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.
journal_name
Celljournal_title
Cellauthors
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 WW,Foltz SM,Shmulevich I,Ding L,Heins Z,Ochoa A,Gross B,Gao J,Zdoi
10.1016/j.cell.2018.03.035subject
Has Abstractpub_date
2018-04-05 00:00:00pages
321-337.e10issue
2eissn
0092-8674issn
1097-4172pii
S0092-8674(18)30359-3journal_volume
173pub_type
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