Comparative molecular analysis of gastrointestinal adenocarcinomas Journal Article


Authors: Liu, Y.; Sethi, N. S.; Hinoue, T.; Schneider, B. G.; Cherniack, A. D.; Sanchez-Vega, F.; Seoane, J. A.; Farshidfar, F.; Bowlby, R.; Islam, M.; Kim, J.; Chatila, W.; Akbani, R.; Kanchi, R. S.; Rabkin, C. S.; Willis, J. E.; Wang, K. K.; McCall, S. J.; Mishra, L.; Ojesina, A. I.; Bullman, S.; Pedamallu, C. S.; Lazar, A. J.; Sakai, R.; The Cancer Genome Atlas Research Network; Thorsson, V.; Bass, A. J.; Laird, P. W.
Article Title: Comparative molecular analysis of gastrointestinal adenocarcinomas
Abstract: 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. Liu et al. analyze 921 gastrointestinal (GI) tract adenocarcinomas and find that hypermutated tumors are enriched for insertions/deletions, upper GI tumors with chromosomal instability harbor fragmented genomes, and a group of genome-stable colorectal tumors are enriched in mutations in SOX9 and PCBP1. © 2018 Elsevier Inc.
Keywords: methylation; tumor; colon; esophagus; stomach; rectum; colorectal; epigenetic; genomic; cancer
Journal Title: Cancer Cell
Volume: 33
Issue: 4
ISSN: 1535-6108
Publisher: Cell Press  
Date Published: 2018-04-09
Start Page: 721
End Page: 735.e8
Language: English
DOI: 10.1016/j.ccell.2018.03.010
PROVIDER: scopus
PUBMED: 29622466
PMCID: PMC5966039
DOI/URL:
Notes: Article -- Export Date: 1 May 2018 -- Source: Scopus
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  1. Walid Khaled Chatila
    102 Chatila