Integrated genomic characterization of endometrial carcinoma
Name
Lander_Integrated genomic characterization.pdf
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2.28 MB
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Author(s) •
Park, Peter J.
Lander, Eric Steven
Date Issued
May 2013
Journal
Nature
Publisher
Nature Publishing Group
Citation
Getz, Gad, Stacey B. Gabriel, Kristian Cibulskis, Eric Lander, Andrey Sivachenko, Carrie Sougnez, Mike Lawrence, et al. “Integrated genomic characterization of endometrial carcinoma.” Nature 497, no. 7447 (May 1, 2013): 67-73.
Version
Author's final manuscript
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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DOI of Published Version
https://doi.org/10.1038/nature12113