Genomic consequences of aberrant DNA repair mechanisms stratify ovarian cancer histotypes

Sohrab Shah, David Huntsman and colleagues report the genomic analysis of 133 ovarian cancers spanning different subtypes. They identify seven subgroups using point mutation and structural variation signatures and use these genomic features to stratify ovarian cancers both between and within histoty...

Celý popis

Uložené v:

Podrobná bibliografia
Vydané v:	Nature genetics Ročník 49; číslo 6; s. 856 - 865
Hlavní autori:	Wang, Yi Kan, Bashashati, Ali, Anglesio, Michael S, Cochrane, Dawn R, Grewal, Diljot S, Ha, Gavin, McPherson, Andrew, Horlings, Hugo M, Senz, Janine, Prentice, Leah M, Karnezis, Anthony N, Lai, Daniel, Aniba, Mohamed R, Zhang, Allen W, Shumansky, Karey, Siu, Celia, Wan, Adrian, McConechy, Melissa K, Li-Chang, Hector, Tone, Alicia, Provencher, Diane, de Ladurantaye, Manon, Fleury, Hubert, Okamoto, Aikou, Yanagida, Satoshi, Yanaihara, Nozomu, Saito, Misato, Mungall, Andrew J, Moore, Richard, Marra, Marco A, Gilks, C Blake, Mes-Masson, Anne-Marie, McAlpine, Jessica N, Aparicio, Samuel, Huntsman, David G, Shah, Sohrab P
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	New York Nature Publishing Group US 01.06.2017 Nature Publishing Group
Predmet:	45/77 49/39 631/114/2785 631/67/1517/1709 Aberration Age Agriculture Animal Genetics and Genomics Biomarkers Biomedicine BRCA1 protein BRCA1 Protein - genetics BRCA2 protein BRCA2 Protein - genetics Breast cancer Cancer Cancer Research Care and treatment Clustering Colleges & universities Deamination Deoxyribonucleic acid Development and progression DNA DNA methylation DNA repair DNA Repair - genetics Endometriosis - complications Endometriosis - genetics Female Gene expression Gene Expression Regulation, Neoplastic Gene Function Genetic aspects Genetic testing Genome, Human Genomes Gynecology Health aspects Human Genetics Humans Inversions Medical screening Medicine Microsatellite instability Mutation Obstetrics Oncology Ovarian cancer Ovarian Neoplasms - drug therapy Ovarian Neoplasms - genetics Ovarian Neoplasms - mortality Ovarian Neoplasms - pathology Point mutation Prognosis Repair Signatures Stability Strata Stratigraphy Subgroups Survival Trends Tumors Canada
ISSN:	1061-4036, 1546-1718, 1546-1718
On-line prístup:	Získať plný text
Tagy:	Pridať tag Žiadne tagy, Buďte prvý, kto otaguje tento záznam!

Popis
Shrnutí:	Sohrab Shah, David Huntsman and colleagues report the genomic analysis of 133 ovarian cancers spanning different subtypes. They identify seven subgroups using point mutation and structural variation signatures and use these genomic features to stratify ovarian cancers both between and within histotypes. We studied the whole-genome point mutation and structural variation patterns of 133 tumors (59 high-grade serous (HGSC), 35 clear cell (CCOC), 29 endometrioid (ENOC), and 10 adult granulosa cell (GCT)) as a substrate for class discovery in ovarian cancer. Ab initio clustering of integrated point mutation and structural variation signatures identified seven subgroups both between and within histotypes. Prevalence of foldback inversions identified a prognostically significant HGSC group associated with inferior survival. This finding was recapitulated in two independent cohorts ( n = 576 cases), transcending BRCA1 and BRCA2 mutation and gene expression features of HGSC. CCOC cancers grouped according to APOBEC deamination (26%) and age-related mutational signatures (40%). ENOCs were divided by cases with microsatellite instability (28%), with a distinct mismatch-repair mutation signature. Taken together, our work establishes the potency of the somatic genome, reflective of diverse DNA repair deficiencies, to stratify ovarian cancers into distinct biological strata within the major histotypes.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	1061-4036 1546-1718 1546-1718
DOI:	10.1038/ng.3849