Genome doubling shapes the evolution and prognosis of advanced cancers Journal Article


Authors: Bielski, C. M.; Zehir, A.; Penson, A. V.; Donoghue, M. T. A.; Chatila, W.; Armenia, J.; Chang, M. T.; Schram, A. M.; Jonsson, P.; Bandlamudi, C.; Razavi, P.; Iyer, G.; Robson, M. E.; Stadler, Z. K.; Schultz, N.; Baselga, J.; Solit, D. B.; Hyman, D. M.; Berger, M. F.; Taylor, B. S.
Article Title: Genome doubling shapes the evolution and prognosis of advanced cancers
Abstract: Ploidy abnormalities are a hallmark of cancer, but their impact on the evolution and outcomes of cancers is unknown. Here, we identified whole-genome doubling (WGD) in the tumors of nearly 30% of 9,692 prospectively sequenced advanced cancer patients. WGD varied by tumor lineage and molecular subtype, and arose early in carcinogenesis after an antecedent transforming driver mutation. While associated with TP53 mutations, 46% of all WGD arose in TP53-wild-type tumors and in such cases was associated with an E2F-mediated G1 arrest defect, although neither aberration was obligate in WGD tumors. The variability of WGD across cancer types can be explained in part by cancer cell proliferation rates. WGD predicted for increased morbidity across cancer types, including KRAS-mutant colorectal cancers and estrogen receptor-positive breast cancers, independently of established clinical prognostic factors. We conclude that WGD is highly common in cancer and is a macro-evolutionary event associated with poor prognosis across cancer types. © 2018, The Author(s).
Journal Title: Nature Genetics
Volume: 50
Issue: 8
ISSN: 1061-4036
Publisher: Nature Publishing Group  
Date Published: 2018-08-01
Start Page: 1189
End Page: 1195
Language: English
DOI: 10.1038/s41588-018-0165-1
PROVIDER: scopus
PMCID: PMC6072608
PUBMED: 30013179
DOI/URL:
Notes: Article -- Export Date: 4 September 2018 -- Source: Scopus
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MSK Authors
  1. Mark E Robson
    368 Robson
  2. David Solit
    440 Solit
  3. Zsofia Kinga Stadler
    152 Stadler
  4. Gopakumar Vasudeva Iyer
    129 Iyer
  5. David Hyman
    194 Hyman
  6. Ahmet Zehir
    157 Zehir
  7. Michael Forman Berger
    392 Berger
  8. Barry Stephen Taylor
    144 Taylor
  9. Nikolaus D Schultz
    206 Schultz
  10. Alison Michele Schram
    23 Schram
  11. Jose T Baselga
    410 Baselga
  12. Pedram Razavi
    25 Razavi
  13. Matthew   Chang
    21 Chang
  14. Karl Philip Jonsson
    25 Jonsson
  15. Alexander Vincent Penson
    15 Penson
  16. Joshua   Armenia
    24 Armenia
  17. Walid Khaled Chatila
    11 Chatila