Comprehensive genomic characterization of squamous cell lung cancers
Комплексная геномная характеристика плоскоклеточного рака лёгкого
2012-09-07
SCID: 54.1/q8nkjvnr
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TP53 mutationsThe Cancer Genome Atlasepigenomic alterationsgenomic alterationslung squamous cell carcinoma
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Abstract (AI)
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. 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.
Key Findings
1
A potential therapeutic target was identified in most tumors, providing new avenues for targeted treatment research despite the absence of specifically developed molecular therapies.
2
Major altered pathways included NFE2L2/KEAP1 in 34%, squamous differentiation genes in 44%, the phosphatidylinositol-3-OH kinase pathway in 47%, and CDKN2A/RB1 in 72% of tumors.
3
Statistically recurrent mutations occurred in 11 genes, with TP53 mutated in nearly all specimens; loss-of-function mutations were also identified in HLA-A.
4
The Cancer Genome Atlas profiled 178 lung squamous cell carcinomas, establishing a comprehensive genomic and epigenomic alteration landscape.
5
Tumors exhibited substantial genomic complexity, averaging 360 exonic mutations, 165 genomic rearrangements, and 323 copy-number alteration segments per tumor.
Research Object
178 lung squamous cell carcinomas
Research Subject
The comprehensive landscape and recurrent patterns of genomic and epigenomic alterations, including mutations, genomic rearrangements, copy-number alterations, and pathway disruptions
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2012-09-07
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