Genomic and Functional Approaches to Understanding Cancer Aneuploidy

Alison M Taylor; Juliann Shih; Gavin Ha; Galen F Gao; Xiaoyang Zhang; Ashton C Berger; Steven E Schumacher; Chen Wang; Hai Hu; Jianfang Liu; Alexander J Lazar; Andrew D Cherniack; Rameen Beroukhim; Matthew Meyerson

doi:10.1016/j.ccell.2018.03.007

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Genomic and Functional Approaches to Understanding Cancer Aneuploidy

Journal article

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Peer reviewed

Genomic and Functional Approaches to Understanding Cancer Aneuploidy

Alison M Taylor, Juliann Shih, Gavin Ha, Galen F Gao, Xiaoyang Zhang, Ashton C Berger, Steven E Schumacher, Chen Wang, Hai Hu, Jianfang Liu, …

Cancer cell, Vol.33(4), pp.676-689.e3

04/09/2018

DOI: 10.1016/j.ccell.2018.03.007

PMCID: PMC6028190

PMID: 29622463

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Abstract

Aneuploidy, whole chromosome or chromosome arm imbalance, is a near-universal characteristic of human cancers. In 10,522 cancer genomes from The Cancer Genome Atlas, aneuploidy was correlated with TP53 mutation, somatic mutation rate, and expression of proliferation genes. Aneuploidy was anti-correlated with expression of immune signaling genes, due to decreased leukocyte infiltrates in high-aneuploidy samples. Chromosome arm-level alterations show cancer-specific patterns, including loss of chromosome arm 3p in squamous cancers. We applied genome engineering to delete 3p in lung cells, causing decreased proliferation rescued in part by chromosome 3 duplication. This study defines genomic and phenotypic correlates of cancer aneuploidy and provides an experimental approach to study chromosome arm aneuploidy.

Cell Cycle

Aneuploidy

Carcinoma, Squamous Cell - genetics

Cell Proliferation

Chromosome Aberrations

Chromosome Deletion

Chromosomes, Human, Pair 3 - genetics

Databases, Genetic

Genomics - methods

Humans

Mutation Rate

Tumor Suppressor Protein p53 - genetics

Details

Title: Subtitle: Genomic and Functional Approaches to Understanding Cancer Aneuploidy
Creators: Alison M Taylor - Broad Institute
Juliann Shih - Broad Institute
Gavin Ha - Broad Institute
Galen F Gao - Broad Institute
Xiaoyang Zhang - Broad Institute
Ashton C Berger - Broad Institute
Steven E Schumacher - Broad Institute
Chen Wang - Mayo Clinic
Hai Hu
Jianfang Liu
Alexander J Lazar - The University of Texas MD Anderson Cancer Center
Andrew D Cherniack - Harvard University
Rameen Beroukhim - Harvard University
Matthew Meyerson - Harvard University
Contributors: Cancer Genome Atlas Research Network (Contributor)
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.676-689.e3
DOI: 10.1016/j.ccell.2018.03.007
PMID: 29622463
PMCID: PMC6028190
NLM abbreviation: Cancer Cell
ISSN: 1535-6108
eISSN: 1878-3686
Grant note: U24 CA210950 / NCI NIH HHS U24 CA210990 / NCI NIH HHS U24 CA210949 / NCI NIH HHS R01 CA163722 / NCI NIH HHS U24 CA210957 / NCI NIH HHS R35 CA197568 / NCI NIH HHS R01 CA188228 / NCI NIH HHS
Language: English
Date published: 04/09/2018
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Pathology; Internal Medicine
Record Identifier: 9984185168702771

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