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Oncogenic Signaling Pathways in The Cancer Genome Atlas.


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, TGF? signaling, p53 and ?-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.

SUBMITTER: Sanchez-Vega F 

PROVIDER: S-EPMC6070353 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Oncogenic Signaling Pathways in The Cancer Genome Atlas.

Sanchez-Vega Francisco F   Mina Marco M   Armenia Joshua J   Chatila Walid K WK   Luna Augustin A   La Konnor C KC   Dimitriadoy Sofia S   Liu David L DL   Kantheti Havish S HS   Saghafinia Sadegh S   Chakravarty Debyani D   Daian Foysal F   Gao Qingsong Q   Bailey Matthew H MH   Liang Wen-Wei WW   Foltz Steven M SM   Shmulevich Ilya I   Ding Li L   Heins Zachary Z   Ochoa Angelica A   Gross Benjamin B   Gao Jianjiong J   Zhang Hongxin H   Kundra Ritika R   Kandoth Cyriac C   Bahceci Istemi I   Dervishi Leonard L   Dogrusoz Ugur U   Zhou Wanding W   Shen Hui H   Laird Peter W PW   Way Gregory P GP   Greene Casey S CS   Liang Han H   Xiao Yonghong Y   Wang Chen C   Iavarone Antonio A   Berger Alice H AH   Bivona Trever G TG   Lazar Alexander J AJ   Hammer Gary D GD   Giordano Thomas T   Kwong Lawrence N LN   McArthur Grant G   Huang Chenfei C   Tward Aaron D AD   Frederick Mitchell J MJ   McCormick Frank F   Meyerson Matthew M   Van Allen Eliezer M EM   Cherniack Andrew D AD   Ciriello Giovanni G   Sander Chris C   Schultz Nikolaus N  

Cell 20180401 2


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 pathw  ...[more]

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