TY - JOUR
T1 - Oncogenic Signaling Pathways in The Cancer Genome Atlas
AU - The Cancer Genome Atlas Research Network
AU - Sanchez-Vega, Francisco
AU - Mina, Marco
AU - Armenia, Joshua
AU - Chatila, Walid K.
AU - Luna, Augustin
AU - La, Konnor C.
AU - Dimitriadoy, Sofia
AU - Liu, David L.
AU - Kantheti, Havish S.
AU - Saghafinia, Sadegh
AU - Chakravarty, Debyani
AU - Daian, Foysal
AU - Gao, Qingsong
AU - Bailey, Matthew H.
AU - Liang, Wen Wei
AU - Foltz, Steven M.
AU - Shmulevich, Ilya
AU - Ding, Li
AU - Heins, Zachary
AU - Ochoa, Angelica
AU - Gross, Benjamin
AU - Gao, Jianjiong
AU - Zhang, Hongxin
AU - Kundra, Ritika
AU - Kandoth, Cyriac
AU - Bahceci, Istemi
AU - Dervishi, Leonard
AU - Dogrusoz, Ugur
AU - Zhou, Wanding
AU - Shen, Hui
AU - Laird, Peter W.
AU - Way, Gregory P.
AU - Greene, Casey S.
AU - Liang, Han
AU - Xiao, Yonghong
AU - Wang, Chen
AU - Iavarone, Antonio
AU - Berger, Alice H.
AU - Bivona, Trever G.
AU - Lazar, Alexander J.
AU - Hammer, Gary D.
AU - Giordano, Thomas
AU - Kwong, Lawrence N.
AU - McArthur, Grant
AU - Huang, Chenfei
AU - Tward, Aaron D.
AU - Frederick, Mitchell J.
AU - McCormick, Frank
AU - Meyerson, Matthew
AU - Baudin, Eric
N1 - Publisher Copyright:
© 2018
PY - 2018/4/5
Y1 - 2018/4/5
N2 - 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.
AB - 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.
KW - PanCanAtlas
KW - TCGA
KW - cancer genome atlas
KW - cancer genomics
KW - combination therapy
KW - pan-cancer
KW - precision oncology
KW - signaling pathways
KW - therapeutics
KW - whole exome sequencing
UR - http://www.scopus.com/inward/record.url?scp=85044966521&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2018.03.035
DO - 10.1016/j.cell.2018.03.035
M3 - Article
C2 - 29625050
AN - SCOPUS:85044966521
SN - 0092-8674
VL - 173
SP - 321-337.e10
JO - Cell
JF - Cell
IS - 2
ER -