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Comprehensive genomic characterization of squamous cell lung cancers
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Journal Article
Comprehensive genomic characterization of squamous cell lung cancers
2012
Overview
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.
Comprehensive analyses of 178 lung squamous cell carcinomas by The Cancer Genome Atlas project show that the tumour type is characterized by complex genomic alterations, with statistically recurrent mutations in 11 genes, including
TP53
in nearly all samples; a potential therapeutic target is identified in most of the samples studied.
Lung-cancer genomes analysed
The Cancer Genome Atlas consortium has analysed 178 lung squamous cell carcinomas, a common type of lung cancer for which comprehensive genomic analyses have not previously been available. The researchers report that this tumour type is characterized by complex genomic alterations, with recurrent mutations in 18 genes, including
TP53
in nearly all samples. They also report frequent mutations in squamous differentiation genes. Collectively, these analyses identify potential therapeutic targets worthy of further investigation.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Adenocarcinoma - drug therapy
/ Biological and medical sciences
/ Carcinoma, Squamous Cell - drug therapy
/ Carcinoma, Squamous Cell - genetics
/ Carcinoma, Squamous Cell - metabolism
/ Gene Expression Regulation, Neoplastic
/ Genetics
/ Genomes
/ Genomics
/ Humanities and Social Sciences
/ Humans
/ Kinases
/ Lung Neoplasms - drug therapy
/ Mutation
/ Phosphatidylinositol 3-Kinases - metabolism
/ Science
/ Signal Transduction - genetics
/ Tumors
