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. Ochoa & 36 others B. 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

Fingerprint

Atlases
Tumors
Genes
Genome
Neoplasms
Cells
beta Catenin
Cell growth
Phosphatidylinositol 3-Kinases
Gene expression
Transforming Growth Factor beta
Fusion reactions
Gene Fusion
DNA Methylation
Apoptosis
Cell Cycle Checkpoints
Messenger RNA
Cell Cycle
Pharmaceutical Preparations
Mutation

Keywords

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

Cite this

Sanchez-Vega, F., Mina, M., Armenia, J., Chatila, W. K., Luna, A., La, K. C., ... 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]

Oncogenic Signaling Pathways in The Cancer Genome Atlas. / 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.; Ochoa, A.; Gross, B.; Gao, J.; Zhang, H.; Kundra, R.; Kandoth, C.; Bahceci, I.; Dervishi, L.; Dogrusoz, U.; Zhou, W.; Shen, H.; Laird, P. W.; Way, G. P.; Greene, C. S.; Liang, H.; Xiao, Y.; Wang, C.; Iavarone, A.; Berger, A. H.; Bivona, T. G.; Lazar, A. J.; Hammer, G. D.; Giordano, T.; Kwong, L. N.; McArthur, G.; Huang, C.; Tward, A. D.; Frederick, M. J.; McCormick, F.; Meyerson, M.; Network, Cancer Genome Atlas Research; Allen, E. M. Van; Cherniack, A. D.; Ciriello, G.; Sander, C.; Schultz, N.; Marino, M. (come contributors).

In: Cell, Vol. 173, No. 2, 05.04.2018, p. 321-337.e10.

Research output: Contribution to journalArticle

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, Zhang, H, Kundra, R, Kandoth, C, Bahceci, I, Dervishi, L, Dogrusoz, U, Zhou, W, Shen, H, Laird, PW, Way, GP, Greene, CS, Liang, H, Xiao, Y, Wang, C, Iavarone, A, Berger, AH, Bivona, TG, Lazar, AJ, Hammer, GD, Giordano, T, Kwong, LN, McArthur, G, Huang, C, Tward, AD, Frederick, MJ, McCormick, F, Meyerson, M, Network, CGAR, Allen, EMV, Cherniack, AD, Ciriello, G, Sander, C, Schultz, N & Marino, MC 2018, 'Oncogenic Signaling Pathways in The Cancer Genome Atlas', Cell, vol. 173, no. 2, pp. 321-337.e10. https://doi.org/S0092-8674(18)30359-3 [pii]
Sanchez-Vega F, Mina M, Armenia J, Chatila WK, Luna A, La KC et al. Oncogenic Signaling Pathways in The Cancer Genome Atlas. Cell. 2018 Apr 5;173(2):321-337.e10. https://doi.org/S0092-8674(18)30359-3 [pii]
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. ; Ochoa, A. ; Gross, B. ; Gao, J. ; Zhang, H. ; Kundra, R. ; Kandoth, C. ; Bahceci, I. ; Dervishi, L. ; Dogrusoz, U. ; Zhou, W. ; Shen, H. ; Laird, P. W. ; Way, G. P. ; Greene, C. S. ; Liang, H. ; Xiao, Y. ; Wang, C. ; Iavarone, A. ; Berger, A. H. ; Bivona, T. G. ; Lazar, A. J. ; Hammer, G. D. ; Giordano, T. ; Kwong, L. N. ; McArthur, G. ; Huang, C. ; Tward, A. D. ; Frederick, M. J. ; McCormick, F. ; Meyerson, M. ; Network, Cancer Genome Atlas Research ; Allen, E. M. Van ; Cherniack, A. D. ; Ciriello, G. ; Sander, C. ; Schultz, N. ; Marino, M. (come contributors). / Oncogenic Signaling Pathways in The Cancer Genome Atlas. In: Cell. 2018 ; Vol. 173, No. 2. pp. 321-337.e10.
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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.",
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TY - JOUR

T1 - Oncogenic Signaling Pathways in The Cancer Genome Atlas

AU - Sanchez-Vega, F.

AU - Mina, M.

AU - Armenia, J.

AU - Chatila, W. K.

AU - Luna, A.

AU - La, K. C.

AU - Dimitriadoy, S.

AU - Liu, D. L.

AU - Kantheti, H. S.

AU - Saghafinia, S.

AU - Chakravarty, D.

AU - Daian, F.

AU - Gao, Q.

AU - Bailey, M. H.

AU - Liang, W. W.

AU - Foltz, S. M.

AU - Shmulevich, I.

AU - Ding, L.

AU - Heins, Z.

AU - Ochoa, A.

AU - Gross, B.

AU - Gao, J.

AU - Zhang, H.

AU - Kundra, R.

AU - Kandoth, C.

AU - Bahceci, I.

AU - Dervishi, L.

AU - Dogrusoz, U.

AU - Zhou, W.

AU - Shen, H.

AU - Laird, P. W.

AU - Way, G. P.

AU - Greene, C. S.

AU - Liang, H.

AU - Xiao, Y.

AU - Wang, C.

AU - Iavarone, A.

AU - Berger, A. H.

AU - Bivona, T. G.

AU - Lazar, A. J.

AU - Hammer, G. D.

AU - Giordano, T.

AU - Kwong, L. N.

AU - McArthur, G.

AU - Huang, C.

AU - Tward, A. D.

AU - Frederick, M. J.

AU - McCormick, F.

AU - Meyerson, M.

AU - Network, Cancer Genome Atlas Research

AU - Allen, E. M. Van

AU - Cherniack, A. D.

AU - Ciriello, G.

AU - Sander, C.

AU - Schultz, N.

AU - Marino, M. (come contributors)

N1 - LR: 20180802; CI: Copyright (c) 2018; GR: U24 CA143882/CA/NCI NIH HHS/United States; GR: U54 HG003067/HG/NHGRI NIH HHS/United States; GR: U24 CA143835/CA/NCI NIH HHS/United States; GR: U24 CA143866/CA/NCI NIH HHS/United States; GR: U24 CA210950/CA/NCI NIH HHS/United States; GR: U24 CA143845/CA/NCI NIH HHS/United States; GR: U24 CA143799/CA/NCI NIH HHS/United States; GR: U54 HG003273/HG/NHGRI NIH HHS/United States; GR: U24 CA144025/CA/NCI NIH HHS/United States; GR: U24 CA143840/CA/NCI NIH HHS/United States; GR: U24 CA143843/CA/NCI NIH HHS/United States; GR: U24 CA143858/CA/NCI NIH HHS/United States; GR: U24 CA143848/CA/NCI NIH HHS/United States; GR: U24 CA210957/CA/NCI NIH HHS/United States; GR: U54 HG003079/HG/NHGRI NIH HHS/United States; GR: U24 CA210949/CA/NCI NIH HHS/United States; GR: U24 CA143883/CA/NCI NIH HHS/United States; GR: U24 CA143867/CA/NCI NIH HHS/United States; JID: 0413066; NIHMS957693; OTO: NOTNLM; PMCR: 2019/04/05 00:00; 2017/11/17 00:00 [received]; 2018/02/28 00:00 [revised]; 2018/03/15 00:00 [accepted]; 2019/04/05 00:00 [pmc-release]; 2018/04/07 06:00 [entrez]; 2018/04/07 06:00 [pubmed]; 2018/04/07 06:00 [medline]; ppublish

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, 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.

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, 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.

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

U2 - S0092-8674(18)30359-3 [pii]

DO - S0092-8674(18)30359-3 [pii]

M3 - Article

VL - 173

SP - 321-337.e10

JO - Cell

JF - Cell

SN - 0092-8674

IS - 2

ER -