32 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)721-735.e8
JournalCancer Cell
Volume33
Issue number4
DOIs
StatePublished - Apr 9 2018

Fingerprint

Adenocarcinoma
Neoplasms
Genome
Chromosomal Instability
Rectum
Mutation
Gastrointestinal Tract
Colon
Microsatellite Instability
CpG Islands
Aneuploidy
Epigenomics
Colorectal Neoplasms
Stomach
Nucleotides
Phenotype
DNA

Keywords

  • cancer
  • colon
  • colorectal
  • epigenetic
  • esophagus
  • genomic
  • methylation
  • rectum
  • stomach
  • tumor

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

Comparative Molecular Analysis of Gastrointestinal Adenocarcinomas. / The Cancer Genome Atlas Research Network.

In: Cancer Cell, Vol. 33, No. 4, 09.04.2018, p. 721-735.e8.

Research output: Contribution to journalArticle

The Cancer Genome Atlas Research Network 2018, 'Comparative Molecular Analysis of Gastrointestinal Adenocarcinomas', Cancer Cell, vol. 33, no. 4, pp. 721-735.e8. https://doi.org/10.1016/j.ccell.2018.03.010
The Cancer Genome Atlas Research Network. / Comparative Molecular Analysis of Gastrointestinal Adenocarcinomas. In: Cancer Cell. 2018 ; Vol. 33, No. 4. pp. 721-735.e8.
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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.",
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author = "{The Cancer Genome Atlas Research Network} and Yang Liu and Sethi, {Nilay S.} and Toshinori Hinoue and Schneider, {Barbara G.} and Cherniack, {Andrew D.} and Francisco Sanchez-Vega and Seoane, {Jose A.} and Farshad Farshidfar and Reanne Bowlby and Mirazul Islam and Jaegil Kim and Walid Chatila and Rehan Akbani and Kanchi, {Rupa S.} and Rabkin, {Charles S.} and Willis, {Joseph E.} and Wang, {Kenneth Ke Ning} and McCall, {Shannon J.} and Lopa Mishra and Ojesina, {Akinyemi I.} and Susan Bullman and Pedamallu, {Chandra Sekhar} and Lazar, {Alexander J.} and Ryo Sakai and Caesar-Johnson, {Samantha J.} and Demchok, {John A.} and Ina Felau and Melpomeni Kasapi and Ferguson, {Martin L.} and Hutter, {Carolyn M.} and Sofia, {Heidi J.} and Roy Tarnuzzer and Zhining Wang and Liming Yang and Zenklusen, {Jean C.} and Zhang, {Jiashan (Julia)} and Borad, {Mitesh J} and Vishal Chandan and John Cheville and Copland, {John A III} and Flotte, {Thomas J} and Michael Kendrick and Jean-Pierre Kocher and O'Neill, {Brian Patrick} and Patel, {Tushar C} and Petersen, {Gloria M} and Roberts, {Lewis Rowland} and Smallridge, {Robert Christian} and Melissa Stanton and Lizhi Zhang",
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AU - Sanchez-Vega, Francisco

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AU - Bullman, Susan

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AU - Lazar, Alexander J.

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AU - Caesar-Johnson, Samantha J.

AU - Demchok, John A.

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AU - Kasapi, Melpomeni

AU - Ferguson, Martin L.

AU - Hutter, Carolyn M.

AU - Sofia, Heidi J.

AU - Tarnuzzer, Roy

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AU - Yang, Liming

AU - Zenklusen, Jean C.

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AU - Borad, Mitesh J

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AU - Kocher, Jean-Pierre

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AU - Roberts, Lewis Rowland

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KW - cancer

KW - colon

KW - colorectal

KW - epigenetic

KW - esophagus

KW - genomic

KW - methylation

KW - rectum

KW - stomach

KW - tumor

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JF - Cancer Cell

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