Comprehensive genomic characterization of squamous cell lung cancers Journal Article


Author: The Cancer Genome Atlas Research Network
Contributors: Socci, N. D.; Liang, Y.; Schultz, N.; Borsu, L.; Lash, A. E.; Viale, A.; Sander, C.; Ladanyi, M.; Sinha, R.; Ciriello, G.; Cerami, E.; Gross, B.; Jacobsen, A.; Gao, J.; Aksoy, B. A.; Weinhold, N.; Ramirez, R.; Taylor, B. S.; Antipin, Y.; Reva, B.; Shen, R.; Mo, Q.; Seshan, V.; Paik, P. K.; Travis, W. D.; Rekhtman, N.; Rusch, V.; Zakowski, M.
Article Title: Comprehensive genomic characterization of squamous cell lung cancers
Abstract: Lung squamous cell carcinoma is a common type of lung cancer, causing approximately 400,000 deaths per year worldwide. Genomic alterations in squamous cell lung cancers have not been comprehensively characterized, and no molecularly targeted agents have been specifically developed for its treatment. As part of The Cancer Genome Atlas, here we profile 178 lung squamous cell carcinomas to provide a comprehensive landscape of genomic and epigenomic alterations. We show that the tumour type is characterized by complex genomic alterations, with a mean of 360 exonic mutations, 165 genomic rearrangements, and 323 segments of copy number alteration per tumour. We find statistically recurrent mutations in 11 genes, including mutation of TP53 in nearly all specimens. Previously unreported loss-of-function mutations are seen in the HLA-A class I major histocompatibility gene. Significantly altered pathways included NFE2L2 and KEAP1 in 34%, squamous differentiation genes in 44%, phosphatidylinositol-3-OH kinase pathway genes in 47%, and CDKN2A and RB1 in 72% of tumours. We identified a potential therapeutic target in most tumours, offering new avenues of investigation for the treatment of squamous cell lung cancers. © 2012 Macmillan Publishers Limited. All rights reserved.
Keywords: controlled study; human tissue; major clinical study; exon; mutation; mortality; cytology; enzyme activity; phosphatidylinositol 3 kinase; protein p53; genetic engineering; epigenetics; hla antigen class 1; genomics; lung squamous cell carcinoma; cyclin dependent kinase inhibitor 2a; tumor; major histocompatibility complex; loss of function mutation; medicine; disease treatment; copy number variation; kelch like ech associated protein 1
Journal Title: Nature
Volume: 489
Issue: 7417
ISSN: 0028-0836
Publisher: Nature Publishing Group  
Date Published: 2012-09-27
Start Page: 519
End Page: 525
Language: English
DOI: 10.1038/nature11404
PROVIDER: scopus
PMCID: PMC3466113
PUBMED: 22960745
DOI/URL:
Notes: --- - "Export Date: 2 November 2012" - "CODEN: NATUA" - "Source: Scopus"
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MSK Authors
  1. Venkatraman Ennapadam Seshan
    294 Seshan
  2. Qianxing Mo
    37 Mo
  3. Natasha Rekhtman
    220 Rekhtman
  4. Valerie W Rusch
    671 Rusch
  5. Ronglai Shen
    131 Shen
  6. Marc Ladanyi
    897 Ladanyi
  7. William D Travis
    554 Travis
  8. Maureen F Zakowski
    281 Zakowski
  9. Paul K Paik
    90 Paik
  10. Agnes Viale
    208 Viale
  11. Boris A Reva
    36 Reva
  12. Alex E Lash
    24 Lash
  13. Nicholas D Socci
    189 Socci
  14. Chris Sander
    196 Sander
  15. Rileen Sinha
    19 Sinha
  16. Jianjiong Gao
    66 Gao
  17. Barry Stephen Taylor
    150 Taylor
  18. Ethan Cerami
    21 Cerami
  19. Nikolaus D Schultz
    213 Schultz
  20. Benjamin E Gross
    28 Gross
  21. Yevgeniy Antipin
    19 Antipin
  22. Yupu Liang
    8 Liang
  23. Bulent Arman Aksoy
    33 Aksoy
  24. Ricardo   Ramirez
    19 Ramirez