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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]

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]

A patient with a rare interstitial deletion of chromosomal band 2q33.2q33.3 is described. The clinical features resembled the 2q33.1 microdeletion syndrome (Glass syndrome), including mental retardation, facial dysmorphism, high-arched narrow palate, growth deficiency, and speech delay. The chromosomal aberration was characterized by whole genome BAC aCGH. A comparison of the current patient and Glass syndrome features revealed that this case displayed a relatively mild phenotype. Overall, it is suggested that the deleted region of 2q33 causative for Glass syndrome may be larger than initially suggested. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Cleft lip with or without cleft palate is one of the most common birth defects of unknown etiology. A fraction of its genetic causes is attributable to copy number variations detected by array comparative genomic hybridization. The value of array comparative genomic hybridization screening as a first-tier test in the newborn population with multiple congenital anomalies has now been accepted. Due to unspecific clinical picture at this age, it can also be applied to neonates with isolated anomalies. Our purpose was to assess utility of array comparative genomic hybridization in the population of newborns with isolated cleft lip and palate. We conducted the study in a group of 52 Polish newborns with apparently isolated cleft lip and palate. In the study group, we found 8 rearrangements. Of these, 2 de novo events have been noted that potentially explain the phenotype. In addition, 2 novel candidate genes for cleft lip and palate, CHN2 and CDH19, are suggested. Given the high number of inherited potentially benign changes, we question the clinical utility of array comparative genomic hybridization in the newborn population with isolated cleft lip and palate, at the same time pointing to the need of skilled professional's clinical assessment at a later age. However, the value of this technology in searching for the cause of isolated anomalies cannot be underestimated. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

We provide a detailed clinical and molecular analysis of 2 patients with de novo interstitial duplications at 2p14-p16.1 and 2p16.1-p22.1. The 10.13-Mb duplication of chromosome 2p14-p16.1 was identified in a 9-year-old boy with mental retardation, behavioral problems (hyperactivity, hyperphagia, and subsequent vomiting), recurrent respiratory tract infections, macrocephaly, epilepsy, and dysmorphic features. The 17.49-Mb duplication of 2p16.1-p22.1 was found in a 17-year-old girl with moderate mental retardation, behavioral and emotional problems, anxiety, and facial dysmorphic features. Very few cases of de novo interstitial duplication of 2p14-p22.1 are reported in the literature, with the great majority of them lacking a detailed molecular analysis. The abnormal phenotype of these cases is caused by mechanisms such as the overdose of a duplicated gene (or genes), the disruption of a gene or its regulatory sequence by the breakpoints of duplication, or by an excess of genetic material which may disorganize chromatin conformation affecting distant gene expression. The clinical and molecular analysis of these 2 rare de novo interstitial duplications provides useful information which is extremely valuable for clinical evaluation at the prenatal and postnatal level and for the molecular understanding of the underlying mechanisms of human diseases. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

This is the first case of 2q32 microdeletion syndrome diagnosed prenatally and followed throughout the pregnancy. The pregnancy was complicated by fetal club feet, ventriculomegaly, intrauterine growth retardation and polyhydramnios. This is a unique and highly complicated prenatal diagnosis case of a de novo complex chromosomal rearrangement involving chromosomes 2, 5 and 7 with 15 breaks and multiple interstitial 2q deletions, resulting in the 2q32 microdeletion syndrome. The delineation of the karyotype in this case and origin of the pathology required the use of multiple genetic technologies including conventional cytogenetics, fluorescence in situ hybridization, single-nucleotide polymorphism array and array comparative genomic hybridization. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

We report on 2 similarly affected cousins with a compound imbalance resulting from a familial t(5;9)(q34;p23) and entailing both an ∼17-Mb 5q terminal duplication and an ∼12-Mb 9p terminal deletion as determined by G-banding, subtelomere FISH, and aCGH. The proband's karyotype was 46,XX,der(9)t(5;9)(q34;p23)mat.ish der(9)t(5;9)(q34;p23)(9pter-,5qter+).arr 5q34q35(163,328,000-180,629,000)×3, 9p24p23(194,000-12,664,000)×1. Her cousin had the same unbalanced karyotype inherited from his father. The clinical phenotype mainly consists of a distinct craniofacial dysmorphism featuring microcephaly, flat facies, down slanting palpebral fissures, small flat nose, long philtrum, and small mouth with thin upper lip. Additional remarkable findings were craniosynostosis of several sutures, craniolacunia and preaxial polydactyly in the proband and hypothyroidism in both subjects. The observed clinical constellation generally fits the phenotypic spectrum of the 5q distal duplication syndrome (known also as Hunter-McAlpine syndrome), except for the thyroid insufficiency which can likely be ascribed to the concurrent 9p deletion, as at least 4 other 9pter monosomic patients without chromosome 5 involvement had this hormonal disorder. The present observation further confirms the etiology of the HMS phenotype from gain of the 5q35→qter region, expands the clinical pictures of partial trisomy 5q and monosomy 9p, and provides a comprehensive list of 160 patients with 5q distal duplication. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

A 3-year-old girl with an inherited translocation of 4q onto the long arm of chromosome 10 is reported as a case of ‘pure’ partial trisomy 4q. The main clinical features of the patient included moderate mental retardation (IQ = 40), growth retardation, language handicap, right hand preaxial hexadactyly, and abnormal electroencephalogram. Conventional cytogenetic analysis showed partial trisomy 4q25→qter was present in the patient, both patient’s father and grandmother were apparently balanced translocation t(4;10) (q25;q26) carriers, which suggests that the partial trisomy 4q25→qter in the patient results from unbalanced segregation of the father’s translocation. The extension of the trisomic 4q region was redefined by array comparative genomic hybridization (array-CGH), the breakpoint on chromosome 4 was located at 4q26 (between 115,596,658 bp and 118,785,802 bp from the telomere of 4p), and an ∼0.54-Mb microdeletion del(10)(q26.3) (between 134,750,859 bp and 135,286,223 bp from the telomere of 10p) was identified. FISH and RT-qPCR confirmed that del(10)(q26.3) was also present in both father and grandmother, which suggests that their translocations are actually unbalanced and the patient’s abnormal phenotypes may only ascribe to partial trisomy 4q26→q35.2. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives: Etiologic diagnosis of multiple congenital abnormalities (MCAs) is often lacking. Large chromosome abnormalities can be detected by conventional cytogenetic methods, but more subtle chromosome micro-rearrangements and/or de novo abnormalities require multi-FISH analysis, which is hampered by the amount of material available in prenatal testing. Methods: We used the comparative genomic hybridization (CGH) array, Genosensor™ Array 300, to screen for classic microdeletion syndromes and subtelomeric rearrangements in 39 consecutive fetuses with MCAs, after termination of pregnancy, in a prospective study. Thirty-seven of them had a normal karyotype, and two had a de novo unbalanced karyotype that could not be characterized with conventional cytogenetic methods. Results: Two de novo unbalanced karyotypes were characterized by array CGH, and four additional abnormalities were diagnosed: an unbalanced inherited cryptic translocation, a deletion in band 22q11.2, a 1p36 deletion, and a 6p12.1–21.2 duplication. Conclusion: Chromosomal imbalances were therefore detected and/or characterized in 6 of 39 (15.4%) fetuses, indicating the value of routine array CGH in cases of MCAs and in uncharacterized chromosome rearrangements. Extension to all prenatal diagnoses may be warranted when copy number variation is identified and all FISH probes are commercially available. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Chemotherapy resistance remains a major obstacle to successful treatment of ovarian cancer patients. Therefore, increased knowledge of underlying mechanisms and identification of predictive factors are of great importance. Standard treatment for ovarian carcinoma is surgery followed by platinum-based chemotherapy. In this study, we aimed to search for genes or genomic regions involved in platinum resistance in ovarian carcinoma. Array-based comparative genomic hybridization (CGH) was used to identify genetic alterations in 32 early-stage epithelial ovarian carcinomas homogeneously treated with single-agent carboplatin. The arrays contain 33,370 bacterial artificial chromosome (BAC) clones and form a contiguous and tiling coverage of the human genome with an average resolution of ∼100 kb. We found certain genetic changes associated with carboplatin response. Gains in 1q25.1–q41 were significantly more frequent in carboplatin-resistant tumours. In this region, we further detected two smallest regions of overlap (SRO) at 1q25.2 and 1q32.2 (∼690 and ∼830 kb in size, respectively). Interestingly, we found some regions that were lost exclusively in the sensitive tumours 17q24.1, Xq21.33–q22.1, and 6 regions in 15q. We also detected genetic differences with regard to histologic subtype. Gain in 8q was found highly associated with serous and clear cell subtypes, and an SRO was identified at 8q24.22–q24.23. The genomic regions found altered in this study confirm some of our previous metaphase CGH results. The alteration found in chromosome arm 1q was verified and specified, and is therefore of great interest as a candidate for predictive markers. Identifying predictive markers of chemosensitive and chemoresistant disease would greatly help in the choice of chemotherapy in the clinic, and thus improve treatment of women with ovarian cancer. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives: To explore the advantages and limitations of comparative genomic hybridization to BAC arrays (array CGH) for prenatal diagnosis of a fetus with anomalies and a chromosome abnormality. Methods: We used karyotype analysis, FISH and array CGH to investigate an unbalanced chromosome rearrangement. Results: We report a case of a fetus with ultrasound anomalies at 11 weeks’ gestation and an unbalanced chromosome translocation [46,XX,der(13)t(2;13)(p25.1;q32)pat]. Initially, a chromosome 13 deletion was reported from G-banded chromosome analysis and 13q subtelomere FISH. The involvement of chromosome 2 was determined after a balanced translocation was identified in the father, 46,XY,t(2;13)(p25.1;q32). Array CGH confirmed the fetal abnormality as partial trisomy of the short arm chromosome 2 and partial monosomy of the long arm of chromosome 13. The abnormalities identified by ultrasound studies and autopsy appear to be most consistent with 13q deletion syndrome. Conclusions: Array CGH successfully identified a subtle unbalanced chromosome complement in a fetus with multiple ultrasound anomalies. If array CGH had been performed along with the fetal karyotype, the cryptic partial trisomy 2 could have been identified in a more timely manner to assist in the prenatal counseling of this family. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]