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Comprehensive genomic characterization of squamous cell lung cancers

Author(s)
Park, Peter J.; Lander, Eric Steven
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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.
Date issued
2012-09
URI
http://hdl.handle.net/1721.1/84671
Department
Massachusetts Institute of Technology. Department of Biology
Journal
Nature
Publisher
Nature Publishing Group
Citation
Hammerman, Peter S., Michael S. Lawrence, Douglas Voet, Rui Jing, Kristian Cibulskis, Andrey Sivachenko, Petar Stojanov, et al. “Comprehensive genomic characterization of squamous cell lung cancers.” Nature 489, no. 7417 (September 9, 2012): 519-525.
Version: Final published version
ISSN
0028-0836
1476-4687

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