Comparative Molecular Analysis of Gastrointestinal Adenocarcinomas.

Published

Journal Article

We analyzed 921 adenocarcinomas of the esophagus, stomach, colon, and rectum to examine shared and distinguishing molecular characteristics of gastrointestinal tract adenocarcinomas (GIACs). Hypermutated tumors were distinct regardless of cancer type and comprised those enriched for insertions/deletions, representing microsatellite instability cases with epigenetic silencing of MLH1 in the context of CpG island methylator phenotype, plus tumors with elevated single-nucleotide variants associated with mutations in POLE. Tumors with chromosomal instability were diverse, with gastroesophageal adenocarcinomas harboring fragmented genomes associated with genomic doubling and distinct mutational signatures. We identified a group of tumors in the colon and rectum lacking hypermutation and aneuploidy termed genome stable and enriched in DNA hypermethylation and mutations in KRAS, SOX9, and PCBP1.

Full Text

Duke Authors

Cited Authors

  • Liu, Y; Sethi, NS; Hinoue, T; Schneider, BG; Cherniack, AD; Sanchez-Vega, F; Seoane, JA; Farshidfar, F; Bowlby, R; Islam, M; Kim, J; Chatila, W; Akbani, R; Kanchi, RS; Rabkin, CS; Willis, JE; Wang, KK; McCall, SJ; Mishra, L; Ojesina, AI; Bullman, S; Pedamallu, CS; Lazar, AJ; Sakai, R; Cancer Genome Atlas Research Network, ; Thorsson, V; Bass, AJ; Laird, PW

Published Date

  • April 2, 2018

Published In

Volume / Issue

  • 33 / 4

Start / End Page

  • 721 - 735.e8

PubMed ID

  • 29622466

Pubmed Central ID

  • 29622466

Electronic International Standard Serial Number (EISSN)

  • 1878-3686

International Standard Serial Number (ISSN)

  • 1535-6108

Digital Object Identifier (DOI)

  • 10.1016/j.ccell.2018.03.010

Language

  • eng