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Cell-of-Origin patterns dominate the molecular classification of 10,000 tumors from 33 types of cancer

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Title: Cell-of-Origin patterns dominate the molecular classification of 10,000 tumors from 33 types of cancer
Authors: Hoadley, KA
Yau, C
Hinoue, T
Wolf, DM
Lazar, AJ
Drill, E
Shen, R
Taylor, AM
Cherniack, AD
Thorsson, V
Akbani, R
Bowlby, R
Wong, CK
Wiznerowicz, M
Sanchez-Vega, F
Robertson, AG
Schneider, BG
Lawrence, MS
Noushmehr, H
Malta, TM
Stuart, JM
Benz, CC
Laird, PW
Item Type: Journal Article
Abstract: We conducted comprehensive integrative molecular analyses of the complete set of tumors in The Cancer Genome Atlas (TCGA), consisting of approximately 10,000 specimens and representing 33 types of cancer. We performed molecular clustering using data on chromosome-arm-level aneuploidy, DNA hypermethylation, mRNA, and miRNA expression levels and reverse-phase protein arrays, of which all, except for aneuploidy, revealed clustering primarily organized by histology, tissue type, or anatomic origin. The influence of cell type was evident in DNA-methylation-based clustering, even after excluding sites with known preexisting tissue-type-specific methylation. Integrative clustering further emphasized the dominant role of cell-of-origin patterns. Molecular similarities among histologically or anatomically related cancer types provide a basis for focused pan-cancer analyses, such as pan-gastrointestinal, pan-gynecological, pan-kidney, and pan-squamous cancers, and those related by stemness features, which in turn may inform strategies for future therapeutic development.
Issue Date: 5-Apr-2018
Date of Acceptance: 8-Mar-2018
URI: http://hdl.handle.net/10044/1/71223
DOI: https://doi.org/10.1016/j.cell.2018.03.022
ISSN: 0092-8674
Publisher: Elsevier
Start Page: 291
End Page: 304.e6
Journal / Book Title: Cell
Volume: 173
Issue: 2
Copyright Statement: © 2018 The Authors. 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
Biochemistry & Molecular Biology
Cell Biology
INTEGRATED GENOMIC CHARACTERIZATION
UNKNOWN PRIMARY
BREAST
SIMILARITIES
SIGNATURE
DISCOVERY
ACCURATE
TCGA
cancer
cell-of-origin
genome
methylome
organs
proteome
subtypes
tissues
transcriptome
Aneuploidy
Chromosomes
Cluster Analysis
CpG Islands
DNA Methylation
Databases, Factual
Humans
MicroRNAs
Mutation
Neoplasm Proteins
Neoplasms
RNA, Messenger
Cancer Genome Atlas Network
Chromosomes
Humans
Neoplasms
Aneuploidy
Neoplasm Proteins
MicroRNAs
RNA, Messenger
Cluster Analysis
DNA Methylation
CpG Islands
Mutation
Databases, Factual
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Cell Biology
INTEGRATED GENOMIC CHARACTERIZATION
UNKNOWN PRIMARY
BREAST
SIMILARITIES
SIGNATURE
DISCOVERY
ACCURATE
06 Biological Sciences
11 Medical and Health Sciences
Developmental Biology
Publication Status: Published
Online Publication Date: 2018-04-05
Appears in Collections:Department of Surgery and Cancer