Integrated genomic characterization of endometrial carcinoma.
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ABSTRACT:
SUBMITTER: Cancer Genome Atlas Research Network
PROVIDER: S-EPMC3704730 | biostudies-literature | 2013 May
REPOSITORIES: biostudies-literature
Publications
Integrated genomic characterization of endometrial carcinoma.
Kandoth Cyriac C Schultz Nikolaus N Cherniack Andrew D AD Akbani Rehan R Liu Yuexin Y Shen Hui H Robertson A Gordon AG Pashtan Itai I Shen Ronglai R Benz Christopher C CC Yau Christina C Laird Peter W PW Ding Li L Zhang Wei W Mills Gordon B GB Kucherlapati Raju R Mardis Elaine R ER Levine Douglas A DA
Nature 20130501 7447
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 ...[more]
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Project description:We undertook a comprehensive proteogenomic characterization of 95 prospectively collected endometrial carcinomas, comprising 83 endometrioid and 12 serous tumors. This analysis revealed possible new consequences of perturbations to the p53 and Wnt/β-catenin pathways, identified a potential role for circRNAs in the epithelial-mesenchymal transition, and provided new information about proteomic markers of clinical and genomic tumor subgroups, including relationships to known druggable pathways. An extensive genome-wide acetylation survey yielded insights into regulatory mechanisms linking Wnt signaling and histone acetylation. We also characterized aspects of the tumor immune landscape, including immunogenic alterations, neoantigens, common cancer/testis antigens, and the immune microenvironment, all of which can inform immunotherapy decisions. Collectively, our multi-omic analyses provide a valuable resource for researchers and clinicians, identify new molecular associations of potential mechanistic significance in the development of endometrial cancers, and suggest novel approaches for identifying potential therapeutic targets.
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