Oncogenic signaling pathways in the Cancer Genome Atlas
Author(s)
Date
2018Source Title
Cell
Print ISSN
0092-8674
Electronic ISSN
1875-9777
Publisher
Cell Press
Volume
173
Issue
2
Pages
321 - 337
Language
English
Type
ArticleItem Usage Stats
349
views
views
1,218
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Abstract
Genetic alterations in signaling pathways that control cell-cycle progression, apoptosis, and cell growth are common hallmarks of cancer, but the extent, mechanisms, and co-occurrence of alterations in these pathways differ between individual tumors and tumor types. Using mutations, copy-number changes, mRNA expression, gene fusions and DNA methylation in 9,125 tumors profiled by The Cancer Genome Atlas (TCGA), we analyzed the mechanisms and patterns of somatic alterations in ten canonical pathways: cell cycle, Hippo, Myc, Notch, Nrf2, PI-3-Kinase/Akt, RTK-RAS, TGFβ signaling, p53 and β-catenin/Wnt. We charted the detailed landscape of pathway alterations in 33 cancer types, stratified into 64 subtypes, and identified patterns of co-occurrence and mutual exclusivity. Eighty-nine percent of tumors had at least one driver alteration in these pathways, and 57% percent of tumors had at least one alteration potentially targetable by currently available drugs. Thirty percent of tumors had multiple targetable alterations, indicating opportunities for combination therapy. An integrated analysis of genetic alterations in 10 signaling pathways in >9,000 tumors profiled by TCGA highlights significant representation of individual and co-occurring actionable alterations in these pathways, suggesting opportunities for targeted and combination therapies.
Keywords
Cancer genome atlasCancer genomics
Combination therapy
Pan-cancer
PanCanAtlas
Precision oncology
Signaling pathways
TCGA
Therapeutics
Whole exome sequencing
Permalink
http://hdl.handle.net/11693/49844Published Version (Please cite this version)
https://doi.org/10.1016/j.cell.2018.03.035Collections
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