed to genetic factors, accounting for an estimated 70 % of cases. Array-comparative genomic hybridization (aCGH) is a crucial genetic test for detecting copy number variants (CNVs) associated with epilepsy. This study aimed to analyze a cohort of epilepsy patients with CNVs detected through aCGH to enhance our understanding of the genetic underpinnings of epilepsy. A retrospective cross-sectional study was conducted using the aCGH database from the Genetics Department of the Faculty of Medicine of the University of Porto, encompassing 146 patients diagnosed with epilepsy, epileptic encephalopathy, or seizures. Clinical data were collected, and aCGH was performed following established guidelines. CNVs were classified based on ACMG standards, and patients were categorized into four groups according to their clinical phenotype. Among the 146 included patients, 94 (64 %) had at least one CNV, with 22 (15.1 %) classified as pathogenic or likely pathogenic. Chromosomes 1, 2, 16, and X were frequently implicated, with Xp22.33 being the most reported region (8 CNVs). The phenotype "Epilepsy and global developmental delay/intellectual disability" showed the highest prevalence of clinically relevant CNVs. Various CNVs were identified across different groups, suggesting potential roles in epilepsy. This study highlights the significance of aCGH in unraveling the genetic basis of epilepsy and tailoring treatment strategies. It contributes valuable insights to the expanding knowledge in the field, emphasizing the need for research to elucidate the diverse genetic causes of epilepsy. [ABSTRACT FROM AUTHOR]
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- 2024
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5. NUP214 fusion genes in acute leukemias: genetic characterization of rare cases.
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Brunetti, Marta, Andersen, Kristin, Spetalen, Signe, Lenartova, Andrea, Nygård Osnes, Liv Toril, Vålerhaugen, Helen, Heim, Sverre, and Micci, Francesca
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GENE fusion ,ACUTE leukemia ,NUCLEOTIDE sequencing ,COMPARATIVE genomic hybridization ,CHROMOSOME banding - Abstract
Introduction: Alterations of the NUP214 gene (9q34) are recurrent in acute leukemias. Rearrangements of chromosomal band 9q34 targeting this locus can be karyotypically distinct, for example t(6;9)(p22;q34)/DEK::NUP214, or cryptic, in which case no visible change of 9q34 is seen by chromosome banding. Methods: We examined 9 cases of acute leukemia with NUP214 rearrangement by array Comparative Genomic Hybridization (aCGH), reverse-transcription polymerase chain reaction (RT-PCR), and cycle sequencing/Sanger sequencing to detect which fusion genes had been generated. Results: The chimeras DEK::NUP214, SET::NUP214, and NUP214::ABL1 were found, only the first of which can be readily detected by karyotyping. Discussion: The identification of a specific NUP214 rearrangement is fundamental in the management of these patients, i.e., AMLs with DEK::NUP214 are classified as an adverse risk group and might be considered for allogenic transplant. Genome- and/or transcriptome-based next generation sequencing (NGS) techniques can be used to screen for these fusions, but we hereby present an alternative, step-wise procedure to detect these rearrangements. [ABSTRACT FROM AUTHOR]
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- 2024
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6. Prenatal diagnosis of isolated bilateral clubfoot: Is amniocentesis indicated?
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Leyne, Edouard, Anselem, Olivia, Jordan, Pénélope, Vivanti, Alexandre J., Benachi, Alexandra, Salomon, Laurent, Jacquier, Mathilde, Jouannic, Jean‐Marie, Dhombres, Ferdinand, Cambier, Tatiana, Rosenblatt, Jonathan, Pannier, Emmanuelle, Goffinet, François, Tsatsaris, Vassilis, and Athiel, Yoann
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PRENATAL diagnosis , *CLUBFOOT , *AMNIOCENTESIS , *DIGEORGE syndrome , *NEUROMUSCULAR diseases , *MYASTHENIA gravis , *22Q11 deletion syndrome - Abstract
Introduction: The aim of this study is to evaluate the benefit of cytogenetic testing by amniocentesis after an ultrasound diagnosis of isolated bilateral talipes equinovarus. Material and methods: This multicenter observational retrospective study includes all prenatally diagnosed cases of isolated bilateral talipes equinovarus in five fetal medicine centers from 2012 through 2021. Ultrasound data, amniocentesis results, biochemical analyses of amniotic fluid and parental blood samples to test neuromuscular diseases, pregnancy outcomes, and postnatal outcomes were collected for each patient. Results: In all, 214 fetuses with isolated bilateral talipes equinovarus were analyzed. A first‐degree family history of talipes equinovarus existed in 9.8% (21/214) of our cohort. Amniocentesis was proposed to 86.0% (184/214) and performed in 70.1% (129/184) of cases. Of the 184 karyotypes performed, two (1.6%) were abnormal (one trisomy 21 and one triple X syndrome). Of the 103 microarrays performed, two (1.9%) revealed a pathogenic copy number variation (one with a de novo 18p deletion and one with a de novo 22q11.2 deletion) (DiGeorge syndrome). Neuromuscular diseases (spinal muscular amyotrophy, myasthenia gravis, and Steinert disease) were tested for in 56 fetuses (27.6%); all were negative. Overall, 97.6% (165/169) of fetuses were live‐born, and the diagnosis of isolated bilateral talipes equinovarus was confirmed for 98.6% (139/141). Three medical terminations of pregnancy were performed (for the fetuses diagnosed with Down syndrome, DiGeorge syndrome, and the 18p deletion). Telephone calls (at a mean follow‐up age of 4.5 years) were made to all parents to collect medium‐term and long‐term follow‐up information, and 70 (33.0%) families were successfully contacted. Two reported a rare genetic disease diagnosed postnatally (one primary microcephaly and one infantile glycine encephalopathy). Parents did not report any noticeably abnormal psychomotor development among the other children during this data collection. Conclusions: Despite the low rate of pathogenic chromosomal abnormalities diagnosed prenatally after this ultrasound diagnosis, the risk of chromosomal aberration exceeds the risks of amniocentesis. These data may be helpful in prenatal counseling situations. [ABSTRACT FROM AUTHOR]
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- 2024
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7. Comprehensive chromosomal screening for preimplantation genetic testing: A mini-review.
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Sharma, Priyal, Jain, Manish, and Halder, Ashutosh
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BLASTOMERES ,SEQUENCE analysis ,DNA ,HUMAN genome ,MISCARRIAGE ,PREIMPLANTATION genetic diagnosis ,GENETIC testing ,GENETIC disorders ,EMBRYO transfer ,PREGNANCY outcomes ,INFERTILITY ,CHROMOSOME abnormalities ,INFECTIOUS disease transmission ,FERTILIZATION in vitro - Abstract
Preimplantation genetic testing (PGT) consists of a group of genetic tests to evaluate preimplantation embryos before transfer to the uterus during in vitro fertilization (IVF). It effectively reduces the incidence of genetic defects at birth by preventing the transmission of inherited diseases to embryos. The use of PGT in IVF clinics has greatly improved clinical pregnancy outcomes for carriers of genetic abnormalities through the selection of embryos that are free from any genetic mutation/chromosomal anomalies. However, the accuracy of PGT in detecting aneuploidies and genetic mutations remains a point of contention due to the varied effectiveness of the techniques used. In recent years, a number of high-throughput assays have been developed to overcome the challenges associated with comprehensive chromosomal analysis. In this review, we will summaries the recent progress in using comprehensive chromosomal screening techniques, including array comparative genomic hybridization, single nucleotide polymorphism array, and next-generation sequencing, to evaluate chromosomal genetic defects. [ABSTRACT FROM AUTHOR]
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- 2023
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8. NUP214 fusion genes in acute leukemias: genetic characterization of rare cases
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Marta Brunetti, Kristin Andersen, Signe Spetalen, Andrea Lenartova, Liv Toril Nygård Osnes, Helen Vålerhaugen, Sverre Heim, and Francesca Micci
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acute leukemias ,rare leukemias ,cytogenetics ,9q34-NUP214 ,fluorescence in situ hybridization ,array comparative genomic hybridization ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
IntroductionAlterations of the NUP214 gene (9q34) are recurrent in acute leukemias. Rearrangements of chromosomal band 9q34 targeting this locus can be karyotypically distinct, for example t(6;9)(p22;q34)/DEK::NUP214, or cryptic, in which case no visible change of 9q34 is seen by chromosome banding.MethodsWe examined 9 cases of acute leukemia with NUP214 rearrangement by array Comparative Genomic Hybridization (aCGH), reverse-transcription polymerase chain reaction (RT-PCR), and cycle sequencing/Sanger sequencing to detect which fusion genes had been generated.ResultsThe chimeras DEK::NUP214, SET::NUP214, and NUP214::ABL1 were found, only the first of which can be readily detected by karyotyping.DiscussionThe identification of a specific NUP214 rearrangement is fundamental in the management of these patients, i.e., AMLs with DEK::NUP214 are classified as an adverse risk group and might be considered for allogenic transplant. Genome- and/or transcriptome-based next generation sequencing (NGS) techniques can be used to screen for these fusions, but we hereby present an alternative, step-wise procedure to detect these rearrangements.
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- 2024
- Full Text
- View/download PDF
9. Diagnostic yield and clinical impact of chromosomal microarray analysis in autism spectrum disorder.
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Cucinotta, Francesca, Lintas, Carla, Tomaiuolo, Pasquale, Baccarin, Marco, Picinelli, Chiara, Castronovo, Paola, Sacco, Roberto, Piras, Ignazio Stefano, Turriziani, Laura, Ricciardello, Arianna, Scattoni, Maria Luisa, and Persico, Antonio M.
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AUTISM spectrum disorders , *DNA copy number variations , *SPECTRUM analysis , *AUTISTIC children , *AUTISM in children , *ASSISTED suicide - Abstract
Background: Autism spectrum disorder (ASD) is characterized by high heritability estimates and recurrence rates; its genetic underpinnings are very heterogeneous and include variable combinations of common and rare variants. Array‐comparative genomic hybridization (aCGH) offers significant sensitivity for the identification of copy number variants (CNVs), which can act as susceptibility or causal factors for ASD. Methods: The aim of this study was to evaluate both diagnostic yield and clinical impact of aCGH in 329 ASD patients of Italian descent. Results: Pathogenic/likely pathogenic CNVs were identified in 50/329 (15.2%) patients, whereas 89/329 (27.1%) carry variants of uncertain significance. The 10 most enriched gene sets identified by Gene Ontology Enrichment Analysis are primarily involved in neuronal function and synaptic connectivity. In 13/50 (26.0%) patients with pathogenic/likely pathogenic CNVs, the outcome of array‐CGH led to the request of 25 additional medical exams which would not have otherwise been prescribed, mainly including brain MRI, EEG, EKG, and/or cardiac ultrasound. A positive outcome was obtained in 12/25 (48.0%) of these additional tests. Conclusions: This study confirms the satisfactory diagnostic yield of aCGH, underscoring its potential for better, more in‐depth care of children with autism when genetic results are analyzed also with a focus on patient management. [ABSTRACT FROM AUTHOR]
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- 2023
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10. Prenatal Chromosomal Microarray Analysis: Does Increased Resolution Equal Increased Yield?
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Mitrakos, Anastasios, Kosma, Konstantina, Makrythanasis, Periklis, and Tzetis, Maria
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DNA copy number variations , *PRENATAL diagnosis , *COMPARATIVE genomic hybridization , *DEVELOPMENTAL disabilities , *CHORIONIC villi , *FETUS - Abstract
Chromosomal microarray analysis (CMA) is considered a first-tier test for patients with developmental disabilities and congenital anomalies and is also routinely applied in prenatal diagnosis. The current consensus size cut-off for reporting copy number variants (CNVs) in the prenatal setting ranges from 200 Kb to 400 Kb, with the intention of minimizing the impact of variants of uncertain significance (VUS). Very limited data are currently available on the application of higher resolution platforms prenatally. The aim of this study is to investigate the feasibility and impact of applying high-resolution CMA in the prenatal setting. To that end, we report on the outcomes of applying CMA with a size cut-off of 20 Kb in 250 prenatal samples and discuss the findings and diagnostic yield and also provide follow-up for cases with variants of uncertain significance. Overall, 19.6% (49) showed one or more chromosomal abnormalities, with the findings classified as Pathogenic (P) or Likely Pathogenic (LP) in 15.6% and as VUS in 4%. When excluding the cases with known familial aberrations, the diagnostic yield was 12%. The smallest aberration detected was a 32 Kb duplication of the 16p11.2 region. In conclusion, this study demonstrates that prenatal diagnosis with a high-resolution aCGH platform can reliably detect smaller CNVs that are often associated with neurodevelopmental phenotypes while providing an increased diagnostic yield, regardless of the indication for testing, with only a marginal increase in the VUS incidence. Thus, it can be an important tool in the prenatal setting. [ABSTRACT FROM AUTHOR]
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- 2023
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11. Diagnostic yield and clinical impact of chromosomal microarray analysis in autism spectrum disorder
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Francesca Cucinotta, Carla Lintas, Pasquale Tomaiuolo, Marco Baccarin, Chiara Picinelli, Paola Castronovo, Roberto Sacco, Ignazio Stefano Piras, Laura Turriziani, Arianna Ricciardello, Maria Luisa Scattoni, and Antonio M. Persico
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15q11.2–q13.1 duplication syndrome ,16p11.2 microdeletion syndrome ,array comparative genomic hybridization ,autism spectrum disorder ,copy number variants ,gene set enrichment analysis ,Genetics ,QH426-470 - Abstract
Abstract Background Autism spectrum disorder (ASD) is characterized by high heritability estimates and recurrence rates; its genetic underpinnings are very heterogeneous and include variable combinations of common and rare variants. Array‐comparative genomic hybridization (aCGH) offers significant sensitivity for the identification of copy number variants (CNVs), which can act as susceptibility or causal factors for ASD. Methods The aim of this study was to evaluate both diagnostic yield and clinical impact of aCGH in 329 ASD patients of Italian descent. Results Pathogenic/likely pathogenic CNVs were identified in 50/329 (15.2%) patients, whereas 89/329 (27.1%) carry variants of uncertain significance. The 10 most enriched gene sets identified by Gene Ontology Enrichment Analysis are primarily involved in neuronal function and synaptic connectivity. In 13/50 (26.0%) patients with pathogenic/likely pathogenic CNVs, the outcome of array‐CGH led to the request of 25 additional medical exams which would not have otherwise been prescribed, mainly including brain MRI, EEG, EKG, and/or cardiac ultrasound. A positive outcome was obtained in 12/25 (48.0%) of these additional tests. Conclusions This study confirms the satisfactory diagnostic yield of aCGH, underscoring its potential for better, more in‐depth care of children with autism when genetic results are analyzed also with a focus on patient management.
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- 2023
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12. Identification of Extremely Rare Pathogenic CNVs by Array CGH in Saudi Children with Developmental Delay, Congenital Malformations, and Intellectual Disability.
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Karim, Sajjad, Hussein, Ibtessam Ramzi, Schulten, Hans-Juergen, Alsaedi, Saad, Mirza, Zeenat, Al-Qahtani, Mohammed, and Chaudhary, Adeel
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REVERSE transcriptase polymerase chain reaction ,ANEUPLOIDY ,22Q11 deletion syndrome ,NUCLEIC acid hybridization ,DEVELOPMENTAL disabilities ,HUMAN abnormalities ,KARYOTYPES ,CHROMOSOME abnormalities ,RESEARCH funding ,INTELLECTUAL disabilities ,RARE diseases ,DISEASE risk factors ,DISEASE complications - Abstract
Chromosomal imbalance is implicated in developmental delay (DD), congenital malformations (CM), and intellectual disability (ID), and, thus, precise identification of copy number variations (CNVs) is essential. We therefore aimed to investigate the genetic heterogeneity in Saudi children with DD/CM/ID. High-resolution array comparative genomic hybridization (array CGH) was used to detect disease-associated CNVs in 63 patients. Quantitative PCR was done to confirm the detected CNVs. Giemsa banding-based karyotyping was also performed. Array CGH identified chromosomal abnormalities in 24 patients; distinct pathogenic and/or variants of uncertain significance CNVs were found in 19 patients, and aneuploidy was found in 5 patients including 47,XXY (n = 2), 45,X (n = 2) and a patient with trisomy 18 who carried a balanced Robertsonian translocation. CNVs including 9p24p13, 16p13p11, 18p11 had gains/duplications and CNVs, including 3p23p14, 10q26, 11p15, 11q24q25, 13q21.1q32.1, 16p13.3p11.2, and 20q11.1q13.2, had losses/deletions only, while CNVs including 8q24, 11q12, 15q25q26, 16q21q23, and 22q11q13 were found with both gains or losses in different individuals. In contrast, standard karyotyping detected chromosomal abnormalities in ten patients. The diagnosis rate of array CGH (28%, 18/63 patients) was around two-fold higher than that of conventional karyotyping (15.87%, 10/63 patients). We herein report, for the first time, the extremely rare pathogenic CNVs in Saudi children with DD/CM/ID. The reported prevalence of CNVs in Saudi Arabia adds value to clinical cytogenetics. [ABSTRACT FROM AUTHOR]
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- 2023
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13. Prenatal diagnosis of distal 13q deletion syndrome in a fetus with esophageal atresia: a case report and review of the literature
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Tomomi Kotani, Hiroyuki Tsuda, Yumiko Ito, Noriyuki Nakamura, Takafumi Ushida, Kenji Imai, Yukako Iitani, Kazuya Fuma, Yukako Muramatsu, Masahiro Hayakawa, and Hiroaki Kajiyama
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Array comparative genomic hybridization ,Esophageal atresia ,Prenatal diagnosis ,Medicine - Abstract
Abstract Background Chromosome 13q deletion syndrome shows variable clinical features related to the different potential breakpoints in chromosome 13q. The severely malformed phenotype is known to be associated with the deletion of a critical region in 13q32. However, esophageal atresia is a rare symptom and the relevant region is unknown. Thus, determining the association between accurate breakpoints and new clinical features is essential. Case presentation A 28-year-old Japanese primigravid woman was referred for fetal growth restriction, absence of a gastric bubble, cerebellar hypoplasia, overlapping fingers, and polyhydramnios at 31 weeks gestation. At 38 + 0 weeks, she delivered a 1774 g female infant. The infant presented with isolated esophageal atresia (Gross type A), Dandy–Walker malformation, right microphthalmia, left coloboma, overlapping fingers, pleurocentrum in the thoracic vertebrae, reduced anogenital distance, and hearing loss. Her karyotype was diagnosed as 46,XX,del(13)(q32.1–qter) by amniocentesis, but array comparative genomic hybridization after birth revealed the deletion of 13q31.3–qter. At 48 days after birth, the infant underwent surgery for esophageal atresia and was later discharged from the hospital at 7 months of age. Conclusion This case report and the literature reviews supports the previous findings on the pathological roles of haploinsufficiency of the ZIC2/ZIC5 in Dandy–Walker malformation and the EFBN2 haploinsufficiency in eye malformation and hearing loss. Furthermore, the possible involvement of IRS2, COLA1, and COLA2 in eye malformation were identified. This is the first case of 13q deletion syndrome with esophageal atresia (Gross A), but it may be a symptom of VATER/VACTER association (vertebral defects, anorectal malformations, cardiac defects, tracheoesophageal fistula with or without esophageal atresia, renal malformations, and limb defects), as in the previous cases. These symptoms might also be associated with EFBN2 haploinsufficiency, although further research is required.
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- 2022
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14. Xp22.33p22.13 Duplication in a Male Patient Carrying a Recombinant X Chromosome Derived from an Inherited Intrachromosomal Insertion.
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Joaquim, Tatiana Mozer, Roy, Scott David, de Albuquerque, Clarissa Gondim Picanço, Grangeiro, Carlos Henrique Paiva, Squire, Jeremy A., Yoshimoto, Maisa, and Martelli, Lucia
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X chromosome , *COMPARATIVE genomic hybridization , *FLUORESCENCE in situ hybridization , *DEVELOPMENTAL delay , *INTELLECTUAL disabilities - Abstract
Intrachromosomal insertions are complex structural rearrangements that are challenging to interpret using classical cytogenetic methods. We report a male patient carrying a recombinant X chromosome derived from a maternally inherited intrachromosomal insertion. The patient exhibited developmental delay, intellectual disability, behavioral disorder, and dysmorphic facial features. To accurately identify the rearrangements in the abnormal X chromosome, additional cytogenetic studies were conducted, including fluorescence in situ hybridization (FISH), multicolor-banding FISH, and array comparative genomic hybridization. The results showed a recombinant X chromosome, resulting in a 13.05 Mb interstitial duplication of segment Xp22.33–Xp22.13, which was inserted at cytoband Xq26.1. The duplicated region encompasses 99 genes, some of which are associated with the patient's clinical manifestations. We propose that the combined effects of the Xp-duplicated genes may contribute to the patient's phenotype. [ABSTRACT FROM AUTHOR]
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- 2023
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15. Incidental Detection of a Chromosomal Aberration by Array-CGH in an Early Prenatal Diagnosis for Monogenic Disease on Coelomic Fluid.
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Vinciguerra, Margherita, Leto, Filippo, Cassarà, Filippo, Tartaglia, Viviana, Malacarne, Michela, Coviello, Domenico, Cigna, Valentina, Orlandi, Emanuela, Picciotto, Francesco, Cucinella, Gaspare, Salzano, Emanuela, Piccione, Maria, Maggio, Aurelio, and Giambona, Antonino
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CHROMOSOME abnormalities , *PRENATAL diagnosis , *X chromosome , *KARYOTYPES , *DIAGNOSIS , *COMPARATIVE genomic hybridization , *MICROSATELLITE repeats - Abstract
Background: Turner syndrome is a rare genetic condition in which a female is partly or completely missing an X chromosome. Signs and symptoms vary among those affected. In fetuses that survive at birth and without congenital malformations, the prognosis is usually positive, but it has high lethality in utero, especially in the first trimester of pregnancy. Methods: We report a case of monosomy X detected during a prenatal diagnosis for beta thalassemia on coelomic fluid (CF) at the VIII week of gestation. Beta globin gene analysis, whole genome amplification (WGA), quantitative fluorescent PCR and array comparative genomic hybridization (array-CGH) were performed on DNA extracted from CF. Results: A monoallelic pattern of all Short Tandem Repeats mapped on the X chromosome was found and array-CGH performed on WGA from a few fetal erythroblasts confirmed monosomy X. Conclusion: This report underlines the importance of an early prenatal diagnosis and the countless potentialities of array-CGH that could make definition of molecular karyotype possible from a few fetal cells, unlike conventional cytogenetic techniques that require a greater cellular content. This is the first report of a molecular karyotype obtained from two cells selected by micromanipulation of CF and defined at such an early gestational age. [ABSTRACT FROM AUTHOR]
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- 2023
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16. Y-chromosome genes associated with sertoli cell-only syndrome identified by array comparative genome hybridization
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Kuo-Chung Lan, Hung-Jen Wang, Tzu-Jou Wang, Hsin-Jung Lin, Yung-Chiao Chang, and Hong-Yo Kang
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Azoospermia ,Array comparative genomic hybridization ,Genetic variations ,Sertoli cell-only syndrome ,Spermatogenesis ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
Background: The precise contribution of each chromosome gene or gene family in achieving male fertility is still the subject of debate. Most studies have examined male populations with heterogeneous causes of infertility, and have therefore reached controversial or uncertain conclusions. This study uses Y-chromosome array-based comparative genomic hybridization (aCGH) to examine a population of males with a uniform sertoli cell-only syndrome (SCOS) infertility phenotype. Methods: Initial analysis of gene copy number variations in 8 SCOS patients, with determination of the log-ratio of probe signal intensity against a DNA reference, was performed using the Y-chromosome NimbleGen aCGH. To confirm the role of candidate genes, real-time quantitative RT-PCR was used to compare 19 patients who had SCOS non-obstructive azoospermia with 15 patients who had obstructive azoospermia but normal spermatogenesis. Results: Our initial aCGH experiments identified CDY1a and CDY1b double deletions in all 8 patients who had total germ cell depletion. However, 5 patients had DAZ1/2 and DAZ3/4 deletions, 1 patient had a DAZ2 and DAZ3/4 deletion, and 2 patients had no DAZ1/2 or DAZ3/4 deletions. Examination of testicular mRNA expression in another 19 patients with SCOS indicated all patients had no detectable levels of CDY1. Conclusions: Our findings indicate that CDY1 deletion in SCOS patients, and analysis of the expression of DAZ and CDY1 genes using aCGH and quantitative RT-PCR, may be useful to predict the presence of mature spermatozoa.
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- 2023
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17. Noninvasive Prenatal Diagnostics: Recent Developments Using Circulating Fetal Nucleated Cells.
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Pin-Jung, Chen, Pai-Chi, Teng, Zhu, Yazhen, Jen Jan, Yu, Smalley, Matthew, Afshar, Yalda, Li-Ching, Chen, Pisarska, Margareta D, and Hsian-Rong, Tseng
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Array Comparative Genomic Hybridization ,Circulating Fetal Nucleated Red Blood Cell ,Circulating Trophoblast ,Noninvasive Prenatal Diagnostic ,Short Tandem Repeat ,Whole Genome Amplification ,Clinical Research ,Genetics ,Pediatric ,4.1 Discovery and preclinical testing of markers and technologies ,Detection ,screening and diagnosis ,Reproductive health and childbirth ,Noninvasive prenatal diagnostic ,Circulating fetal nucleated red blood cell ,Circulating trophoblast ,Whole genome amplification ,Array comparative genomic hybridization ,Short tandem repeat - Abstract
Purpose of reviewThe purpose of this review is to highlight recent research advances in noninvasive prenatal diagnostic methods.Recent findingsRecent studies developing noninvasive prenatal diagnostic (NIPD) methods have been focused on either fetal nucleated red blood cells (fNRBCs) or circulating trophoblasts (cTBs). Enriched cTBs were successfully utilized for whole genome profiling and short tandem repeat (STR) identification to confirm feto-maternal relationship. However, further analysis of isolated fNRBCs remains confined to examining fetal cytogenetics.SummaryInvasive prenatal diagnostic procedures, amniocentesis and chorionic villus sampling, are the gold standard for the diagnosis of fetal chromosomal abnormalities and genetic disorders. Meanwhile, noninvasive techniques of analyzing circulating cell-free fetal DNA (cffDNA) have been limited to screening tools and are highly fragmented and confounded by maternal DNA. By detecting circulating fetal nucleated cells (CFNCs) we are able to noninvasively confirm fetal chromosomal abnormalities, truly realizing the concept of "noninvasive prenatal diagnostics". The primary technical challenge is the enrichment of the low abundance of CFNCs in maternal peripheral blood. For any cell-based NIPD method, both fetal whole genome profiling and confirmation of the feto-parental relationship are essential. This has been successfully performed using enriched and isolated cTBs, making cTB a better candidate for NIPD. cTB enumeration also correlates with abnormal fetal or placental development. On the other hand, downstream analysis of fNRBCs remains limited to examining fetal sex and aneuploidies. Furthermore, trophoblast-based NIPD via an endocervical sample is also promising because of reduced dilution from hematologic cells.
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- 2019
18. Prenatal diagnosis of distal 13q deletion syndrome in a fetus with esophageal atresia: a case report and review of the literature.
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Kotani, Tomomi, Tsuda, Hiroyuki, Ito, Yumiko, Nakamura, Noriyuki, Ushida, Takafumi, Imai, Kenji, Iitani, Yukako, Fuma, Kazuya, Muramatsu, Yukako, Hayakawa, Masahiro, and Kajiyama, Hiroaki
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POLYHYDRAMNIOS , *COMPARATIVE genomic hybridization , *ESOPHAGEAL fistula , *PRENATAL diagnosis , *FETAL growth retardation , *HOSPITAL admission & discharge ,ESOPHAGEAL atresia - Abstract
Background: Chromosome 13q deletion syndrome shows variable clinical features related to the different potential breakpoints in chromosome 13q. The severely malformed phenotype is known to be associated with the deletion of a critical region in 13q32. However, esophageal atresia is a rare symptom and the relevant region is unknown. Thus, determining the association between accurate breakpoints and new clinical features is essential. Case presentation: A 28-year-old Japanese primigravid woman was referred for fetal growth restriction, absence of a gastric bubble, cerebellar hypoplasia, overlapping fingers, and polyhydramnios at 31 weeks gestation. At 38 + 0 weeks, she delivered a 1774 g female infant. The infant presented with isolated esophageal atresia (Gross type A), Dandy–Walker malformation, right microphthalmia, left coloboma, overlapping fingers, pleurocentrum in the thoracic vertebrae, reduced anogenital distance, and hearing loss. Her karyotype was diagnosed as 46,XX,del(13)(q32.1–qter) by amniocentesis, but array comparative genomic hybridization after birth revealed the deletion of 13q31.3–qter. At 48 days after birth, the infant underwent surgery for esophageal atresia and was later discharged from the hospital at 7 months of age. Conclusion: This case report and the literature reviews supports the previous findings on the pathological roles of haploinsufficiency of the ZIC2/ZIC5 in Dandy–Walker malformation and the EFBN2 haploinsufficiency in eye malformation and hearing loss. Furthermore, the possible involvement of IRS2, COLA1, and COLA2 in eye malformation were identified. This is the first case of 13q deletion syndrome with esophageal atresia (Gross A), but it may be a symptom of VATER/VACTER association (vertebral defects, anorectal malformations, cardiac defects, tracheoesophageal fistula with or without esophageal atresia, renal malformations, and limb defects), as in the previous cases. These symptoms might also be associated with EFBN2 haploinsufficiency, although further research is required. [ABSTRACT FROM AUTHOR]
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- 2022
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19. Prenatal Chromosomal Microarray Analysis: Does Increased Resolution Equal Increased Yield?
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Anastasios Mitrakos, Konstantina Kosma, Periklis Makrythanasis, and Maria Tzetis
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prenatal diagnosis ,amniotic fluid ,chorionic villi ,array comparative genomic hybridization ,aCGH ,Genetics ,QH426-470 - Abstract
Chromosomal microarray analysis (CMA) is considered a first-tier test for patients with developmental disabilities and congenital anomalies and is also routinely applied in prenatal diagnosis. The current consensus size cut-off for reporting copy number variants (CNVs) in the prenatal setting ranges from 200 Kb to 400 Kb, with the intention of minimizing the impact of variants of uncertain significance (VUS). Very limited data are currently available on the application of higher resolution platforms prenatally. The aim of this study is to investigate the feasibility and impact of applying high-resolution CMA in the prenatal setting. To that end, we report on the outcomes of applying CMA with a size cut-off of 20 Kb in 250 prenatal samples and discuss the findings and diagnostic yield and also provide follow-up for cases with variants of uncertain significance. Overall, 19.6% (49) showed one or more chromosomal abnormalities, with the findings classified as Pathogenic (P) or Likely Pathogenic (LP) in 15.6% and as VUS in 4%. When excluding the cases with known familial aberrations, the diagnostic yield was 12%. The smallest aberration detected was a 32 Kb duplication of the 16p11.2 region. In conclusion, this study demonstrates that prenatal diagnosis with a high-resolution aCGH platform can reliably detect smaller CNVs that are often associated with neurodevelopmental phenotypes while providing an increased diagnostic yield, regardless of the indication for testing, with only a marginal increase in the VUS incidence. Thus, it can be an important tool in the prenatal setting.
- Published
- 2023
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20. Cancer Comprehensive Analysis in Gastric Carcinoma: Benefits and New Perspectives
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Vasiliki Pisanidou, Panagiotis Apostolou, Georgios Beis, Eleana Hatzidaki, and Ioannis Papasotiriou
- Subjects
gastrointestinal cancer ,array comparative genomic hybridization ,next-generation sequencing ,microarrays ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Gastric cancer is one of the most common and deadly cancers worldwide. Screening tests as well as tools for prediction of treatment outcomes and prognosis have been developed, but they have many limitations. The integration of liquid biopsy provided new aspects in screening and diagnosis of gastric cancer. In the present study, we used different techniques, studying the genetic and epigenetic profile of circulating tumor cells. We aimed to acquire all the available information, compare it with already existing studies, and evaluate the benefit of this approach. A blood sample was isolated from 2 gastric cancer patients at stages III–IV, followed by the isolation of CTCs. The circulating tumor cells were used for array comparative genomic hybridization, next-generation sequencing, and whole gene expression microarrays. Different variants were detected, while the microsatellite instability status was stable in both cases. The tumor mutational burden was low to medium. Gene expression assays revealed that >100 genes were overexpressed compared to noncancer samples. Amplifications of X chromosome were also observed in both cases, by using array comparative genomic hybridization. Although there are several techniques for cancer screening, prediction of therapy outcomes, and prognosis, the application of a complete comprehensive cancer panel, combining the study of variants, fusions, chromosomal abnormalities, and gene expression, is more appropriate. Information provided by the above techniques might contribute in designing more efficient treatment protocols and screening tools. Despite the limitation of samples, the data are encouraging, and further study is needed so that they can be used at clinical level.
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- 2021
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21. Application of machine learning to predict aneuploidy and mosaicism in embryos from in vitro fertilization cyclesAJOG Global Reports at a Glance
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José A. Ortiz, PhD, Ruth Morales, PhD, Belén Lledó, PhD, Juan A. Vicente, PhD, Julio González, PhD, Eva M. García-Hernández, PhD, Alba Cascales, MSc, Jorge Ten, PhD, Andrea Bernabeu, PhD, MD, and Rafael Bernabeu, PhD, MD
- Subjects
array comparative genomic hybridization ,artificial intelligence ,embryo aneuploidy ,embryo mosaicism ,machine learning ,next-generation sequencing ,Gynecology and obstetrics ,RG1-991 - Abstract
BACKGROUND: The factors associated with embryo aneuploidy have been extensively studied. Mostly maternal age and to a lesser extent male factor and ovarian stimulation have been related to the occurrence of chromosomal alterations in the embryo. On the other hand, the main factors that may increase the incidence of embryo mosaicism have not yet been established. OBJECTIVE: This study aimed to establish a machine learning model that would allow prediction of aneuploidies and mosaicism in embryos conceived via in vitro fertilization, and thus help to determine which variables are associated with these chromosomal alterations. STUDY DESIGN: The study design was observational and retrospective. A total of 6989 embryos from 2476 cycles of preimplantation genetic testing for aneuploidies were included (January 2013 to December 2020). The trophoectoderm biopsies on day-5, -6, or -7 blastocysts were analyzed by preimplantation genetic testing for aneuploidies (PGT-A). The different maternal, paternal, couple, embryo, and in vitro fertilization cycle characteristics were recorded in a database (22 predictor variables) from which predictive models of embryo aneuploidy and mosaicism were developed; 16 different unsupervised classification machine learning algorithms were used to establish the predictive models. RESULTS: Two different predictive models were performed: one for aneuploidy and the other for mosaicism. The predictor variable was of multiclass type because it included the segmental- and whole-chromosome alteration categories. The best predicting models for both aneuploidies and mosaicism were those obtained from the Random Forest algorithm. The area under ROC curve (AUC) value was 0.792 for the aneuploidy explanatory model and 0.776 for mosaicism. The most important variable in the final aneuploidy model was maternal age, followed by paternal and maternal karyotype and embryo quality. In the predictive model of mosaicism, the most important variable was the technique used in preimplantation genetic testing for aneuploidies and embryo quality, followed by maternal age and day of biopsy. CONCLUSION: It is possible to predict embryo aneuploidy and mosaicism from certain characteristics of the patients and their embryos.
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- 2022
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22. Discovery of Long Non-Coding RNA MALAT1 Amplification in Precancerous Colorectal Lesions.
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Siskova, Anna, Kral, Jan, Drabova, Jana, Cervena, Klara, Tomasova, Kristyna, Jungwirth, Jiri, Hucl, Tomas, Kohout, Pavel, Summerova, Sandra, Vodickova, Ludmila, Vodicka, Pavel, and Vymetalkova, Veronika
- Subjects
- *
LINCRNA , *ADENOMATOUS polyps , *PRECANCEROUS conditions , *COMPARATIVE genomic hybridization , *CANCER cell migration , *CHROMOSOME abnormalities - Abstract
A colorectal adenoma, an aberrantly growing tissue, arises from the intestinal epithelium and is considered as precursor of colorectal cancer (CRC). In this study, we investigated structural and numerical chromosomal aberrations in adenomas, hypothesizing that chromosomal instability (CIN) occurs early in adenomas. We applied array comparative genomic hybridization (aCGH) to fresh frozen colorectal adenomas and their adjacent mucosa from 16 patients who underwent colonoscopy examination. In our study, histologically similar colorectal adenomas showed wide variability in chromosomal instability. Based on the obtained results, we further stratified patients into four distinct groups. The first group showed the gain of MALAT1 and TALAM1, long non-coding RNAs (lncRNAs). The second group involved patients with numerous microdeletions. The third group consisted of patients with a disrupted karyotype. The fourth group of patients did not show any CIN in adenomas. Overall, we identified frequent losses in genes, such as TSC2, COL1A1, NOTCH1, MIR4673, and GNAS, and gene gain containing MALAT1 and TALAM1. Since long non-coding RNA MALAT1 is associated with cancer cell metastasis and migration, its gene amplification represents an important event for adenoma development. [ABSTRACT FROM AUTHOR]
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- 2022
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23. Clinical Findings on Chromosome 1 Copy Number Variations.
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Leitão, Filipa, Grangeia, Ana, Pinto, Joel, Passas, Armanda, and Dória, Sofia
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22Q11 deletion syndrome , *CHROMOSOMES - Abstract
These patients share several features with our patient, including DD (5 patients), scoliosis (4 patients), strabismus, and hypotonia (2 patients). [19] In patient 14 the deletion was more distal and corresponded only partially to the interval described in the 1q21.1 microdeletion syndrome, consequently, it was not clear if the deletion could explain the phenotype and was classified as LP. Keywords: chromosome 1; copy number variant; array comparative genomic hybridization; neurodevelopmental disorders; 1q21.1 syndrome EN chromosome 1 copy number variant array comparative genomic hybridization neurodevelopmental disorders 1q21.1 syndrome 265 273 9 09/07/22 20220701 NES 220701 Conflict of Interest None declared. [21] The DECIPHER database describes several patients with deletions that partially overlap with our patient CNV and sharing several features with our patient, including ID, language impairment, muscular hypotonia, and macrocephaly. [Extracted from the article]
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- 2022
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24. Imprinted NanoVelcro Microchips for Isolation and Characterization of Circulating Fetal Trophoblasts: Toward Noninvasive Prenatal Diagnostics
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Hou, Shuang, Chen, Jie-Fu, Song, Min, Zhu, Yazhen, Jan, Yu Jen, Chen, Szu Hao, Weng, Tzu-Hua, Ling, Dean-An, Chen, Shang-Fu, Ro, Tracy, Liang, An-Jou, Lee, Tom, Jin, Helen, Li, Man, Liu, Lian, Hsiao, Yu-Sheng, Chen, Peilin, Yu, Hsiao-Hua, Tsai, Ming-Song, Pisarska, Margareta D, Chen, Angela, Chen, Li-Ching, and Tseng, Hsian-Rong
- Subjects
Clinical Research ,Perinatal Period - Conditions Originating in Perinatal Period ,Genetics ,Human Genome ,Pediatric ,Biotechnology ,Reproductive health and childbirth ,Adolescent ,Adult ,Comparative Genomic Hybridization ,DNA ,Female ,Genetic Testing ,Humans ,Immunohistochemistry ,Male ,Trisomy ,Trophoblasts ,Young Adult ,noninvasive prenatal testing ,nanoVelcro assays ,circulating trophoblasts ,single-cell analysis ,array comparative genomic hybridization ,Nanoscience & Nanotechnology - Abstract
Circulating fetal nucleated cells (CFNCs) in maternal blood offer an ideal source of fetal genomic DNA for noninvasive prenatal diagnostics (NIPD). We developed a class of nanoVelcro microchips to effectively enrich a subcategory of CFNCs, i.e., circulating trophoblasts (cTBs) from maternal blood, which can then be isolated with single-cell resolution by a laser capture microdissection (LCM) technique for downstream genetic testing. We first established a nanoimprinting fabrication process to prepare the LCM-compatible nanoVelcro substrates. Using an optimized cTB-capture condition and an immunocytochemistry protocol, we were able to identify and isolate single cTBs (Hoechst+/CK7+/HLA-G+/CD45-, 20 μm > sizes > 12 μm) on the imprinted nanoVelcro microchips. Three cTBs were polled to ensure reproducible whole genome amplification on the cTB-derived DNA, paving the way for cTB-based array comparative genomic hybridization (aCGH) and short tandem repeats analysis. Using maternal blood samples collected from expectant mothers carrying a single fetus, the cTB-derived aCGH data were able to detect fetal genders and chromosomal aberrations, which had been confirmed by standard clinical practice. Our results support the use of nanoVelcro microchips for cTB-based noninvasive prenatal genetic testing, which holds potential for further development toward future NIPD solution.
- Published
- 2017
25. Multiple Merkel cell carcinomas: Late metastasis or multiple primary tumors? A molecular study.
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Eluri, Madhulika, Feneran, Ashley, Bordeaux, Jeremy S, Ruben, Beth, Ostrowski, Stephen, Bastian, Boris C, and Honda, Kord
- Subjects
FFPE ,formalin-fixed paraffin-embedded ,MCC ,Merkel cell carcinoma ,MCpV ,Merkel cell polyomavirus ,Merkel cell carcinoma ,Merkel cell carcinoma metastasis ,PET/CT ,positron emission tomography/computed tomography ,SLNB ,sentinel lymph node biopsy ,aCGH ,array comparative genomic hybridization ,array comparative genomic hybridization ,multiple Merkel cell carcinoma ,FFPE ,formalin-fixed paraffin-embedded ,MCC ,MCpV ,Merkel cell polyomavirus ,PET/CT ,positron emission tomography/computed tomography ,SLNB ,sentinel lymph node biopsy ,aCGH - Published
- 2017
26. A placental trisomy 2 detected by NIPT evolved in a fetal small Supernumerary Marker Chromosome (sSMC)
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Justyna Domaradzka, Marta Deperas, Ewa Obersztyn, Anna Kucińska-Chahwan, Nathalie Brison, Kris Van Den Bogaert, Tomasz Roszkowski, Marta Kędzior, Magdalena Bartnik-Głaska, Alicja Łuszczek, Krystyna Jakubów-Durska, Joris Robert Vermeesch, and Beata Anna Nowakowska
- Subjects
Array comparative genomic hybridization ,Fluorescence in situ hybridization ,Karyotyping ,Mosaicism ,Non-invasive prenatal test ,Small supernumerary marker chromosome ,Genetics ,QH426-470 - Abstract
Abstract Background Non-invasive prenatal testing (NIPT) is a rapidly developing and widely used method in the prenatal screening. Recently, the widespread use of the NIPT caused a neglecting of the limitations of this technology. Case presentation The 38-year-old woman underwent amniocentesis because of a high risk of trisomy 2 revealed by the genome-wide Non-Invasive Prenatal Test (NIPT). The invasive prenatal diagnosis revealed the mosaicism for a small supernumerary marker chromosome sSMC derived from chromosome 2. Interphase fluorescence in situ hybridization (FISH) on uncultured amniocytes revealed three signals of centromere 2 in 30% of the cells. GTG-banded metaphases revealed abnormal karyotype (47,XX,+mar[21]/46,XX[19]) and was confirmed by array comparative genomic hybridization (aCGH). Cytogenetic analyses (FISH, aCGH, karyotype) on fetal skin biopsies were performed and confirmed the genomic gain of the centromeric region of chromosome 2. In the placenta, three cell lines were detected: a normal cell line, a cell line with trisomy 2 and a third one with only the sSMC. Conclusion Whole-genome Non-Invasive Prenatal Testing allows not only the identification of common fetal trisomies but also diagnosis of rare chromosomal abnormalities. Especially in such cases, it is extremely important to perform not only NIPT verification on a sample of material other than trophoblast, but also to apply appropriate research methods. Such conduct allows detailed analysis of the detected aberration, thus appropriate clinical validity.
- Published
- 2021
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27. Preimplantation Genetic Screening and The Success Rate of In Vitro Fertilization: A Three-Years Study on Iranian Population
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Mehdi Totonchi, Babak Babaabasi, Hadi Najafi, Mojtaba Rezazadeh Valojerdi, Poopak Eftekhari-Yazdi, Lila Karimian, Anahita Mohseni Meybodi, Morteza Kimiai, Mehri Mashayekhi, Tahereh Madani, and Hamid Gourabi
- Subjects
array comparative genomic hybridization ,assisted reproductive technology ,in vitro fertilization ,preimplantation genetic screening ,Medicine ,Science - Abstract
Objective: In vitro fertilization (IVF) is one of the most efficient approaches within the context of assisted reproductive technology (ART) to treat infertility. High pregnancy rates have become the major index of successful IVF in clinical studies. It is not clear yet which factors are certainly responsible for IVF success, as various outcomes were obtained in different IVF centers with different settings. In this study, we aimed to address controversies in the interpretation of promising results of IVF with respect to preimplantation genetic screening (PGS). Materials and Methods: In this retrospective case series study, we built a dataset containing data from 213 IVF patient candidates for PGS (654 embryos) with blastomere biopsy at day 3 and trophectoderm biopsy in day 5, referred to Royan Institute, Tehran, Iran from 2015 to 2018. Next, the data were analyzed to find influential factors affecting success rate of ART cycles. Results: Data analyses showed that regardless of PGS indications (ART failures, recurrent miscarriage, chromosomal abnormalities, etc.), the pregnancy rate is influenced by maternal and embryonic factors such as the age of mother as well as quantity and quality of transferred embryos. Furthermore, genotyping of embryos using array comparative genomic hybridization (aCGH) depicted the highest rate of chromosomal aberrations for chromosomes 1, 16 and 19 while the lowest frequency for chromosomes 11 and 17. Similarly, we detected 463 genetically abnormal embryos by aCGH, among which only 41.9% could be detected by classical fluorescent in situ hybridization (FISH) method. Conclusion: This study not only highlighted the advantages of aCGH over the FISH method in detection of chromosomal abnormalities, but also emphasized the importance of genetic abnormality as an indication for determination of IVF success rate.
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- 2021
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28. An asymptomatic male individual carrying a 5.72 Mb de novo deletion in 8p23.2‑p23.3: A case report.
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Keramida, Christina, Papoulidis, Ioannis, Pappa, Efterpi, Liehr, Thomas, Kalmantis, Konstantinos, Gerede, Angeliki, Pavlidou, Efterpi, Petersen, Michael Bjorn, and Manolakos, Emmanouil
- Subjects
- *
ASYMPTOMATIC patients , *COMPARATIVE genomic hybridization , *EPILEPSY , *FLUORESCENCE in situ hybridization , *CHROMOSOMAL rearrangement , *INTELLECTUAL disabilities - Abstract
Numerous rearrangements in the 8p23 chromosomal region have been reported; included in these rearrangements are isolated deletions in this area. Such deletions are associated with a wide range of phenotypic characteristics, including motor impairment, epilepsy, intellectual disability, cardiac defects and seizures. The present study describes the case of a 30-year-old asymptomatic man that carries a de novo deletion in 8p23.2-p23.3. Molecular karyotyping indicated that the detected deletion involves genes that are in the critical region which is hypothesized to be responsible for the phenotypic characteristics associated with such deletions. The normal phenotype of the patient supports the hypothesis that there is incomplete penetrance of 8p23.2-p23.3 deletions. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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29. Identification of Extremely Rare Pathogenic CNVs by Array CGH in Saudi Children with Developmental Delay, Congenital Malformations, and Intellectual Disability
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Sajjad Karim, Ibtessam Ramzi Hussein, Hans-Juergen Schulten, Saad Alsaedi, Zeenat Mirza, Mohammed Al-Qahtani, and Adeel Chaudhary
- Subjects
array comparative genomic hybridization ,copy number variations ,developmental delay ,congenital malformations ,Saudi Arabia ,Pediatrics ,RJ1-570 - Abstract
Chromosomal imbalance is implicated in developmental delay (DD), congenital malformations (CM), and intellectual disability (ID), and, thus, precise identification of copy number variations (CNVs) is essential. We therefore aimed to investigate the genetic heterogeneity in Saudi children with DD/CM/ID. High-resolution array comparative genomic hybridization (array CGH) was used to detect disease-associated CNVs in 63 patients. Quantitative PCR was done to confirm the detected CNVs. Giemsa banding-based karyotyping was also performed. Array CGH identified chromosomal abnormalities in 24 patients; distinct pathogenic and/or variants of uncertain significance CNVs were found in 19 patients, and aneuploidy was found in 5 patients including 47,XXY (n = 2), 45,X (n = 2) and a patient with trisomy 18 who carried a balanced Robertsonian translocation. CNVs including 9p24p13, 16p13p11, 18p11 had gains/duplications and CNVs, including 3p23p14, 10q26, 11p15, 11q24q25, 13q21.1q32.1, 16p13.3p11.2, and 20q11.1q13.2, had losses/deletions only, while CNVs including 8q24, 11q12, 15q25q26, 16q21q23, and 22q11q13 were found with both gains or losses in different individuals. In contrast, standard karyotyping detected chromosomal abnormalities in ten patients. The diagnosis rate of array CGH (28%, 18/63 patients) was around two-fold higher than that of conventional karyotyping (15.87%, 10/63 patients). We herein report, for the first time, the extremely rare pathogenic CNVs in Saudi children with DD/CM/ID. The reported prevalence of CNVs in Saudi Arabia adds value to clinical cytogenetics.
- Published
- 2023
- Full Text
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30. Trypanosoma cruzi Genomic Variability: Array Comparative Genomic Hybridization Analysis of Clone and Parental Strain.
- Author
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Rodrigues Cortez, Danielle, Mitsuo Lima, Fabio, Luís Reis-Cunha, João, Castanheira Bartholomeu, Daniella, Rios Villacis, Rolando Andre, Rogatto, Silvia Regina, Guilherme Costa-Martins, André, Marchiano, Fernanda Sycko, Andrade do Carmo, Rafaela, Franco da Silveira, Jose, and Marini, Marjorie Mendes
- Abstract
Trypanosoma cruzi, the etiological agent of Chagas disease, exhibits extensive inter- and intrastrain genetic diversity. As we have previously described, there are some genetic differences between the parental G strain and its clone D11, which was isolated by the limiting dilution method and infection of cultured mammalian cells. Electrophoretic karyotyping and Southern blot hybridization of chromosomal bands with specific markers revealed chromosome length polymorphisms of small size with additional chromosomal bands in clone D11 and the maintenance of large syntenic groups. Both G strain and clone D11 belong to the T. cruzi lineage TcI. Here, we designed intraspecific array-based comparative genomic hybridization (aCGH) to identify chromosomal regions harboring copy-number variations between clone D11 and the G strain. DNA losses were more extensive than DNA gains in clone D11. Most alterations were flanked by repeated sequences from multigene families that could be involved in the duplication and deletion events. Several rearrangements were detected by chromoblot hybridization and confirmed by aCGH. We have integrated the information of genomic sequence data obtained by aCGH to the electrophoretic karyotype, allowing the reconstruction of possible recombination events that could have generated the karyotype of clone D11. These rearrangements may be explained by unequal crossing over between sister or homologous chromatids mediated by flanking repeated sequences and unequal homologous recombination via break-induced replication. The genomic changes detected by aCGH suggest the presence of a dynamic genome that responds to environmental stress by varying the number of gene copies and generating segmental aneuploidy. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
31. Diagnostic Utility of Array Comparative Genomic Hybridization in Children with Neurological Diseases.
- Author
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Cokyaman, Turgay and Silan, Fatma
- Subjects
- *
COMPARATIVE genomic hybridization , *JUVENILE diseases , *NEUROLOGICAL disorders , *BODY dysmorphic disorder , *CHILD patients - Abstract
We evaluated the contribution of array comparative genomic hybridization (aCGH) to the final diagnosis in children with neurocognitive disturbances or dysmorphic findings, but lacked a specific diagnosis. Medical files of pediatric patients with neurocognitive disturbances who underwent aCGH analysis were reviewed retrospectively. Of 155 patients, 77 copy number variations were detected and 50% (39/77) were considered causative. The aCGH's final diagnostic rate was 25.1% (39/155). With aCGH analysis, the diagnosis rate for patients with undiagnosed neurocognitive disturbances or dysmorphic syndrome may increase by 25–30%. If the phenotypic findings of the widely known neurocognitive disturbances cannot be identified during the initial clinical assessment, aCGH analysis may be beneficial. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
32. Trypanosoma cruzi Genomic Variability: Array Comparative Genomic Hybridization Analysis of Clone and Parental Strain
- Author
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Danielle Rodrigues Cortez, Fabio Mitsuo Lima, João Luís Reis-Cunha, Daniella Castanheira Bartholomeu, Rolando Andre Rios Villacis, Silvia Regina Rogatto, André Guilherme Costa-Martins, Fernanda Sycko Marchiano, Rafaela Andrade do Carmo, Jose Franco da Silveira, and Marjorie Mendes Marini
- Subjects
Trypanosoma cruzi ,intrastrain variability ,parental strain and clone ,karyotyping ,array comparative genomic hybridization ,gene copy number variation ,Microbiology ,QR1-502 - Abstract
Trypanosoma cruzi, the etiological agent of Chagas disease, exhibits extensive inter- and intrastrain genetic diversity. As we have previously described, there are some genetic differences between the parental G strain and its clone D11, which was isolated by the limiting dilution method and infection of cultured mammalian cells. Electrophoretic karyotyping and Southern blot hybridization of chromosomal bands with specific markers revealed chromosome length polymorphisms of small size with additional chromosomal bands in clone D11 and the maintenance of large syntenic groups. Both G strain and clone D11 belong to the T. cruzi lineage TcI. Here, we designed intraspecific array-based comparative genomic hybridization (aCGH) to identify chromosomal regions harboring copy-number variations between clone D11 and the G strain. DNA losses were more extensive than DNA gains in clone D11. Most alterations were flanked by repeated sequences from multigene families that could be involved in the duplication and deletion events. Several rearrangements were detected by chromoblot hybridization and confirmed by aCGH. We have integrated the information of genomic sequence data obtained by aCGH to the electrophoretic karyotype, allowing the reconstruction of possible recombination events that could have generated the karyotype of clone D11. These rearrangements may be explained by unequal crossing over between sister or homologous chromatids mediated by flanking repeated sequences and unequal homologous recombination via break-induced replication. The genomic changes detected by aCGH suggest the presence of a dynamic genome that responds to environmental stress by varying the number of gene copies and generating segmental aneuploidy.
- Published
- 2022
- Full Text
- View/download PDF
33. Identification of copy number variants in children and adolescents with autism spectrum disorder: a study from Turkey.
- Author
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Özaslan, Ahmet, Kayhan, Gülsüm, İşeri, Elvan, Ergün, Mehmet Ali, Güney, Esra, and Perçin, Ferda Emriye
- Abstract
Background: Copy number variants (CNVs) play a key role in the etiology of autism spectrum disorder (ASD). Therefore, recent guidelines recommend chromosomal microarrays (CMAs) as first-tier genetic tests. This study's first aim was to determine the clinical usefulness of CMAs in children diagnosed with ASD in a Turkish population. The second aim was to describe the CNVs and clinical phenotypes of children with ASD. Methods and Results: This was a single-center retrospective cross‐sectional study. Data were obtained from the medical records of children with ASD followed at Gazi University Hospital, (Ankara, Turkey). The sample consisted of 47 ASD cases (mean age: 60.34 ± 25.60 months; 82.9% boys). The diagnostic yield of the CMAs was 8.5%. Four pathogenic CNVs were identified: 9p24.3p24.2 deletion, 15q11–q13 duplication, 16p11.2 deletion, and 22q13.3 deletion. Also, four variants were found at 2q36.3, 10p11.21, 15q11.2, and Xp11.22, which were classified as variants of uncertain significance (VUS). Conclusions: The TRAP12 and PARD3 genes in CNVs classified as VUS may be worth investigating for autism. The initial identification of both clinical and biological markers can facilitate monitoring, early intervention, or prevention and advance our understanding of the neurobiology underlying ASD. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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34. Optic nerve coloboma as extension of the phenotype of 22q11.23 duplication syndrome: a case report
- Author
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Claudia Valencia-Peña, Paula Jiménez-Sanchez, Wilmar Saldarriaga, and César Payán-Gómez
- Subjects
Coloboma of optic nerve ,Duplication 22q11 q13 ,Bioinformatics ,Array comparative genomic hybridization ,Case report ,Ophthalmology ,RE1-994 - Abstract
Abstract Background 22q11.2 duplication syndrome (Dup22q11.2) has reduced penetrance and variable expressivity. Those affected may have intellectual disabilities, dysmorphic facial features, and ocular alterations such as ptosis, hypertelorism, nystagmus, and chorioretinal coloboma. The prevalence of this syndrome is unknown, there are only approximately 100 cases reported. However Dup22q11.2 should have a similar prevalence of DiGeorge syndrome (1 in each 4000 new-borns), in which the same chromosomal region that is duplicated in Dup22q11.2 is deleted. Case presentation We report a patient with intellectual disability, psychomotor development delay, hearing loss with disyllable pronunciation only, hyperactivity, self-harm, hetero-aggressive behaviour, facial dysmorphism, left facial paralysis, post-axial polydactyly, and for the first time in patients with Dup22q11.2, optic nerve coloboma and dysplasia in optic nerve. Array comparative genomic hybridization showed a 22q11.23 duplication of 1.306 million base pairs. Conclusions New ocular findings in Dup22q11.2 syndrome, such as coloboma and dysplasia in the optic nerve, are reported here, contributing to the phenotypic characterization of a rarely diagnosed genetic syndrome. A complete characterization of the phenotype is necessary to increase the rate of clinical suspicion and then the genetic diagnostic. In addition, through bioinformatics analysis of the genes mapped to the 22q11.2 region, it is proposed that deregulation of the SPECC1L gene could be implicated in the development of ocular coloboma.
- Published
- 2020
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35. Incidental Detection of a Chromosomal Aberration by Array-CGH in an Early Prenatal Diagnosis for Monogenic Disease on Coelomic Fluid
- Author
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Margherita Vinciguerra, Filippo Leto, Filippo Cassarà, Viviana Tartaglia, Michela Malacarne, Domenico Coviello, Valentina Cigna, Emanuela Orlandi, Francesco Picciotto, Gaspare Cucinella, Emanuela Salzano, Maria Piccione, Aurelio Maggio, and Antonino Giambona
- Subjects
prenatal diagnosis ,array comparative genomic hybridization ,coelocentesis ,monosomy X ,beta thalassemia ,Science - Abstract
Background: Turner syndrome is a rare genetic condition in which a female is partly or completely missing an X chromosome. Signs and symptoms vary among those affected. In fetuses that survive at birth and without congenital malformations, the prognosis is usually positive, but it has high lethality in utero, especially in the first trimester of pregnancy. Methods: We report a case of monosomy X detected during a prenatal diagnosis for beta thalassemia on coelomic fluid (CF) at the VIII week of gestation. Beta globin gene analysis, whole genome amplification (WGA), quantitative fluorescent PCR and array comparative genomic hybridization (array-CGH) were performed on DNA extracted from CF. Results: A monoallelic pattern of all Short Tandem Repeats mapped on the X chromosome was found and array-CGH performed on WGA from a few fetal erythroblasts confirmed monosomy X. Conclusion: This report underlines the importance of an early prenatal diagnosis and the countless potentialities of array-CGH that could make definition of molecular karyotype possible from a few fetal cells, unlike conventional cytogenetic techniques that require a greater cellular content. This is the first report of a molecular karyotype obtained from two cells selected by micromanipulation of CF and defined at such an early gestational age.
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- 2022
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36. Cancer Comprehensive Analysis in Gastric Carcinoma: Benefits and New Perspectives.
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Pisanidou, Vasiliki, Apostolou, Panagiotis, Beis, Georgios, Hatzidaki, Eleana, and Papasotiriou, Ioannis
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COMPARATIVE genomic hybridization , *STOMACH cancer , *CIRCULATING tumor DNA , *GENE expression , *X chromosome , *NUCLEOTIDE sequencing - Abstract
Gastric cancer is one of the most common and deadly cancers worldwide. Screening tests as well as tools for prediction of treatment outcomes and prognosis have been developed, but they have many limitations. The integration of liquid biopsy provided new aspects in screening and diagnosis of gastric cancer. In the present study, we used different techniques, studying the genetic and epigenetic profile of circulating tumor cells. We aimed to acquire all the available information, compare it with already existing studies, and evaluate the benefit of this approach. A blood sample was isolated from 2 gastric cancer patients at stages III–IV, followed by the isolation of CTCs. The circulating tumor cells were used for array comparative genomic hybridization, next-generation sequencing, and whole gene expression microarrays. Different variants were detected, while the microsatellite instability status was stable in both cases. The tumor mutational burden was low to medium. Gene expression assays revealed that >100 genes were overexpressed compared to noncancer samples. Amplifications of X chromosome were also observed in both cases, by using array comparative genomic hybridization. Although there are several techniques for cancer screening, prediction of therapy outcomes, and prognosis, the application of a complete comprehensive cancer panel, combining the study of variants, fusions, chromosomal abnormalities, and gene expression, is more appropriate. Information provided by the above techniques might contribute in designing more efficient treatment protocols and screening tools. Despite the limitation of samples, the data are encouraging, and further study is needed so that they can be used at clinical level. [ABSTRACT FROM AUTHOR]
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- 2021
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37. Discovery of Long Non-Coding RNA MALAT1 Amplification in Precancerous Colorectal Lesions
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Anna Siskova, Jan Kral, Jana Drabova, Klara Cervena, Kristyna Tomasova, Jiri Jungwirth, Tomas Hucl, Pavel Kohout, Sandra Summerova, Ludmila Vodickova, Pavel Vodicka, and Veronika Vymetalkova
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colorectal cancer ,adenomas ,array comparative genomic hybridization ,long non-coding RNA ,MALAT1 ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
A colorectal adenoma, an aberrantly growing tissue, arises from the intestinal epithelium and is considered as precursor of colorectal cancer (CRC). In this study, we investigated structural and numerical chromosomal aberrations in adenomas, hypothesizing that chromosomal instability (CIN) occurs early in adenomas. We applied array comparative genomic hybridization (aCGH) to fresh frozen colorectal adenomas and their adjacent mucosa from 16 patients who underwent colonoscopy examination. In our study, histologically similar colorectal adenomas showed wide variability in chromosomal instability. Based on the obtained results, we further stratified patients into four distinct groups. The first group showed the gain of MALAT1 and TALAM1, long non-coding RNAs (lncRNAs). The second group involved patients with numerous microdeletions. The third group consisted of patients with a disrupted karyotype. The fourth group of patients did not show any CIN in adenomas. Overall, we identified frequent losses in genes, such as TSC2, COL1A1, NOTCH1, MIR4673, and GNAS, and gene gain containing MALAT1 and TALAM1. Since long non-coding RNA MALAT1 is associated with cancer cell metastasis and migration, its gene amplification represents an important event for adenoma development.
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- 2022
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38. Investigation of Chromosomal Abnormalities and Microdeletion/Microduplication(s) in Fifty Iranian Patients with Multiple Congenital Anomalies
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Akbar Mohammadzadeh, Susan Akbaroghli, Ehsan Aghaei-Moghadam, Nejat Mahdieh, Reza Shervin Badv, Payman Jamali, Roxana Kariminejad, Zahra Chavoshzadeh, Saghar Ghasemi Firouzabadi, Roxana Mansour Ghanaie, Ahoura Nozari, Sussan Banihashemi, Fatemeh Hadipour, Zahra Hadipour, Ariana Kariminejad, Hossein Najmabadi, Yousef Shafeghati, and Farkhondeh Behjati
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Array Comparative Genomic Hybridization ,Chromosomal Abnormalities ,Congenital Abnormalities ,Microdeletions ,Multiplex Ligation-Dependent Probe Amplification ,Medicine ,Science - Abstract
Objective: Major birth defects are inborn structural or functional anomalies with long-term disability and adverse impacts on individuals, families, health-care systems, and societies. Approximately 20% of birth defects are due to chromosomal and genetic conditions. Inspired by the fact that neonatal deaths are caused by birth defects in about 20 and 10% of cases in Iran and worldwide respectively, we conducted the present study to unravel the role of chromosome abnormalities, including microdeletion/microduplication(s), in multiple congenital abnormalities in a number of Iranian patients. Materials and Methods: In this descriptive cross-sectional study, 50 sporadic patients with Multiple Congenital Anomalies (MCA) were selected. The techniques employed included conventional karyotyping, fluorescence in situ hybridization (FISH), multiplex ligation-dependent probe amplification (MLPA), and array comparative genomic hybridisation (array-CGH), according to the clinical diagnosis for each patient. Results: Chromosomal abnormalities and microdeletion/microduplication(s) were observed in eight out of fifty patients (16%). The abnormalities proved to result from the imbalances in chromosomes 1, 3, 12, and 18 in four of the patients. However, the other four patients were diagnosed to suffer from the known microdeletions of 22q11.21, 16p13.3, 5q35.3, and 7q11.23. Conclusion: In the present study, we report a patient with 46,XY, der(18)[12]/46,XY, der(18), +mar[8] dn presented with MCA associated with hypogammaglobulinemia. Given the patient’s seemingly rare and highly complex chromosomal abnormality and the lack of any concise mechanism presented in the literature to justify the case, we hereby propose a novel mechanism for the formation of both derivative and ring chromosome 18. In addition, we introduce a new 12q abnormality and a novel association of an Xp22.33 duplication with 1q43q44 deletion syndrome. The phenotype analysis of the patients with chromosome abnormality would be beneficial for further phenotype-genotype correlation studies.
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- 2019
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39. Embryonic aneuploidy after preimplantation genetic screening: Age- and indication-matched comparative study between Indian and Spanish population
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Aditi P Kotdawala, Pere Mir, Javier Herrero, Rajni Khajuria, P G. L. Lalitkumar, and Manish R Banker
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Aneuploidy ,array comparative genomic hybridization ,chromosome aberrations ,ethnic comparison ,preimplantation genetic screening ,Gynecology and obstetrics ,RG1-991 - Abstract
Background: Recent studies show that there are differences in female fertility in different ethnic groups with ovarian aging and IVF treatment outcomes. Advanced maternal age is a known risk factor for miscarriage, accounting largely due to genetically abnormal fetus. Aims and Objectives: This study investigates if there are any differences in rates of embryo aneuploidy based on age and indications for preimplantation genetic screening (PGS) between Indian and Spanish women. Materials and Methods: This multicenter study was carried out at fertility centers in India and Spain. Data from autologous IVF cycles of women
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- 2019
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40. Preimplantation genetic diagnosis and screening (PGD/S) using a semiconductor sequencing platform
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Li-Ya Wang, Xing-Qiang Rao, Yu-Qin Luo, Bei Liu, Chun-Fang Peng, Dan Chen, Kai Yan, Ye-Qing Qian, Yan-Mei Yang, Ying-Zhi Huang, Min Chen, Yi-Xi Sun, Hong-Ge Li, Ying-Hui Ye, Fan Jin, Hai-Liang Liu, and Min-Yue Dong
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Preimplantation genetic diagnosis/screening ,Semiconductor sequencing platform ,Array comparative genomic hybridization ,Whole genome amplification ,Copy number variation ,Medicine ,Genetics ,QH426-470 - Abstract
Abstract Background Recent advances in semiconductor sequencing platform (SSP) have provided new methods for preimplantation genetic diagnosis/screening (PGD/S). The present study aimed to evaluate the applicability and efficiency of SSP in PGD/S. Methods The artificial positive single-cell-like DNAs and normal single-cell samples were chosen to test our semiconductor sequencing platform for preimplantation genetic diagnosis/screening (SSP-PGD/S) method with two widely used whole-genome amplification (WGA) kits. A total of 557 single blastomeres were collected from in vitro fertilization (IVF) couples, and their WGA products were processed and analyzed by our SSP-PGD/S method in comparison with array comparative genomic hybridization (array-CGH). Results Our SSP-PGD/S method indicated high compatibilities with two commercial WGA kits. For 557 single blastomeres, our method with four million reads in average could detect 24-chromosome aneuploidies as well as microdeletion/microduplication of the size over 4 Mb, providing 100% consistent conclusion with array-CGH method in the classification of whether it was transplantable. Conclusions Our studies suggested that SSP-PGD/S represents a valuable alternative to array-CGH and brought PGD/S into a new era of more rapid, accurate, and economic.
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- 2019
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41. Trisomy 8 Mosaicism Syndrome
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Chen, Harold and Chen, Harold
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- 2017
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42. Advanced Computation of Sparse Precision Matrices for Big Data
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Baggag, Abdelkader, Bensmail, Halima, Srivastava, Jaideep, Hutchison, David, Series editor, Kanade, Takeo, Series editor, Kittler, Josef, Series editor, Kleinberg, Jon M., Series editor, Mattern, Friedemann, Series editor, Mitchell, John C., Series editor, Naor, Moni, Series editor, Pandu Rangan, C., Series editor, Steffen, Bernhard, Series editor, Terzopoulos, Demetri, Series editor, Tygar, Doug, Series editor, Weikum, Gerhard, Series editor, Kim, Jinho, editor, Shim, Kyuseok, editor, Cao, Longbing, editor, Lee, Jae-Gil, editor, Lin, Xuemin, editor, and Moon, Yang-Sae, editor
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- 2017
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43. A placental trisomy 2 detected by NIPT evolved in a fetal small Supernumerary Marker Chromosome (sSMC).
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Domaradzka, Justyna, Deperas, Marta, Obersztyn, Ewa, Kucińska-Chahwan, Anna, Brison, Nathalie, Van Den Bogaert, Kris, Roszkowski, Tomasz, Kędzior, Marta, Bartnik-Głaska, Magdalena, Łuszczek, Alicja, Jakubów-Durska, Krystyna, Vermeesch, Joris Robert, and Nowakowska, Beata Anna
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GENETIC markers , *COMPARATIVE genomic hybridization , *FLUORESCENCE in situ hybridization , *TRISOMY , *PRENATAL diagnosis , *CYTOGENETICS , *KARYOTYPES , *CHROMOSOME banding - Abstract
Background: Non-invasive prenatal testing (NIPT) is a rapidly developing and widely used method in the prenatal screening. Recently, the widespread use of the NIPT caused a neglecting of the limitations of this technology. Case presentation: The 38-year-old woman underwent amniocentesis because of a high risk of trisomy 2 revealed by the genome-wide Non-Invasive Prenatal Test (NIPT). The invasive prenatal diagnosis revealed the mosaicism for a small supernumerary marker chromosome sSMC derived from chromosome 2. Interphase fluorescence in situ hybridization (FISH) on uncultured amniocytes revealed three signals of centromere 2 in 30% of the cells. GTG-banded metaphases revealed abnormal karyotype (47,XX,+mar[21]/46,XX[19]) and was confirmed by array comparative genomic hybridization (aCGH). Cytogenetic analyses (FISH, aCGH, karyotype) on fetal skin biopsies were performed and confirmed the genomic gain of the centromeric region of chromosome 2. In the placenta, three cell lines were detected: a normal cell line, a cell line with trisomy 2 and a third one with only the sSMC. Conclusion: Whole-genome Non-Invasive Prenatal Testing allows not only the identification of common fetal trisomies but also diagnosis of rare chromosomal abnormalities. Especially in such cases, it is extremely important to perform not only NIPT verification on a sample of material other than trophoblast, but also to apply appropriate research methods. Such conduct allows detailed analysis of the detected aberration, thus appropriate clinical validity. [ABSTRACT FROM AUTHOR]
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- 2021
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44. A novel missense mutation in the UBE2A gene causes intellectual disability in the large X‐linked family.
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Arslan Satılmış, Saide Betül, Kurt, Emin Emre, Akçay, Ebru Perim, Sazci, Ali, and Ceylan, Ahmet Cevdet
- Abstract
Background: X‐linked intellectual disability type Nascimento (XIDTN) is a disorder of the ubiquitin‐proteasome pathway of protein degradation controlled by the UBE2A gene. The disease is characterized by intellectual disability, speech impairment, dysmorphic facial features, skin and nail anomalies, and, frequently, seizures. Eight affected males from a four‐generation family who have intellectual disability and speech disorders were examined within an extended family of 57 individuals. Methods A number of methods were used for the molecular diagnosis. Conventional karyotype analyses, array‐based comparative genomic hybridization (aCGH), whole exome swquencing (WES), sanger sequencing were performed. Results First, the conventional karyotype analyses were normal, and the results of the aCGH analyses were normal. Then, WES revealed a novel missense mutation of the UBE2A gene at exon 4 NM_003336.3: c.182A>G (p.Glu61Gly). Seven affected individuals and nine carriers in the multigenerational, large family were diagnosed through Sanger sequencing. Conclusions: We identified the mutation causing intellectual disability in the large family and demonstrated its phenotypic effects. Our cases showed that dysmorphic features could be considered mild, whereas intellectual disability and speech disorders are common features in XIDTN. The structure and function of the gene will be better understood in the novel UBE2A mutation. The genotype–phenotype correlation and phenotypic variations in XIDTN were identified through a literature review. Accordingly, XIDTN should be considered in individuals who exhibit an X‐linked pedigree pattern and have intellectual disability and speech disorders. [ABSTRACT FROM AUTHOR]
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- 2021
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45. Preimplantation Genetic Screening and The Success Rate of In Vitro Fertilization: A Three-Years Study on Iranian Population.
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Totonchi, Mehdi, Babaabasi, Babak, Najafi, Hadi, Valojerdi, Mojtaba Rezazadeh, Eftekhari-Yazdi, Poopak, Karimian, Lila, Almadani, Navid, Meybodi, Anahita Mohseni, Kimiai, Morteza, Mashayekhi, Mehri, Madani, Tahereh, and Gourabi, Hamid
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GENETIC testing , *HUMAN in vitro fertilization , *EMBRYO transfer , *COMPARATIVE genomic hybridization , *FLUORESCENCE in situ hybridization , *CHROMOSOME abnormalities , *RECURRENT miscarriage , *FERTILIZATION in vitro - Abstract
Objective: In vitro fertilization (IVF) is one of the most efficient approaches within the context of assisted reproductive technology (ART) to treat infertility. High pregnancy rates have become the major index of successful IVF in clinical studies. It is not clear yet which factors are certainly responsible for IVF success, as various outcomes were obtained in different IVF centers with different settings. In this study, we aimed to address controversies in the interpretation of promising results of IVF with respect to preimplantation genetic screening (PGS). Materials and Methods: In this retrospective case series study, we built a dataset containing data from 213 IVF patient candidates for PGS (654 embryos) with blastomere biopsy at day 3 and trophectoderm biopsy in day 5, referred to Royan Institute, Tehran, Iran from 2015 to 2018. Next, the data were analyzed to find influential factors affecting success rate of ART cycles. Results: Data analyses showed that regardless of PGS indications (ART failures, recurrent miscarriage, chromosomal abnormalities, etc.), the pregnancy rate is influenced by maternal and embryonic factors such as the age of mother as well as quantity and quality of transferred embryos. Furthermore, genotyping of embryos using array comparative genomic hybridization (aCGH) depicted the highest rate of chromosomal aberrations for chromosomes 1, 16 and 19 while the lowest frequency for chromosomes 11 and 17. Similarly, we detected 463 genetically abnormal embryos by aCGH, among which only 41.9% could be detected by classical fluorescent in situ hybridization (FISH) method. Conclusion: This study not only highlighted the advantages of aCGH over the FISH method in detection of chromosomal abnormalities, but also emphasized the importance of genetic abnormality as an indication for determination of IVF success rate. [ABSTRACT FROM AUTHOR]
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- 2021
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46. Frequency of Sperm Aneuploidy in Oligoasthenoteratozoospermic (OAT) Patients by Comprehensive Chromosome Screening: A Proof of Concept.
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Saei, Parishad, Bazrgar, Masood, Gourabi, Hamid, Kariminejad, Roxana, Eftekhari-Yazdi, Poopak, and Fakhri, Mostafa
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ANEUPLOIDY , *INFERTILITY , *KARYOTYPES , *NUCLEIC acid hybridization , *SPERMATOZOA , *FLUORESCENCE in situ hybridization , *GENETIC testing , *SAMPLE size (Statistics) , *DESCRIPTIVE statistics - Abstract
Background: Embryonic aneuploidy usually results in implantation failure and miscarriage. Considering significantly high frequency of sperm aneuploidy reported in oligoasthenoteratozoospermia (OAT) using fluorescence in situ hybridization (FISH) in limited number of chromosomes and lack of comprehensive chromosome screening (CCS) in OAT, the aim of this study was applying CCS in OAT sperm and comparison of the results with FISH findings. Methods: Five OAT patients with normal blood karyotypes and history of implantation failure were included. The successfully amplified samples, each containing two sperm, were analyzed by array comparative genomic hybridization (aCGH). FISH was utilized mainly depending on the aneuploidies found by aCGH to assess their frequencies in total sperm population. Results: In aCGH for 30 sperm, aneuploidy was found in 66% of samples. Following the study of 4300 sperm by FISH, an average of 55.46% aneuploidy was observed. No pregnancy was resulted with normal partners. Conclusion: Using aCGH, some abnormalities were observed that are not typically considered in sperm FISH studies. Despite small sample size of the comprehensive study, like other similar studies, the frequency of aneuploidies was considerable and similar to FISH. Aneuploidies revealed by aCGH at single sperm resolution were different from sperm population detected by FISH. Considering high frequency of aneuploidy in OATs sperm, preimplantation genetic testing for aneuploidy (PGT-A) can be used for in transfer of chromosomally normal embryos. [ABSTRACT FROM AUTHOR]
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- 2021
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47. Findings from ACGH in patient with psychomotor delay-case report
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Vanja Vidović, Nela Maksimović, Tatjana Damnjanović, Biljana Jekić, Irina Milovac, Milka Grk, and Stojko Vidović
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Array Comparative Genomic Hybridization ,deletion ,duplication ,Genetics ,QH426-470 - Abstract
Initial testing of children with psychomotor delays considers karyotype analysis and metabolic tests. However, introduction of Array Comparative Genomic Hybridization (ACGH) has become the standard method of diagnostics worldwide. ACGH is a highly sensitive method which enables detection of unbalanced chromosomal aberrations and aneuploidies. In this case report, a patient is a sixteen year old girl born to unrelated parents with mild mental retardation and psychomotor delay, hyperacusis, epilepsy, silent nasal speech, clinodactyly of the V finger on left hand, as well as low set ears. Patient had a karyotype interpreted as normal using GTG band analysis. Array CGH was performed using Agilent SurePrint G3 custom CGH+SNP Microarray 8x60K (UCSC, hg19, NCBI Build 37, February,2009). Results were analyzed by CytoGenomics 3.0 Agilent software. Results of aCGH revealed clinically significant duplication of 17q25.1-q25.3 region with the size of~7.96Mb. Within the duplicated region 217 genes are present, of which 36 are described as OMIM morbid. Duplications of similar size are described in DECIPHER date base in patients with psychomotor delay, hyperactivity and neoplasm of CNS. Besides duplication, a ~755kb clinically significant deletion was detected in the 17q25.3 region. Deletion involves 18 genes of which 2 are described as OMIM morbid: TBCD (MIM604649) and ZNF750 (MIM610226). Patient with similar deletion was described in DECIPHER date base with notable psychomotor delay. Based on these results FISH analysis is recommended for both parents in order to determine the possible carrier of inversion in the region of 17qter.
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- 2019
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48. Array Comparative Genomic Hybridization Analysis Reveals Significantly Enriched Pathways in Canine Oral Melanoma
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Ginevra Brocca, Serena Ferraresso, Clarissa Zamboni, Elena M. Martinez-Merlo, Silvia Ferro, Michael H. Goldschmidt, and Massimo Castagnaro
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angiogenesis ,array comparative genomic hybridization ,canine oral melanoma ,comparative oncology ,copy number aberrations ,mucosal melanoma ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Human Mucosal Melanoma (hMM) is an aggressive neoplasm of neuroectodermal origin with distinctive features from the more common cutaneous form of malignant melanoma (cMM). At the molecular level, hMMs are characterized by large chromosomal aberrations rather than single-nucleotide mutations, typically observed in cMM. Given the scarcity of available cases, there have been many attempts to establish a reliable animal model. In pet dogs, Canine Oral Melanoma (COM) is the most common malignant tumor of the oral cavity, sharing clinical and histological aspects with hMM. To improve the knowledge about COM's genomic DNA alterations, in the present work, formalin-fixed, paraffin-embedded (FFPE) samples of COM from different European archives were collected to set up an array Comparative Genomic Hybridization (aCGH) analysis to estimate recurrent Copy Number Aberrations (CNAs). DNA was extracted in parallel from tumor and healthy fractions and 19 specimens were successfully submitted to labeling and competitive hybridization. Data were statistically analyzed through GISTIC2.0 and a pathway-enrichment analysis was performed with ClueGO. Recurrent gained regions were detected, affecting chromosomes CFA 10, 13 and 30, while lost regions involved chromosomes CFA 10, 11, 22, and 30. In particular, CFA 13 showed a whole-chromosome gain in 37% of the samples, while CFA 22 showed a whole-chromosome loss in 25%. A distinctive sigmoidal trend was observed in CFA 10 and 30 in 25 and 30% of the samples, respectively. Comparative analysis revealed that COM and hMM share common chromosomal changes in 32 regions. MAPK- and PI3K-related genes were the most frequently involved, while pathway analysis revealed statistically significant perturbation of cancer-related biological processes such as immune response, drug metabolism, melanocytes homeostasis, and neo-angiogenesis. The latter is a new evidence of a significant involvement of neovascularization-related pathways in COMs and can provide the rationale for future application in anti-cancer targeted therapies.
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- 2019
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49. Array comparative genomic hybridization identifies high level of PI3K/Akt/mTOR pathway alterations in anal cancer recurrences
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Wulfran Cacheux, Petros Tsantoulis, Adrien Briaux, Sophie Vacher, Pascale Mariani, Marion Richard‐Molard, Bruno Buecher, Sophie Richon, Emmanuelle Jeannot, Julien Lazartigues, Etienne Rouleau, Odette Mariani, Elsy El Alam, Jérôme Cros, Sergio Roman‐Roman, Emmanuel Mitry, Elodie Girard, Virginie Dangles‐Marie, Astrid Lièvre, and Ivan Bièche
- Subjects
anal squamous cell carcinoma ,array comparative genomic hybridization ,copy number alterations ,PI3K/Akt/mTOR signaling pathway ,somatic mutations ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Genomic alterations of anal squamous cell carcinoma (ASCC) remain poorly understood due to the rarity of this tumor. Array comparative genomic hybridization and targeted gene sequencing were performed in 49 cases of ASCC. The most frequently altered regions (with a frequency greater than 25%) were 10 deleted regions (2q35, 2q36.3, 3p21.2, 4p16.3, 4p31.21, 7q36.1, 8p23.3, 10q23.2, 11q22.3, and 13q14.11) and 8 gained regions (1p36.33, 1q21.1, 3q26.32, 5p15.33, 8q24.3, 9q34.3, 16p13.3, and 19p13.3). The most frequent minimal regions of deletion (55%) encompassed the 11q22.3 region containing ATM, while the most frequent minimal regions of gain (57%) encompassed the 3q26.32 region containing PIK3CA. Recurrent homozygous deletions were observed for 5 loci (ie, TGFR2 in 4 cases), and recurrent focal amplifications were observed for 8 loci (ie, DDR2 and CCND1 in 3 cases, respectively). Several of the focal amplified genes are targets for specific therapies. Integrated analysis showed that the PI3K/Akt/mTOR signaling pathway was the pathway most extensively affected, particularly in recurrences compared to treatment‐naive tumors (64% vs 30%; P = .017). In patients with ASCC recurrences, poor overall survival (OS) was significantly correlated with a large number of altered regions (P = .024). These findings provide insight into the somatic genomic alterations in ASCC and highlight the key role of the druggable PI3K/Akt/mTOR signaling pathway.
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- 2018
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50. Discovery of molecular subtypes in leiomyosarcoma through integrative molecular profiling
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Beck, AH, Lee, C-H, Witten, DM, Gleason, BC, Edris, B, Espinosa, I, Zhu, S, Li, R, Montgomery, KD, Marinelli, RJ, Tibshirani, R, Hastie, T, Jablons, DM, Rubin, BP, Fletcher, CD, West, RB, and van de Rijn, M
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Biological Sciences ,Biomedical and Clinical Sciences ,Genetics ,Human Genome ,Biotechnology ,Cancer ,2.1 Biological and endogenous factors ,Aetiology ,Biomarkers ,Tumor ,Comparative Genomic Hybridization ,Gene Expression Profiling ,Genomics ,Humans ,Immunohistochemistry ,Leiomyosarcoma ,Prognosis ,Tissue Array Analysis ,sarcoma ,leiomyosarcoma ,integrative genomics ,gene expression profiling ,array comparative genomic hybridization ,tissue microarrays ,Clinical Sciences ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis ,Biochemistry and cell biology ,Oncology and carcinogenesis - Abstract
Leiomyosarcoma (LMS) is a soft tissue tumor with a significant degree of morphologic and molecular heterogeneity. We used integrative molecular profiling to discover and characterize molecular subtypes of LMS. Gene expression profiling was performed on 51 LMS samples. Unsupervised clustering showed three reproducible LMS clusters. Array comparative genomic hybridization (aCGH) was performed on 20 LMS samples and showed that the molecular subtypes defined by gene expression showed distinct genomic changes. Tumors from the 'muscle-enriched' cluster showed significantly increased copy number changes (P=0.04). A majority of the muscle-enriched cases showed loss at 16q24, which contains Fanconi anemia, complementation group A, known to have an important role in DNA repair, and loss at 1p36, which contains PRDM16, of which loss promotes muscle differentiation. Immunohistochemistry (IHC) was performed on LMS tissue microarrays (n=377) for five markers with high levels of messenger RNA in the muscle-enriched cluster (ACTG2, CASQ2, SLMAP, CFL2 and MYLK) and showed significantly correlated expression of the five proteins (all pairwise P
- Published
- 2010
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