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Comparative Molecular Analysis of Gastrointestinal Adenocarcinomas. Cancer Cell 2018 Apr 09;33(4):721-735.e8

Date

04/07/2018

Pubmed ID

29622466

Pubmed Central ID

PMC5966039

DOI

10.1016/j.ccell.2018.03.010

Scopus ID

2-s2.0-85044904369   268 Citations

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.

Author List

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

Author

Akinyemi Ojesina MD, PhD Assistant Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

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