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Comprehensive genomic characterization of squamous cell lung cancers

2012· article· en· 4 016 citations· W2275877493 sur OpenAlex· 10.1038/nature11404

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Résumé

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.

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La notice

Revue
Nature
Thématique
Cancer Genomics and Diagnostics
Domaine
Biochemistry, Genetics and Molecular Biology
Établissements canadiens
Kensington HealthOttawa HospitalOntario Institute for Cancer ResearchCanada's Michael Smith Genome Sciences Centre
Organismes subventionnaires
National Cancer InstituteNational Human Genome Research InstituteBC Cancer AgencyNational Institutes of Health
Mots-clés
CDKN2ACancer researchBiologyLung cancerPTENEpigenomicsComparative genomic hybridizationCancerGenePathologyGenomeMedicineGeneticsPI3K/AKT/mTOR pathwaySignal transductionDNA methylationGene expression
Résumé présent dans OpenAlex
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