The mutational landscape of adenoid cystic carcinoma Journal Article


Authors: Ho, A. S.; Kannan, K.; Roy, D. M.; Morris, L. G. T.; Ganly, I.; Katabi, N.; Ramaswami, D.; Walsh, L. A.; Eng, S.; Huse, J. T.; Zhang, J.; Dolgalev, I.; Huberman, K.; Heguy, A.; Viale, A.; Drobnjak, M.; Leversha, M. A.; Rice, C. E.; Singh, B.; Iyer, N. G.; Leemans, C. R.; Bloemena, E.; Ferris, R. L.; Seethala, R. R.; Gross, B. E.; Liang, Y.; Sinha, R.; Peng, L.; Raphael, B. J.; Turcan, S.; Gong, Y.; Schultz, N.; Kim, S.; Chiosea, S.; Shah, J. P.; Sander, C.; Lee, W.; Chan, T. A.
Article Title: The mutational landscape of adenoid cystic carcinoma
Abstract: Adenoid cystic carcinomas (ACCs) are among the most enigmatic of human malignancies. These aggressive salivary gland cancers frequently recur and metastasize despite definitive treatment, with no known effective chemotherapy regimen. Here we determined the ACC mutational landscape and report the exome or whole-genome sequences of 60 ACC tumor-normal pairs. These analyses identified a low exonic somatic mutation rate (0.31 non-silent events per megabase) and wide mutational diversity. Notably, we found mutations in genes encoding chromatin-state regulators, such as SMARCA2, CREBBP and KDM6A, suggesting that there is aberrant epigenetic regulation in ACC oncogenesis. Mutations in genes central to the DNA damage response and protein kinase A signaling also implicate these processes. We observed MYB-NFIB translocations and somatic mutations in MYB-associated genes, solidifying the role of these aberrations as critical events in ACC. Lastly, we identified recurrent mutations in the FGF-IGF-PI3K pathway (30% of tumors) that might represent new avenues for therapy. Collectively, our observations establish a molecular foundation for understanding and exploring new treatments for ACC. © 2013 Nature America, Inc. All rights reserved.
Keywords: signal transduction; somatomedin; unclassified drug; gene mutation; gene sequence; major clinical study; somatic mutation; missense mutation; mutation; case-control studies; genetic analysis; animals; dna damage; cells, cultured; gene expression profiling; models, biological; ubiquitin protein ligase; protein; cercopithecus aethiops; cos cells; phosphatidylinositol 3 kinase; protein p53; cell transformation, neoplastic; epigenetics; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; tissue array analysis; salivary gland neoplasms; dna mutational analysis; adenoid cystic carcinoma; carcinoma, adenoid cystic; nonsense mutation; notch1 receptor; cyclic amp dependent protein kinase; mucin 4; indel mutation; brm protein; genetic association studies; protein myb; exome; ankyrin; xeroderma pigmentosum group d protein; crebbp protein; dnah11 protein; kdm6a protein; mucin 16; transcription factor foxp2; splicing mutation
Journal Title: Nature Genetics
Volume: 45
Issue: 7
ISSN: 1061-4036
Publisher: Nature Publishing Group  
Date Published: 2013-07-01
Start Page: 791
End Page: 798
Language: English
DOI: 10.1038/ng.2643
PROVIDER: scopus
PMCID: PMC3708595
PUBMED: 23685749
DOI/URL:
Notes: --- - "Export Date: 1 August 2013" - "CODEN: NGENE" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Adriana Heguy
    85 Heguy
  2. Timothy Chan
    221 Chan
  3. Stella Lee Eng
    6 Eng
  4. Bhuvanesh Singh
    206 Singh
  5. Nora Katabi
    156 Katabi
  6. Luc Morris
    125 Morris
  7. Jason T Huse
    127 Huse
  8. Agnes Viale
    205 Viale
  9. Ian Ganly
    231 Ganly
  10. Yongxing Gong
    7 Gong
  11. Sevin Turcan
    25 Turcan
  12. Chris Sander
    196 Sander
  13. Rileen Sinha
    19 Sinha
  14. Jatin P Shah
    542 Shah
  15. Logan Alexander Walsh
    19 Walsh
  16. Kasthuri Srinivasan Kannan
    11 Kannan
  17. Allen Szu Hao Ho
    17 Ho
  18. Nikolaus D Schultz
    202 Schultz
  19. Benjamin E Gross
    26 Gross
  20. Christine Elizabeth Rice
    3 Rice
  21. Yupu Liang
    8 Liang
  22. William Lee
    38 Lee
  23. David Matthew Roy
    7 Roy
  24. Jianan Zhang
    7 Zhang
  25. Luke C Peng
    3 Peng