Targeted next-generation sequencing of head and neck squamous cell carcinoma identifies novel genetic alterations in HPV+ and HPV- tumors.
Targeted next-generation sequencing of head and neck squamous cell carcinoma identifies novel genetic alterations in HPV+ and HPV- tumors.
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靶向的头部和颈部鳞状细胞癌的下一代测序鉴定了HPV+和HPV-肿瘤中的新遗传改变。
DOI：
10.1186/gm453
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发表时间：
2013
期刊：
影响因子：
12.3
通讯作者：
Boshoff C
中科院分区：
文献类型：
--
作者：
Lechner M;Frampton GM;Fenton T;Feber A;Palmer G;Jay A;Pillay N;Forster M;Cronin MT;Lipson D;Miller VA;Brennan TA;Henderson S;Vaz F;O'Flynn P;Kalavrezos N;Yelensky R;Beck S;Stephens PJ;Boshoff C
人乳头瘤病毒阳性(HPV+)头颈部鳞状细胞癌(HNSCC)是一种新出现的疾病，具有独特的临床和流行病学特征。了解这一特定癌症亚型的遗传基础可以为分层医学方法提供针对受影响路径的治疗靶点。20个HPV+和20个HPV激光捕获的口咽癌显微解剖标本用于杂交捕获的DNA的双端测序，目标是182个在癌症中经常突变的基因的3230个外显子。采用拷贝数改变(CNA)分析、Sequenom Massarray测序和免疫组织化学方法进一步验证研究结果。HPV+和HPV-口咽癌分为两个不同的亚组。Tp53基因突变在100%的HPV阴性病例中被检测到，并且在大多数HPV阴性的肿瘤中，通过CDKN2A/B缺失和/或CCND1DNA扩增消除了G1/S检查点。这些发现有力地支持了HPV通过抑制P53和Rb通路在口咽癌亚组的发病机制中的因果作用，并表明CDK抑制剂在HPV疾病中的研究可能是有必要的。PI3K途径组分的突变和拷贝数改变在HPV+肿瘤中尤为普遍，对这些改变的评估可能有助于解释目前PI3K、AKT和mTOR抑制剂在HNSCC中的临床试验。
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.
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使用下一代 DNA 测序数据进行变异发现和基因分型的框架。
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
12.3
作者：
Lechner M;Fenton T;West J;Wilson G;Feber A;Henderson S;Thirlwell C;Dibra HK;Jay A;Butcher L;Chakravarthy AR;Gratrix F;Patel N;Vaz F;O'Flynn P;Kalavrezos N;Teschendorff AE;Boshoff C;Beck S
通讯作者：
Beck S
影响因子：
14.9
作者：
Forbes SA;Bindal N;Bamford S;Cole C;Kok CY;Beare D;Jia M;Shepherd R;Leung K;Menzies A;Teague JW;Campbell PJ;Stratton MR;Futreal PA
通讯作者：
Futreal PA
影响因子：
3.9
作者：
Petitjean, Audrey;Mathe, Ewy;Olivier, Magali
通讯作者：
Olivier, Magali
影响因子：
3.7
作者：
Freier, Koija;Knoepfle, Karl;Radwirnmer, Bernhard
通讯作者：
Radwirnmer, Bernhard