Oncogenic Signaling Pathways in The Cancer Genome Atlas

F. Sanchez-Vega, M. Mina, J. Armenia, W. K. Chatila, A. Luna, K. C. La, S. Dimitriadoy, D. L. Liu, H. S. Kantheti, S. Saghafinia, D. Chakravarty, F. Daian, Q. Gao, M. H. Bailey, W. W. Liang, S. M. Foltz, I. Shmulevich, L. Ding, Z. Heins, A. OchoaB. Gross, J. Gao, H. Zhang, R. Kundra, C. Kandoth, I. Bahceci, L. Dervishi, U. Dogrusoz, W. Zhou, H. Shen, P. W. Laird, G. P. Way, C. S. Greene, H. Liang, Y. Xiao, C. Wang, A. Iavarone, A. H. Berger, T. G. Bivona, A. J. Lazar, G. D. Hammer, T. Giordano, L. N. Kwong, G. McArthur, C. Huang, A. D. Tward, M. J. Frederick, F. McCormick, M. Meyerson, Cancer Genome Atlas Research Network, E. M. Van Allen, A. D. Cherniack, G. Ciriello, C. Sander, N. Schultz, M. (come contributors) Marino

Research output: Contribution to journalArticle

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, TGFbeta signaling, p53 and beta-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.
Original languageEnglish
Pages (from-to)321-337.e10
JournalCell
Volume173
Issue number2
DOIs
Publication statusPublished - Apr 5 2018
Externally publishedYes

Keywords

  • PanCanAtlas
  • TCGA
  • cancer genome atlas
  • cancer genomics
  • combination therapy
  • pan-cancer
  • precision oncology
  • signaling pathways
  • therapeutics
  • whole exome sequencing

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  • Cite this

    Sanchez-Vega, F., Mina, M., Armenia, J., Chatila, W. K., Luna, A., La, K. C., Dimitriadoy, S., Liu, D. L., Kantheti, H. S., Saghafinia, S., Chakravarty, D., Daian, F., Gao, Q., Bailey, M. H., Liang, W. W., Foltz, S. M., Shmulevich, I., Ding, L., Heins, Z., ... Marino, M. . C. (2018). Oncogenic Signaling Pathways in The Cancer Genome Atlas. Cell, 173(2), 321-337.e10. https://doi.org/S0092-8674(18)30359-3 [pii]