Scientific Publications

Integrated genomic characterization of endometrial carcinoma.

Publication TypeJournal Article
AuthorsCancer Genome Atlas Research, Network, Genome sequencing centres: Broad Institute, Getz G., Gabriel SB, Cibulskis K., Lander E., Sivachenko A., Sougnez C., Lawrence M., Washington University in St Louis, Kandoth C., Dooling D., Fulton R., Fulton L., Kalicki-Veizer J., McLellan MD, O'Laughlin M., Schmidt H., Wilson RK, Ye K., et al.
AbstractWe performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine serous tumours and ∼25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, and frequent TP53 mutations. Most endometrioid tumours had few copy number alterations or TP53 mutations, but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A and KRAS and novel mutations in the SWI/SNF chromatin remodelling complex gene ARID5B. A subset of endometrioid tumours that we identified had a markedly increased transversion mutation frequency and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours.
Year of Publication2013
JournalNature
Volume497
Issue7447
Pages67-73
Date Published (YYYY/MM/DD)2013/05/02
ISSN Number0028-0836
DOI10.1038/nature12113
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/23636398?dopt=Abstract