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Oncogenic signaling pathways in the cancer genome atlas

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Title: Oncogenic signaling pathways in the cancer genome atlas
Authors: Sanchez-Vega, F
Mina, M
Armenia, J
Chatila, WK
Luna, A
La, KC
Dimitriadoy, S
Liu, DL
Kantheti, HS
Saghafinia, S
Chakravarty, D
Daian, F
Gao, Q
Bailey, MH
Liang, W-W
Foltz, SM
Shmulevich, I
Ding, L
Heins, Z
Ochoa, A
Gross, B
Gao, J
Zhang, H
Kundra, R
Kandoth, C
Bahceci, I
Dervishi, L
Dogrusoz, U
Zhou, W
Shen, H
Laird, PW
Way, GP
Greene, CS
Liang, H
Xiao, Y
Wang, C
Iavarone, A
Berger, AH
Bivona, TG
Lazar, AJ
Hammer, GD
Giordano, T
Kwong, LN
McArthur, G
Huang, C
Tward, AD
Frederick, MJ
McCormick, F
Meyerson, M
Van Allen, EM
Cherniack, AD
Ciriello, G
Sander, C
Schultz, N
Item Type: Journal Article
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.
Issue Date: 5-Apr-2018
Date of Acceptance: 15-Mar-2018
URI: http://hdl.handle.net/10044/1/71221
DOI: https://doi.org/10.1016/j.cell.2018.03.035
ISSN: 0092-8674
Publisher: Elsevier
Start Page: 321
End Page: 337.e10
Journal / Book Title: Cell
Volume: 173
Issue: 2
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
Biochemistry & Molecular Biology
Cell Biology
COMPREHENSIVE MOLECULAR CHARACTERIZATION
LANDSCAPE
GENES
EXPRESSION
SIGNATURES
MUTATIONS
PanCanAtlas
TCGA
cancer genome atlas
cancer genomics
combination therapy
pan-cancer
precision oncology
signaling pathways
therapeutics
whole exome sequencing
Databases, Genetic
Genes, Neoplasm
Humans
Neoplasms
Phosphatidylinositol 3-Kinases
Signal Transduction
Transforming Growth Factor beta
Tumor Suppressor Protein p53
Wnt Proteins
Cancer Genome Atlas Research Network
Humans
Neoplasms
Transforming Growth Factor beta
Signal Transduction
Databases, Genetic
Tumor Suppressor Protein p53
Wnt Proteins
Genes, Neoplasm
Phosphatidylinositol 3-Kinases
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Cell Biology
COMPREHENSIVE MOLECULAR CHARACTERIZATION
LANDSCAPE
GENES
EXPRESSION
SIGNATURES
MUTATIONS
06 Biological Sciences
11 Medical and Health Sciences
Developmental Biology
Publication Status: Published
Open Access location: https://www.cell.com/cell/fulltext/S0092-8674(18)30359-3?_returnURL=https:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867418303593%3Fshowall%3Dtrue
Online Publication Date: 2018-04-05
Appears in Collections:Department of Surgery and Cancer