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Comparative molecular analysis of gastrointestinal adenocarcinomas

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Title: Comparative molecular analysis of gastrointestinal adenocarcinomas
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
Thorsson, V
Bass, AJ
Laird, PW
Item Type: Journal Article
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.
Issue Date: 9-Apr-2018
Date of Acceptance: 7-Mar-2018
URI: http://hdl.handle.net/10044/1/71216
DOI: https://doi.org/10.1016/j.ccell.2018.03.010
ISSN: 1535-6108
Publisher: Elsevier
Start Page: 721
End Page: 735.e8
Journal / Book Title: Cancer Cell
Volume: 33
Issue: 4
Copyright Statement: © 2018 Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Sponsor/Funder: SAIC-F-Frederick, Inc
Leidos Biomedical Research, Inc.
Funder's Grant Number: TCGA Pilot Program
15Y011ST
Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
Cell Biology
GENERATION SEQUENCING DATA
COLORECTAL-CANCER
MICROSATELLITE INSTABILITY
GASTRIC-CANCER
HUMAN-CELLS
STEM-CELLS
NK CELLS
DNA
MUTATIONS
GENOME
cancer
colon
colorectal
epigenetic
esophagus
genomic
methylation
rectum
stomach
tumor
Adenocarcinoma
Aneuploidy
Chromosomal Instability
DNA Methylation
DNA Polymerase II
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)
SOX9 Transcription Factor
Cancer Genome Atlas Research Network
Humans
Adenocarcinoma
Gastrointestinal Neoplasms
Aneuploidy
Chromosomal Instability
DNA Polymerase II
Heterogeneous-Nuclear Ribonucleoproteins
DNA Methylation
Epigenesis, Genetic
Mutation
Polymorphism, Single Nucleotide
Female
Male
Proto-Oncogene Proteins p21(ras)
Microsatellite Instability
Gene Regulatory Networks
SOX9 Transcription Factor
MutL Protein Homolog 1
Poly-ADP-Ribose Binding Proteins
Science & Technology
Life Sciences & Biomedicine
Oncology
Cell Biology
GENERATION SEQUENCING DATA
COLORECTAL-CANCER
MICROSATELLITE INSTABILITY
GASTRIC-CANCER
HUMAN-CELLS
STEM-CELLS
NK CELLS
DNA
MUTATIONS
GENOME
Oncology & Carcinogenesis
1112 Oncology and Carcinogenesis
1109 Neurosciences
Publication Status: Published
Open Access location: https://www.cell.com/cancer-cell/fulltext/S1535-6108(18)30114-4
Online Publication Date: 2018-04-02
Appears in Collections:Department of Surgery and Cancer