Oncogenic signaling pathways in The Cancer Genome Atlas Journal Article


Authors: 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.; and The Cancer Genome Atlas Research Network; Van Allen, E. M.; Cherniack, A. D.; Ciriello, G.; Sander, C.; Schultz, N.
Article Title: 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, 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. 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. © 2018
Keywords: signal transduction; protein kinase b; controlled study; gene mutation; somatic mutation; cell cycle; gene expression; transforming growth factor beta; notch receptor; protein tyrosine kinase; phosphatidylinositol 3 kinase; protein p53; dna methylation; carcinogenesis; cancer genetics; genome analysis; dna; messenger rna; myc protein; gene fusion; ras protein; combination therapy; beta catenin; wnt protein; therapeutics; cancer genomics; signaling pathways; copy number variation; tcga; cancer genome atlas; transcription factor nrf2; pi3k/akt signaling; notch signaling; human; priority journal; article; hippo signaling; whole exome sequencing; precision oncology; pan-cancer; malignant neoplasm; pancanatlas; tgf beta signaling
Journal Title: Cell
Volume: 173
Issue: 2
ISSN: 0092-8674
Publisher: Cell Press  
Date Published: 2018-04-05
Start Page: 321
End Page: 337.e10
Language: English
DOI: 10.1016/j.cell.2018.03.035
PROVIDER: scopus
PUBMED: 29625050
DOI/URL:
Notes: Article -- Export Date: 1 May 2018 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Jianjiong Gao
    62 Gao
  2. Nikolaus D Schultz
    202 Schultz
  3. Benjamin E Gross
    26 Gross
  4. Cyriac Kandoth
    17 Kandoth
  5. Joshua   Armenia
    22 Armenia
  6. Zachary Joseph Heins
    6 Heins
  7. Ritika   Kundra
    16 Kundra
  8. Konnor C La
    7 La
  9. Hongxin Zhang
    7 Zhang
  10. Angelica Ochoa
    4 Ochoa
  11. Walid Khaled Chatila
    11 Chatila