Year: 2019
Type: article
Study design: Observational Study
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 TP53mutations, but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1Aand 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.
DOI: 10.17615/70ej-xj89
Author: Perou, Charles
Language: English
Subfield: Obstetrics and Gynecology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: The Human Genome Sequencing Center, Harvard Genome Characterization Center, Cancer transcriptome characterization using massively parallel DNA sequencing, G9000009266, G9000022338, G9000036768, G9000037270, G9000111900, G9000130770, G9000134348, G9000197591, G9000244592, G9000339650, G9000343359, G9000351369
OpenAlex ID: W4300719696