9 results on '"Limon, Janusz"'
Search Results
2. HER2 Amplification Has no Prognostic Value in Sporadic and Hereditary Ovarian Tumours
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Brożek Izabela, Kardaś Iwona, Ochman Karolina, Dębniak Jarosław, Stukan Maciej, Ratajska Magdalena, Morzuch Lucyna, Emerich Janusz, and Limon Janusz
- Subjects
HER2 ,ovarian cancer ,BRCA ,outcome ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Genetics ,QH426-470 - Abstract
Abstract Whereas HER2 amplification is a well-known phenomenon in breast tumours, its frequency and clinical importance in ovarian cancer have not been established. The aim of the study was to compare the frequency of HER2 amplification in hereditary (BRCA-positive) and sporadic (BRCA-negative) ovarian tumours and to estimate the association of this gene alteration on clinical outcome in ovarian cancer patients. We analysed HER2 amplification in 53 ovarian tumours: 20 from mutation carriers (18 in BRCA1 and 2 in BRCA2 gene) and 33 from non-carriers. Fluorescence in situ hybridization for HER2 was performed on 'touch' slides from frozen tumour samples or formalin-fixed, paraffin-embedded tissue. Our results indicate that high amplification (HER2: centromere ratio>5) is an infrequent phenomenon in ovarian tumours (6/53 cases). It occurs in both hereditary (4/20) and sporadic (2/33) tumours and no difference in the frequency of HER2 amplification exists between these groups. There is no significant difference in the clinical outcome of patients with HER2 amplified and non-amplified tumours (p = 0.3). Our results suggest a different biological role of HER2 amplification in ovarian and breast cancer.
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- 2006
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3. Cancer predisposing BARD1 mutations in breast–ovarian cancer families
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Ratajska, Magdalena, Antoszewska, Ewelina, Piskorz, Anna, Brozek, Izabela, Borg, Åke, Kusmierek, Hanna, Biernat, Wojciech, and Limon, Janusz
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- 2012
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4. Bayesian multilevel model of micro RNA levels in ovarian-cancer and healthy subjects.
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Wiczling, Paweł, Daghir-Wojtkowiak, Emilia, Kaliszan, Roman, Markuszewski, Michał Jan, Limon, Janusz, Koczkowska, Magdalena, Stukan, Maciej, Kuźniacka, Alina, and Ratajska, Magdalena
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MICRORNA ,MULTILEVEL models ,NON-coding RNA ,RECEIVER operating characteristic curves ,OVARIAN cancer - Abstract
In transcriptomics, micro RNAs (miRNAs) has gained much interest especially as potential disease indicators. However, apart from holding a great promise related to their clinical application, a lot of inconsistent results have been published. Our aim was to compare the miRNA expression levels in ovarian cancer and healthy subjects using the Bayesian multilevel model and to assess their potential usefulness in diagnosis. We have analyzed a case-control observational data on expression profiling of 49 preselected miRNA-based ovarian cancer indicators in 119 controls and 59 patients. A Bayesian multilevel model was used to characterize the effect of disease on miRNA levels controlling for differences in age and body weight. The difference between the miRNA level and health status of the patient on the scale of the data variability were discussed in the context of their potential usefulness in diagnosis. Additionally, the cross-validated area under the ROC curve (AUC) was used to assess the expected out-of-sample discrimination index of a different sets of miRNAs. The proposed model allowed us to describe the set of miRNA levels in patients and controls. Three highly correlated miRNAs: miR-101-3p, miR-142-5p, miR-148a-3p rank the highest with almost identical effect sizes that ranges from 0.45 to 1.0. For those miRNAs the credible interval for AUC ranged from 0.63 to 0.67 indicating their limited discrimination potential. A little benefit in adding information from other miRNAs was observed. There were several miRNAs in the dataset (miR-604, hsa-miR-221-5p) for which inferences were uncertain. For those miRNAs more experimental effort is needed to fully assess their effect in the context of new hits discovery and usefulness as disease indicators. The proposed multilevel Bayesian model can be used to characterize the panel of miRNA profile and to assess the difference in expression levels between healthy and cancer individuals. [ABSTRACT FROM AUTHOR]
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- 2019
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5. Detection of somatic BRCA1/2 mutations in ovarian cancer - next-generation sequencing analysis of 100 cases.
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Koczkowska, Magdalena, Zuk, Monika, Gorczynski, Adam, Ratajska, Magdalena, Lewandowska, Marzena, Biernat, Wojciech, Limon, Janusz, and Wasag, Bartosz
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CANCER genetics ,OVARIAN cancer ,BRCA genes ,SOMATIC mutation ,OVARIAN cancer diagnosis ,GERM cells ,DNA damage - Abstract
The overall prevalence of germline BRCA1/2 mutations is estimated between 11% and 15% of all ovarian cancers. Individuals with germline BRCA1/2 alterations treated with the PARP1 inhibitors ( iPARP1) tend to respond better than patients with wild-type BRCA1/2. Additionally, also somatic BRCA1/2 alterations induce the sensitivity to iPARP1. Therefore, the detection of both germline and somatic BRCA1/2 mutations is required for effective iPARP1 treatment. The aim of this study was to identify the frequency and spectrum of germline and somatic BRCA1/2 alterations in a group of Polish patients with ovarian serous carcinoma. In total, 100 formalin-fixed paraffin-embedded ( FFPE) ovarian serous carcinoma tissues were enrolled to the study. Mutational analysis of BRCA1/ 2 genes was performed by using next-generation sequencing. The presence of pathogenic variants was confirmed by Sanger sequencing. In addition, to confirm the germline or somatic status of the mutation, the nonneoplastic tissue was analyzed by bidirectional Sanger sequencing. In total, 27 (28% of patient samples) mutations (20 in BRCA1 and 7 in BRCA2) were identified. For 22 of 27 patients, nonneoplastic cells were available and sequencing revealed the somatic character of two BRCA1 (2/16; 12.5%) and two BRCA2 (2/6; 33%) mutations. Notably, we identified six novel frameshift or nonsense BRCA1/2 mutations. The heterogeneity of the detected mutations confirms the necessity of simultaneous analysis of BRCA1/ 2 genes in all patients diagnosed with serous ovarian carcinoma. Moreover, the use of tumor tissue for mutational analysis allowed the detection of both somatic and germline BRCA1/2 mutations. [ABSTRACT FROM AUTHOR]
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- 2016
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6. A novel splicing mutation in the SLC9A3R1 gene in tumors from ovarian cancer patients.
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KREIMANN, ERICA LORENA, RATAJSKA, MAGDALENA, KUZNIACKA, ALINA, DEMACOPULO, BRENDA, STUKAN, MACIEJ, and LIMON, JANUSZ
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CANCER genetics ,OVARIAN cancer ,OVARIAN cancer treatment ,GENETIC engineering ,SODIUM-hydrogen antiporter ,OVARIAN cancer diagnosis ,CANCER patients - Abstract
The aim of the present study was to investigate novel molecular markers that could improve the diagnosis of ovarian cancer patients or be of predictive value. The sequence of the sodium-hydrogen antiporter 3 regulator 1 (SLC9A3R1) gene that codes for the PDZ2 motif of the Na+/H+ exchanger regulatory factor 1 (NHERF1) protein was analyzed. Changes in migration and cell transformation, and alterations of growth factor signaling pathways have been described in cells lacking endogenous NHERF1 or expressing an isoform lacking the function of the PDZ2 domain. Exons 2 and 3, together with flanking intronic sequences of the SLC9A3R1 gene, were amplified and bi-directionally sequenced in 31 primary tumor samples from epithelial ovarian cancer patients. In total, 3 different previously undescribed mutations were detected in 8 out of 31 serous adenocarcinoma tumor samples (25.8%). Bioinformatics analysis predicted a significant effect in the splicing process as a result of the mutations that could disrupt the NHERF1 PDZ2 domain. Point mutations in consensus splicing recognition are a major cause of the splicing defects that are found in several diseases, including cancer. It has previously been shown that a lack of exon 2 and disruption of the PDZ2 domain contribute to cell transformation and leads to modifications in the physiological regulation of the conformational state of NHERF1. Further studies in bigger groups of ovarian cancer patients will determine the importance of this mutation in disease progression and patient survival. [ABSTRACT FROM AUTHOR]
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- 2015
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7. Spectrum and Prevalence of Pathogenic Variants in Ovarian Cancer Susceptibility Genes in a Group of 333 Patients.
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Koczkowska, Magdalena, Krawczynska, Natalia, Stukan, Maciej, Kuzniacka, Alina, Brozek, Izabela, Sniadecki, Marcin, Debniak, Jaroslaw, Wydra, Dariusz, Biernat, Wojciech, Kozlowski, Piotr, Limon, Janusz, Wasag, Bartosz, and Ratajska, Magdalena
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OVARIAN tumors ,DISEASE susceptibility ,GENETIC polymorphisms ,ONCOGENES ,RISK assessment ,SPECTRUM analysis ,DISEASE prevalence ,GENETICS - Abstract
Constitutional loss-of-function pathogenic variants in the tumor suppressor genes BRCA1 and BRCA2 are widely associated with an elevated risk of ovarian cancer (OC). As only ~15% of OC individuals carry the BRCA1/2 pathogenic variants, the identification of other potential OC-susceptibility genes is of great clinical importance. Here, we established the prevalence and spectrum of the germline pathogenic variants in the BRCA1/2 and 23 other cancer-related genes in a large Polish population of 333 unselected OC cases. Approximately 21% of cases (71/333) carried the BRCA1/2 pathogenic or likely pathogenic variants, with c.5266dup (p.Gln1756Profs*74) and c.3700_3704del (p.Val1234Glnfs*8) being the most prevalent. Additionally, ~6% of women (20/333) were carriers of the pathogenic or likely pathogenic variants in other cancer-related genes, with NBN and CHEK2 reported as the most frequently mutated, accounting for 1.8% (6/333) and 1.2% (4/333) of cases, respectively. We also found ten pathogenic or likely pathogenic variants in other genes: 1/333 in APC, 1/333 in ATM, 2/333 in BLM, 1/333 in BRIP1, 1/333 in MRE11A, 2/333 in PALB2, 1/333 in RAD50, and 1/333 in RAD51C, accounting for 50% of all detected variants in moderate- and low-penetrant genes. Our findings confirmed the presence of the additional OC-associated genes in the Polish population that may improve the personalized risk assessment of these individuals. [ABSTRACT FROM AUTHOR]
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- 2018
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8. Analysis of large mutations in BARD1 in patients with breast and/or ovarian cancer: the Polish population as an example.
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Klonowska, Katarzyna, Ratajska, Magdalena, Czubak, Karol, Kuzniacka, Alina, Brozek, Izabela, Koczkowska, Magdalena, Sniadecki, Marcin, Debniak, Jaroslaw, Wydra, Dariusz, Balut, Magdalena, Stukan, Maciej, Zmienko, Agnieszka, Nowakowska, Beata, Irminger-Finger, Irmgard, Limon, Janusz, and Kozlowski, Piotr
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BREAST cancer ,GENETIC mutation ,OVARIAN cancer ,GENETICS ,DISEASE susceptibility - Abstract
Only approximately 50% of all familial breast cancers can be explained by known genetic factors, including mutations in BRCA1 and BRCA2. One of the most extensively studied candidates for breast and/or ovarian cancer susceptibility is BARD1. Although it was suggested that large mutations may contribute substantially to the deleterious variants of BARD1, no systematic study of the large mutations in BARD1 has been performed. To further elucidate the role of large mutations in BARD1, we designed a multiplex ligation-dependent probe amplification (MLPA) assay and performed an analysis of 504 women with a familial breast and/or ovarian cancer and 313 patients with ovarian cancer. The investigation did not reveal any large mutations in the BARD1 gene. Although the analysis was not focused on identification of small mutations, we detected seven deleterious or potentially deleterious point mutations, which contribute substantially to the total number of BARD1 mutations detected so far. In conclusion, although we cannot exclude the presence of large mutations in BARD1, our study indicates that such mutations do not contribute substantially to the risk of breast and/or ovarian cancer. However, it has to be noted that our results may be specific to the Polish population. [ABSTRACT FROM AUTHOR]
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- 2015
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9. High frequency of BRCA1/2 germline mutations in consecutive ovarian cancer patients in Poland
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Brozek, Izabela, Ochman, Karolina, Debniak, Jarosław, Morzuch, Lucyna, Ratajska, Magdalena, Stepnowska, Magdalena, Stukan, Maciej, Emerich, Janusz, and Limon, Janusz
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CANCER patients , *CANCER in women , *GYNECOLOGIC cancer , *DISEASES in women - Abstract
Abstract: Background. : We estimated the prevalence of BRCA1/2 germline mutations in consecutive ovarian cancers and correlated the mutation status with clinicopathological features. Methods. : 151 consecutive primary ovarian cancer patients were screened for BRCA1/2 germline mutations. Results. : We identified BRCA1/2 germline mutations in 21 (13.9%) patients. Seventeen (81%) of carriers have BRCA1 and four (19%) have BRCA2 mutation. BRCA1/2 carriers have a distinctly longer overall survival than sporadic cases (log-rank, p =0.014). Conclusions. : The relatively high proportion of BRCA1/2 carriers among unselected ovarian cancer patients indicates the necessity of searching for recurrent BRCA mutations in each case of ovarian carcinoma. This routine screen should be widened to include denaturing high performance liquid chromatography (DHPLC) analysis of both exons 11 of BRCA1 and BRCA2 genes in women with positive family history. [Copyright &y& Elsevier]
- Published
- 2008
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