Details

Autor(en) / Beteiligte

• Chatila, Walid K.
• Luna, Augustin
• Kantheti, Havish S.
• Daian, Foysal
• Shmulevich, Ilya
• Greene, Casey S.
• Iavarone, Antonio
• Tward, Aaron D.
• Meyerson, Matthew
• Sofia, Heidi J.
• Zenklusen, Jean C.
• Pihl, Todd
• Meier, Sam
• Noble, Michael S.
• Kramer, Roger
• Hegde, Apurva M.
• Li, Jun
• Rao, Arvind
• Abeshouse, Adam
• Schultz, Nikolaus
• Taylor, Barry S.
• Stuart, Joshua M.
• Wong, Christopher K.
• Parker, Joel S.
• Carlsen, Rebecca
• Tam, Angela
• Gabriel, Stacey B.
• Ha, Gavin
• Schumacher, Steven E.
• Maglinte, Dennis T.
• Balu, Saianand
• Skelly, Tara
• Laird, Peter W.
• Lewis, Lora
• Muzny, Donna
• Santibanez, Jireh
• Wang, Min
• Morris, Scott
• Shelton, Candace
• Gerken, Mark
• Costello, Tony
• Reis, Rui M.
• Scapulatempo-Neto, Cristovam
• Singh, Rosy
• Duffy, Elizabeth R.
• Setdikova, Galiya
• Devine, Karen
• Ostrom, Quinn T.
• Deyarmin, Brenda
• Kvecher, Leonid
• Mural, Richard J.
• Latour, Mathieu
• Lacombe, Louis
• Lipp, Eric
• Marks, Jeffrey
• Pickens, Alan
• Shin, Dong M.
• Zhang, Hongzheng
• Calatozzolo, Chiara
• Cuzzubbo, Stefania
• Kycler, Witold
• Giné, Eva
• Beuschlein, Felix
• Borad, Mitesh
• Chandan, Vishal
• Farnell, Michael
• Torbenson, Michael
• Logothetis, Christopher
• Rice, David
• Jakrot, Valerie
• Mann, Graham
• Moncrieff, Marc
• Doruc, Serghei
• Bartlett, John
• Parfitt, Jeremy
• Bifulco, Carlo
• Hayward, Nicholas
• Grazi, Gianluca
• Marino, Mirella
• Naska, Theresa
• Borgia, Jeffrey A.
• Pool, Mark
• Gaudio, Eugenio
• Bell, Sue
• Hilty, Joe
• Sexton, Katherine C.
• Asa, Sylvia L.
• Schlomm, Thorsten
• Prados, Michael
• Smith-McCune, Karen
• Bossler, Aaron
• Moxley, Katherine
• Carlotti, Carlos Gilberto
• Swisher, Elizabeth
• Korst, Robert
• Rathmell, W. Kimryn
• Heath, Sharon
• Aredes, Natália D.
• Mariamidze, Armaz
• Van Allen, Eliezer M.

Titel

Oncogenic Signaling Pathways in The Cancer Genome Atlas

Ist Teil von

• Cell, 2018-04, Vol.173 (2), p.321-337.e10

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2018

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •Alteration map of 10 signaling pathways across 9,125 samples from 33 cancer types•Reusable, curated pathway templates that include a catalogue of driver genes•57% of tumors have at least one potentially actionable alteration in these pathways•Co-occurrence of actionable alterations suggests combination therapy opportunities 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.