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题目:: Targeted next-generation sequencing of head and neck squamous cell carcinoma identifies novel genetic alterations in HPV+ and HPV- tumors.
作者:: Lechner(Matthias),Frampton(Garrett M),Fenton(Tim),Feber(Andrew),Palmer(Gary),Jay(Amrita),Pillay(Nischalan),Forster(Martin),Cronin(Maureen T),Lipson(Doron),Miller(Vincent A),Brennan(Timothy A),Henderson(Stephen),Vaz(Francis),O'Flynn(Paul),Kalavrezos(Nicholas),Yelensky(Roman),Beck(Stephan),Stephens(Philip J),Boshoff(Chris)
状态:: 发布时间2014-08-12 , 更新时间 2015-08-12
期刊:: Genome Med
摘要:: Human papillomavirus positive (HPV+) head and neck squamous cell carcinoma (HNSCC) is an emerging disease, representing a distinct clinical and epidemiological entity. Understanding the genetic basis of this specific subtype of cancer could allow therapeutic targeting of affected pathways for a stratified medicine approach.,Twenty HPV+ and 20 HPV- laser-capture microdissected oropharyngeal carcinomas were used for paired-end sequencing of hybrid-captured DNA, targeting 3,230 exons in 182 genes often mutated in cancer. Copy number alteration (CNA) profiling, Sequenom MassArray sequencing and immunohistochemistry were used to further validate findings.,HPV+ and HPV- oropharyngeal carcinomas cluster into two distinct subgroups. TP53 mutations are detected in 100% of HPV negative cases and abrogation of the G1/S checkpoint by CDKN2A/B deletion and/or CCND1 amplification occurs in the majority of HPV- tumors.,These findings strongly support a causal role for HPV, acting via p53 and RB pathway inhibition, in the pathogenesis of a subset of oropharyngeal cancers and suggest that studies of CDK inhibitors in HPV- disease may be warranted. Mutation and copy number alteration of PI3 kinase (PI3K) pathway components appears particularly prevalent in HPV+ tumors and assessment of these alterations may aid in the interpretation of current clinical trials of PI3K, AKT, and mTOR inhibitors in HNSCC.
语言:: eng
DOI:

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