Comparative Molecular Analysis of Gastrointestinal Adenocarcinomas

Yang Liu; Nilay S Sethi; Toshinori Hinoue; Barbara G Schneider; Andrew D Cherniack; Francisco Sanchez-Vega; Jose A Seoane; Farshad Farshidfar; Reanne Bowlby; Mirazul Islam; Jaegil Kim; Walid Chatila; Rehan Akbani; Rupa S Kanchi; Charles S Rabkin; Joseph E Willis; Kenneth K Wang; Shannon J McCall; Lopa Mishra; Akinyemi I Ojesina; Susan Bullman; Chandra Sekhar Pedamallu; Alexander J Lazar; Ryo Sakai; Vésteinn Thorsson; Adam J Bass; Peter W Laird

doi:10.1016/j.ccell.2018.03.010

Back

Comparative Molecular Analysis of Gastrointestinal Adenocarcinomas

Journal article

Open access

Peer reviewed

Comparative Molecular Analysis of Gastrointestinal Adenocarcinomas

Yang Liu, Nilay S Sethi, Toshinori Hinoue, Barbara G Schneider, Andrew D Cherniack, Francisco Sanchez-Vega, Jose A Seoane, Farshad Farshidfar, Reanne Bowlby, Mirazul Islam, …

Cancer cell, Vol.33(4), pp.721-735.e8

04/09/2018

DOI: 10.1016/j.ccell.2018.03.010

PMCID: PMC5966039

PMID: 29622466

Files and links (1)

url

https://doi.org/10.1016/j.ccell.2018.03.010View

Published (Version of record) Open Access

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.

Mutation

Adenocarcinoma - classification

Adenocarcinoma - genetics

Aneuploidy

Chromosomal Instability

DNA Methylation

DNA Polymerase II - genetics

DNA-Binding Proteins

Epigenesis, Genetic

Female

Gastrointestinal Neoplasms - classification

Gastrointestinal Neoplasms - genetics

Gene Regulatory Networks

Heterogeneous-Nuclear Ribonucleoproteins - genetics

Humans

Male

Microsatellite Instability

MutL Protein Homolog 1 - genetics

Poly-ADP-Ribose Binding Proteins - genetics

Polymorphism, Single Nucleotide

Proto-Oncogene Proteins p21(ras) - genetics

RNA-Binding Proteins

SOX9 Transcription Factor - genetics

Details

Title: Subtitle: Comparative Molecular Analysis of Gastrointestinal Adenocarcinomas
Creators: Yang Liu - Massachusetts Institute of Technology
Nilay S Sethi - Massachusetts Institute of Technology
Toshinori Hinoue - Van Andel Institute
Barbara G Schneider - Vanderbilt University
Andrew D Cherniack - Massachusetts Institute of Technology
Francisco Sanchez-Vega - Memorial Sloan Kettering Cancer Center
Jose A Seoane - Stanford University
Farshad Farshidfar - University of Calgary
Reanne Bowlby - BC Cancer Agency
Mirazul Islam - Massachusetts Institute of Technology
Jaegil Kim - Massachusetts Institute of Technology
Walid Chatila - Memorial Sloan Kettering Cancer Center
Rehan Akbani - The University of Texas MD Anderson Cancer Center
Rupa S Kanchi - The University of Texas MD Anderson Cancer Center
Charles S Rabkin - National Cancer Institute
Joseph E Willis - Case Western Reserve University
Kenneth K Wang - Mayo Clinic
Shannon J McCall - Duke University
Lopa Mishra - George Washington University
Akinyemi I Ojesina - University of Alabama at Birmingham
Susan Bullman - Harvard University
Chandra Sekhar Pedamallu - Harvard University
Alexander J Lazar - The University of Texas MD Anderson Cancer Center
Ryo Sakai - PharmiWeb Solutions, Bracknell RG12 1QB, UK.
Vésteinn Thorsson - Institute for Systems Biology
Adam J Bass - Massachusetts Institute of Technology
Peter W Laird - Van Andel Institute
Contributors: Cancer Genome Atlas Research Network
Deqin Ma (Contributor) - University of Iowa, Pathology
Mohammed M Milhem (Contributor) - University of Iowa, Internal Medicine
Aaron D Bossler (Contributor) - University of Iowa, Pathology
Resource Type: Journal article
Publication Details: Cancer cell, Vol.33(4), pp.721-735.e8
DOI: 10.1016/j.ccell.2018.03.010
PMID: 29622466
PMCID: PMC5966039
ISSN: 1535-6108
eISSN: 1878-3686
Grant note: U24 CA143843 / NCI NIH HHS I01 BX003732 / BLRD VA R01 CA236591 / NCI NIH HHS U24 CA199461 / NCI NIH HHS U24 CA210957 / NCI NIH HHS U54 HG003079 / NHGRI NIH HHS U24 CA210990 / NCI NIH HHS U24 CA210969 / NCI NIH HHS U24 CA143799 / NCI NIH HHS R01 AA023146 / NIAAA NIH HHS R50 CA221675 / NCI NIH HHS U24 CA143867 / NCI NIH HHS U24 CA143858 / NCI NIH HHS U24 CA143882 / NCI NIH HHS P30 CA008748 / NCI NIH HHS U54 HG003067 / NHGRI NIH HHS U24 CA210999 / NCI NIH HHS U24 CA143835 / NCI NIH HHS U54 HG003273 / NHGRI NIH HHS U24 CA143840 / NCI NIH HHS T32 CA009172 / NCI NIH HHS U24 CA144025 / NCI NIH HHS U24 CA143866 / NCI NIH HHS U24 CA210950 / NCI NIH HHS P01 CA098101 / NCI NIH HHS U24 CA210949 / NCI NIH HHS U24 CA143848 / NCI NIH HHS R01 CA163722 / NCI NIH HHS
Language: English
Date published: 04/09/2018
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Pathology; Internal Medicine
Record Identifier: 9984183992002771

Metrics

11 Record Views

388 Times Cited - Web of Science

See more details