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Nature DOI:10.1038/nature11404

Comprehensive genomic characterization of squamous cell lung cancers.

Publication TypeJournal Article
Year of Publication2012
Corporate AuthorsCancer Genome Atlas Research Network
JournalNature
Volume489
Issue7417
Pages519-25
Date Published2012 Sep 27
ISSN1476-4687
KeywordsAdenocarcinoma, Carcinoma, Squamous Cell, DNA Mutational Analysis, Gene Deletion, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Genes, p16, Genes, p53, Genome, Human, Genomics, Humans, Lung Neoplasms, Molecular Targeted Therapy, Mutation, Mutation Rate, Phosphatidylinositol 3-Kinases, Signal Transduction
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.

URLhttp://dx.doi.org/10.1038/nature11404
DOI10.1038/nature11404
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/22960745?dopt=Abstract

Alternate JournalNature
PubMed ID22960745
PubMed Central IDPMC3466113
Grant ListP30 CA016672 / CA / NCI NIH HHS / United States
U24 CA143882 / CA / NCI NIH HHS / United States
U54 HG003067 / HG / NHGRI NIH HHS / United States
U24 CA143835 / CA / NCI NIH HHS / United States
K08 CA137153 / CA / NCI NIH HHS / United States
R01 CA094143 / CA / NCI NIH HHS / United States
U24 CA143866 / CA / NCI NIH HHS / United States
U24 CA126551 / CA / NCI NIH HHS / United States
P30 CA016086 / CA / NCI NIH HHS / United States
U24 CA143845 / CA / NCI NIH HHS / United States
U24 CA143799 / CA / NCI NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
T32 CA009172 / CA / NCI NIH HHS / United States
U24 CA144025 / CA / NCI NIH HHS / United States
U24 CA126554 / CA / NCI NIH HHS / United States
U24 CA143840 / CA / NCI NIH HHS / United States
U24 CA143843 / CA / NCI NIH HHS / United States
U24 CA126561 / CA / NCI NIH HHS / United States
U24 CA143858 / CA / NCI NIH HHS / United States
R01 HG006272 / HG / NHGRI NIH HHS / United States
U24 CA143848 / CA / NCI NIH HHS / United States
U24 CA126543 / CA / NCI NIH HHS / United States
U54 HG003079 / HG / NHGRI NIH HHS / United States
R00 CA149182 / CA / NCI NIH HHS / United States
R01 CA149569 / CA / NCI NIH HHS / United States
U24 CA143883 / CA / NCI NIH HHS / United States
U24 CA143867 / CA / NCI NIH HHS / United States
U24 CA126546 / CA / NCI NIH HHS / United States
P01 CA129243 / CA / NCI NIH HHS / United States
U24 CA126563 / CA / NCI NIH HHS / United States
U24 CA126544 / CA / NCI NIH HHS / United States