Integrated genomic characterization of endometrial carcinoma.

TitleIntegrated genomic characterization of endometrial carcinoma.
Publication TypeJournal Article
Year of Publication2013
AuthorsKandoth, C, Schultz, N, Cherniack, AD, Akbani, R, Liu, Y, Shen, H, A Robertson, G, Pashtan, I, Shen, R, Benz, CC, Yau, C, Laird, PW, Ding, L, Zhang, W, Mills, GB, Kucherlapati, R, Mardis, ER, Levine, DA
Corporate Authors
JournalNature
Volume497
Issue7447
Pagination67-73
Date Published2013 May 2
ISSN1476-4687
KeywordsBreast Neoplasms, Chromosome Aberrations, DNA Copy Number Variations, DNA Mutational Analysis, DNA Polymerase II, DNA-Binding Proteins, Endometrial Neoplasms, Exome, Female, Gene Expression Regulation, Neoplastic, Genome, Human, Genomics, Humans, Ovarian Neoplasms, Signal Transduction, Transcription Factors
Abstract

We 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.

DOI10.1038/nature12113
Alternate JournalNature
PubMed ID23636398
PubMed Central IDPMC3704730
Grant List5U24CA143799-04 / CA / NCI NIH HHS / United States
5U24CA143835-04 / CA / NCI NIH HHS / United States
5U24CA143840-04 / CA / NCI NIH HHS / United States
5U24CA143843-04 / CA / NCI NIH HHS / United States
5U24CA143845-04 / CA / NCI NIH HHS / United States
5U24CA143848-04 / CA / NCI NIH HHS / United States
5U24CA143858-04 / CA / NCI NIH HHS / United States
5U24CA143866-04 / CA / NCI NIH HHS / United States
5U24CA143867-04 / CA / NCI NIH HHS / United States
5U24CA143882-04 / CA / NCI NIH HHS / United States
5U24CA143883-04 / CA / NCI NIH HHS / United States
5U24CA144025-04 / CA / NCI NIH HHS / United States
P30 CA008748 / CA / NCI NIH HHS / United States
P30 CA016086 / CA / NCI NIH HHS / United States
P30 CA016672 / CA / NCI NIH HHS / United States
P50 CA098258 / CA / NCI NIH HHS / United States
U24 CA143799 / CA / NCI NIH HHS / United States
U24 CA143835 / CA / NCI NIH HHS / United States
U24 CA143840 / CA / NCI NIH HHS / United States
U24 CA143843 / CA / NCI NIH HHS / United States
U24 CA143845 / CA / NCI NIH HHS / United States
U24 CA143848 / CA / NCI NIH HHS / United States
U24 CA143858 / CA / NCI NIH HHS / United States
U24 CA143866 / CA / NCI NIH HHS / United States
U24 CA143867 / CA / NCI NIH HHS / United States
U24 CA143882 / CA / NCI NIH HHS / United States
U24 CA143883 / CA / NCI NIH HHS / United States
U24 CA144025 / CA / NCI NIH HHS / United States
U54 HG003067 / HG / NHGRI NIH HHS / United States
U54 HG003079 / HG / NHGRI NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
U54HG003067-11 / HG / NHGRI NIH HHS / United States
U54HG003079-10 / HG / NHGRI NIH HHS / United States
U54HG003273-10 / HG / NHGRI NIH HHS / United States