Integrated genomic characterization of endometrial carcinoma.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Cancer Genome Atlas Research Network, ; Kandoth, C; Schultz, N; Cherniack, AD; Akbani, R; Liu, Y; Shen, H; Robertson, AG; Pashtan, I; Shen, R; Benz, CC; Yau, C; Laird, PW; Ding, L; Zhang, W; Mills, GB; Kucherlapati, R; Mardis, ER; Levine, DA

Published Date

  • May 2, 2013

Published In

Volume / Issue

  • 497 / 7447

Start / End Page

  • 67 - 73

PubMed ID

  • 23636398

Pubmed Central ID

  • PMC3704730

Electronic International Standard Serial Number (EISSN)

  • 1476-4687

Digital Object Identifier (DOI)

  • 10.1038/nature12113


  • eng

Conference Location

  • England