采用新一代测序技术分析头颈部鳞状细胞癌的分子异质性 Am J Pathol. 2014,84(5):1323-30.
依据与高危亚型人类乳头状瘤病毒（HPV16 and HPV18）的相关性，头颈部鳞状细胞癌（HNSCC）被分为两种不同的临床亚型组。近年来，在某种程度上由于与HPV感染有关的HNSCC在逐渐增加，且其在预后和分子组学方面的差异性引起了学者们的注意，然而，如何分类这些肿瘤，其潜在的作用机制和详尽的基因组学仍然没有被阐明。为了阐明伴和不伴HPV感染的HNSCC致癌途径，我们采用定向的新一代测序技术来检测50个癌相关基因的单核苷酸多态性（SNPs），在伴和不伴HPV感染的HNSCC组织标本中，我们发现其中有25个基因（25/50）可以检测到SNPs；在这25个基因中，有5个基因无论有无HPV感染，其变异模式是相似的。基因从酪氨酸蛋白激酶受体和其相关通路中，较大数量的序列变异优先出现在HPV+的标本中。在基因相关肿瘤抑制功能方面，SNPs普遍存在HPV-的HNSCC标本中。这些观察结果可能帮助我们阐明两种临床上不同亚型HNSCC的具体分子发病机制。无论是HPV+，还是HPV-的HNSCC，SNPs的过度表现可能成为靶向治疗HNSCC的潜在变异序列。


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 polymorphisms (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 þ 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 þ or HPV HNSCC is another indicator of potentially actionable sequence variants for targeted therapy.(Am J Pathol 2014, 184: 1323e1330;http://dx.doi.org/10.1016/j.ajpath.2014.01.028)