2015
DOI: 10.1038/nature14129
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Abstract: The Cancer Genome Atlas profiled 279 head and neck squamous cell carcinomas (HNSCCs) to provide a comprehensive landscape of somatic genomic alterations. We find that human papillomavirus-associated (HPV) tumors are dominated by helicase domain mutations of the oncogene PIK3CA, novel alterations involving loss of TRAF3, and amplification of the cell cycle gene E2F1. Smoking-related HNSCCs demonstrate near universal loss of TP53 mutations and CDKN2A with frequent copy number alterations including a novel amplif… Show more

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Cited by 3,085 publications
(2,822 citation statements)
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“…The advent and improvements in massively parallel (next generation) sequencing and other array based methods during the past decade have made possible the comprehensive multi‐platform TCGA and several large‐scale studies defining the landscape of genomic and epigenetic alterations in HNSCC 2, 3, 4, 5, 6, 9. Globally, most HNSCC harbor complex chromosomal rearrangements, among which there are common and less frequent recurrent alterations that have been associated with HPV status, malignant phenotype, outcome, and certain gene(s) that are of potential clinical significance.…”
Section: Resultsmentioning
confidence: 99%
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“…The advent and improvements in massively parallel (next generation) sequencing and other array based methods during the past decade have made possible the comprehensive multi‐platform TCGA and several large‐scale studies defining the landscape of genomic and epigenetic alterations in HNSCC 2, 3, 4, 5, 6, 9. Globally, most HNSCC harbor complex chromosomal rearrangements, among which there are common and less frequent recurrent alterations that have been associated with HPV status, malignant phenotype, outcome, and certain gene(s) that are of potential clinical significance.…”
Section: Resultsmentioning
confidence: 99%
“…Higher mutation frequency is considered a factor in generation of neoantigens necessary for immune recognition and response to new immune checkpoint therapies. In addition to CpG transversions commonly attributed to tobacco carcinogen DNA adducts expected in HPV(‐) tumors, HPV (‐) and (+) HNSCC also display mutations within TpC dinucleotides linked to deregulation of APOBEC cytosine deaminases that repair altered bases 3. These mutations affect certain motifs of relevance to recurrent mutation “hotspots” that can enhance function and potential sensitivity to therapeutics targeting particular oncogenic signal kinases.…”
Section: Resultsmentioning
confidence: 99%
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