Comparative Molecular Analysis of Gastrointestinal Adenocarcinomas.

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
Cancer Cell. 2018 33 (4): 721-735.e8

PMID: 29622466 · PMCID: PMC5966039 · DOI:10.1016/j.ccell.2018.03.010

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.

Copyright © 2018 Elsevier Inc. All rights reserved.

MeSH Terms (19)

Adenocarcinoma Aneuploidy Chromosomal Instability DNA Methylation DNA Polymerase II Epigenesis, Genetic Female Gastrointestinal Neoplasms Gene Regulatory Networks Heterogeneous-Nuclear Ribonucleoproteins Humans Male Microsatellite Instability Mutation MutL Protein Homolog 1 Poly-ADP-Ribose Binding Proteins Polymorphism, Single Nucleotide Proto-Oncogene Proteins p21(ras) SOX9 Transcription Factor

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