title: Integrated genomic characterization of endometrial carcinoma.
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.
authors: Cyriac
authors: C
authors: Kandoth
authors: Nikolaus
authors: N
authors: Schultz
authors: Andrew D
authors: AD
authors: Cherniack
authors: Rehan
authors: R
authors: Akbani
authors: Yuexin
authors: Y
authors: Liu
authors: Hui
authors: H
authors: Shen
authors: A Gordon
authors: AG
authors: Robertson
authors: Itai
authors: I
authors: Pashtan
authors: Ronglai
authors: R
authors: Shen
authors: Christopher C
authors: CC
authors: Benz
authors: Christina
authors: C
authors: Yau
authors: Peter W
authors: PW
authors: Laird
authors: Li
authors: L
authors: Ding
authors: Wei
authors: W
authors: Zhang
authors: Gordon B
authors: GB
authors: Mills
authors: Raju
authors: R
authors: Kucherlapati
authors: Elaine R
authors: ER
authors: Mardis
authors: Douglas A
authors: DA
authors: Levine
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics; D002869:Chromosome Aberrations; D056915:DNA Copy Number Variations / Q000235:genetics; D004252:DNA Mutational Analysis; D004257:DNA Polymerase II / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D016889:Endometrial Neoplasms / Q000145:classification* / Q000235:genetics*; D059472:Exome / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human / Q000235:genetics*; D023281:Genomics; D006801:Humans; D010051:Ovarian Neoplasms / Q000235:genetics; D000075223:Poly-ADP-Ribose Binding Proteins; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics
chemical_list: C503805:ARID5B protein, human; D004268:DNA-Binding Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D014157:Transcription Factors; D004257:DNA Polymerase II; C119525:POLE protein, human
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