Molecular Heterogeneity of Head and Neck Squamous Cell Carcinoma Defined by Next-Generation Sequencing
Molecular Heterogeneity of Head and Neck Squamous Cell Carcinoma Defined by Next-Generation Sequencing
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DOI：
10.1016/j.ajpath.2014.01.028
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发表时间：
2014-05-01
影响因子：
6
通讯作者：
Fernandes, Helen
中科院分区：
文献类型：
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作者：
Zhang, Pan;Mirani, Neena;Fernandes, Helen
头颈部鳞状细胞癌（HNSCC）可根据其与人乳头状瘤病毒（HPV 16和HPV 18）高危亚型的相关性分为两种不同的临床实体。近年来，预后和分子特征的差异引起了人们的广泛关注，部分原因是HNSCC中HPV感染率的增加;然而，将这些肿瘤分开的潜在机制和详细的遗传特征仍然难以捉摸。为了阐明伴和不伴HPV感染的HNSCC中的致癌途径，我们使用靶向下一代测序来询问50个癌症相关基因中的单核苷酸多态性（SNP）。我们在有和没有HPV感染的HNSCC组织标本中检测了25个这些基因的SNP。在25个基因中的5个中，无论HPV感染状态如何，变异模式都是相似的。更多的序列变异的基因从酪氨酸激酶受体及其相关的途径，优先存在于HPV+标本。与肿瘤抑制功能相关的基因中的SNP在HPV-HNSCC标本中更普遍。这些观察可能有助于阐明两种临床上不同的HNSCC亚类的分子发病机制。SNP在HPV+或HPV-HNSCC中的过表达是用于靶向治疗的潜在可行序列变体的另一个指标。
Head and neck squamous cell carcinoma (HNSCC) can be divided into two different clinical entities based on their association with high-risk subtypes of human papilloma virus (HPV16 and HPV18). Dissimilarities in prognosis and molecular profiles have attracted much attention in recent years, in part because of increasing rates of HPV infection in HNSCC; however, the underlying mechanisms and detailed genetic profiles that set these tumors apart are still elusive. To elucidate oncogenic pathways in HNSCC with and without HPV infection, we used targeted next-generation sequencing to interrogate single-nucleotide potymorphisms (SNPs) in 50 cancer-related genes. We detected SNPs in 25 of these genes from HNSCC tissue specimens with and without HPV infection. In 5 of the 25 genes, variant patterns were similar regardless of HPV infection status. A greater number of sequence variants in genes from the tyrosine kinase receptors and their associated pathways were preferentially present in HPV+ specimens. SNPs in genes related to tumor-suppressor functions were more prevalent in HPV- HNSCC specimens. The observations may help to elucidate mechanisms involved in the molecular pathogenesis of two clinically diverse subclasses of HNSCC. Over-representation of SNPs in either HPV+ or HPV- HNSCC is another indicator of potentially actionable sequence variants for targeted therapy.