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ABSTRACT:
PROVIDER: PRJNA1209716 | ENA |
REPOSITORIES: ENA
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Project description:Heredity is a major risk factor for ovarian cancer, but many families escape detection. Refined diagnosis of ovarian cancers linked to the breast and ovarian cancer (HBOC) syndrome and the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome would allow cancer prevention in high risk families. In order to delineate genetic profiles of hereditary ovarian cancer, we applied genome wide array comparative genomic hybridization to 24 sporadic tumors, 12 HBOC associated tumors (BRCA1 mutations) and eight HNPCC associated tumors (mismatch repair gene mutations). Unsupervised cluster analysis identified two distinctive clusters related to genetic complexity. Most sporadic and HBOC associated tumors had complex genetic profiles with multiple gains and losses with an average of 41% of the genome altered, whereas mismatch repair defective tumors had stable genetic profiles, with an average of 18% of the genome altered. Losses of 4q34, 13q12-q32 and 19p13 were overrepresented in the HBOC subset, gains of chromosomes 17 and 19 characterized the HNPCC tumors and gains of 20q11 were more common in the sporadic tumors. The genetic distinction between HBOC and HNPCC associated ovarian cancer suggests that genetic profiles can be applied for refined classification of hereditary cases and reflects tumor development along different genetic pathways.
2011-04-27 | GSE28850 | GEO
Project description:NGS-based multiple gene panel resequencing in combination with a high resolution CGH-array was used to identify genetic risk factors for hereditary breast and/or ovarian cancer in 237 high risk patients who were previously tested negative for pathogenic BRCA1/2 variants. All patients were screened for pathogenic variants in 94 different cancer predisposing genes. We identified 32 pathogenic variants in 14 different genes (ATM, BLM, BRCA1, CDH1, CHEK2, FANCG, FANCM, FH, HRAS, PALB2, PMS2, PTEN, RAD51C and NBN) in 30 patients (12.7%). Two pathogenic BRCA1 variants that were previously undetected due to less comprehensive and sensitive methods were found. Five pathogenic variants are novel, three of which occur in genes yet unrelated to hereditary breast and/or ovarian cancer (FANCG, FH and HRAS). In our cohort we discovered a remarkably high frequency of truncating variants in FANCM (2.1%), which has recently been suggested as a susceptibility gene for hereditary breast cancer. Two patients of our cohort carried two different pathogenic variants each and ten other patients in whom a pathogenic variant was confirmed also harbored a variant of unknown significance in a breast and ovarian cancer susceptibility gene. We were able to identify pathogenic variants predisposing for tumor formation in 12.3% of BRCA1/2 negative breast and/or ovarian cancer patients.
2018-10-31 | GSE121968 | GEO
Project description:Heredity is a major cause of ovarian cancer. Lynch syndrome is associated with 10-12% risk of ovarian cancer, diagnosis at young age and a predilection for endometrioid and clear cell tumors. Global gene expression profiling applied to 25 Lynch syndrome-associated and 42 sporadic ovarian cancers revealed 335 differentially expressed genes and involvement of the mTOR and the MAPK/ERK pathways. The clear cell tumors had distinct expression profiles with upregulation of HER2 and apoptosis signaling pathways. The distinct expression profiles provide clues relevant for hereditary tumorigenesis and may be relevant for therapeutic strategies and refined diagnostics in ovarian cancer linked to Lynch syndrome. Ovarian cancers linked to Lynch syndrome (n=25) were compared to a matched series of sporadic ovarian cancers (n=42), selected from a population-based consecutive series in which hereditary was excluded based on family history, normal MMR protein staining and lack of mutations in BRCA1 and BRCA2.
2013-10-14 | E-GEOD-37394 | biostudies-arrayexpress
Project description:<p>Cancer risk shows clear heritability, but the inherited genetic factors remain largely unknown. This project will seek to identify new genes in which mutations confer hereditary risk for early onset breast cancer, with important implications for both biological understanding and clinical prediction and prevention. Identifying cancer predisposing mutations can provide new biological insights and significantly impact important clinical decision making regarding treatment, surveillance and preventive approaches. Examples include the BRCA1 breast cancer susceptibility gene, which affects treatment decisions (surgical management), surveillance (frequent breast MRI) and prevention (oophorectory for prevention of ovarian cancer). Hereditary early onset breast cancer patients commonly present to Cancer Genetics clinics, but the majority of these patients do not have identifiable mutations in known candidate genes. Here, we will perform whole exome sequencing to discover novel cancer susceptibility genes. The patients have been recruited from Memorial Sloan Kettering Cancer Center (PIs Kenneth Offit and Zsofia Stadler) and Massachusetts General Hospital (PI Daniel Haber).</p> <p>All exome sequencing was performed at the Broad Institute of Harvard and MIT; samples sequence capture was performed using Agilent SureSelect Human All Exon Kit v2 and sequencing was performed on an Illumina HiSeq 2000 or 2500.</p>
| phs000822 | dbGaP
Project description:Background:This study was a hypothesis generating exploration of genomic data collected at diagnosis for 19 patients, who later participated in a clinical trial. BRCA1/2 germline mutation related hereditary cancers are candidates for new immune therapeutic interventions. However, contrary to what is expected of tumors with compromised DNA repair, a prominent tumor mutation burden (TMB) in hereditary breast and ovarian cancers in this cohort, was not correlated with high global immune activity in their microenvironments. More information is needed about the relationship between genomic instability, phenotypes and immune microenvironments of BRCA1/2 related hereditary tumors in order to find appropriate markers of immune activity and the most effective anticancer immune strategies. Methods:Mining and statistical analyses of the original DNA and RNA sequencing data and data available from The Cancer Genome Atlas (TCGA) were performed using the R computing environment. To interpret the data, we have used published literature and web available resources such as Gene Ontology Tools, The Cancer immunome Atlas (TCIA) and the Cancer Research Institute iAtlas. Results: We found that BRCA1/2 germline related breast and ovarian cancers do not represent a unique phenotypic identity, but that they express a range of phenotypes similar to sporadic cancers. Importantly, BRCA2 germline mutation related breast tumors have a different profile of genomic instability compared to those related to BRCA1. However, all breast and ovarian BRCA1/2 related tumors are characterized by high homologous recombination deficiency (HRD) and low aneuploidy. Interestingly, all sporadic high grade serous ovarian cancers (HGSOC) and most of the subtypes of triple negative breast cancers (TNBC), but not other types of breast cancer, also express a high degree of HRD. Conclusion: : Tumor mutation burdon (TMB) is not associated with the magnitude of the immune response in hereditary BRCA1/2 related breast and ovarian cancers or in sporadic TNBC and sporadic HGSOC. Hereditary tumors express phenotypes as heterogenous as sporadic tumors with various degree of “BRCAness” and various characteristics of the immune microenvironments. The subtyping criteria developed for sporadic tumors can be applied for the classification of hereditary tumors and possibly also characterization of their immune microenvironment. A high HRD score may be a good candidate biomarker for response to platinum, and potentially PARP-inhibition.
2019-11-28 | GSE141142 | GEO
Project description:This study was conducted in order to characterize genomic instability level and pattern in hereditary and sporadic ovarian tumours and define common and/or distinct events occurring in the genesis and evolution of these neoplasms. Overall study comprises 68 epithelial ovarian cancer samples (53 familial and 15 sporadic cases) on high resolution 4x180K Agilent platform.
2012-10-02 | E-GEOD-41253 | biostudies-arrayexpress
Project description:RNA sequencing and whole-exome sequencing data were obtained from 30 platinum-resistant recurrent ovarian cancer samples.
2023-05-01 | GSE230541 | GEO
Project description:RNA sequencing and whole-exome sequencing data were obtained from 42 advanced-stage epithelial ovarian cancer (EOC) samples.
2025-01-15 | GSE284400 | GEO
Project description:The diversity and heterogeneity within high-grade serous ovarian cancer (HGSC) is not well understood. Comprehensive molecular analyses were performed including high-pass whole-genome sequencing, targeted deep DNA sequencing, RNA sequencing, reverse-phase protein arrays, mass spectrometry-based proteomics and phosphoproteomics, and immune profiling on primary and metastatic sites from highly clinically annotated HGSC samples. Samples were obtained pre-treatment based on a laparoscopic triage algorithm from patients who underwent R0 tumor debulking or received neoadjuvant chemotherapy (NACT) with excellent or poor response.
2020-05-27 | PXD014980 | Pride
Project description:To determine microRNA expression in chemoresistant ovarian cancer, we have employed whole microRNA microarray expression profiling as a discovery platform to identify genes with the potential to distinguish recurrent ovarian cancer. 8 recurrent ovarian cancer tissue and 8 primary ovarian cancer tissue and 4 normal ovarian tissue was used to identify miRNA profiling.
2017-06-01 | GSE83693 | GEO