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Reporter: Aviva Lev-Ari, PhD, RN

Comprehensive genomic characterization of squamous cell lung cancer

Nature (2012) doi:10.1038/nature11404

Received 09 March 2012 
Accepted 09 July 2012 
Published online 09 September 2012

 

 

Correspondence to: 

The primary and processed data used to generate the analyses presented here can be downloaded by registered users fromThe Cancer Genome Atlas (https://tcga-data.nci.nih.gov/tcga/tcgaDownload.jsp,https://cghub.ucsc.edu/ and https://tcga-data.nci.nih.gov/docs/publications/lusc_2012/).

 

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 andKEAP1 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.

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