一项通过全外显子组测序比较HPV阳性和HPV阴性头颈部鳞状细胞癌的初步研究。
A Pilot Study Comparing HPV-Positive and HPV-Negative Head and Neck Squamous Cell Carcinomas by Whole Exome Sequencing.
作者信息
Nichols Anthony C, Chan-Seng-Yue Michelle, Yoo John, Xu Wei, Dhaliwal Sandeep, Basmaji John, Szeto Christopher C T, Dowthwaite Samuel, Todorovic Biljana, Starmans Maud H W, Lambin Philippe, Palma David A, Fung Kevin, Franklin Jason H, Wehrli Bret, Kwan Keith, Koropatnick James, Mymryk Joe S, Boutros Paul, Barrett John W
机构信息
Department of Otolaryngology-Head and Neck Surgery, Western University, Victoria Hospital, London Health Science Centre, Room B3-431A, 800 Commissioners Road East, London, ON, Canada N6A 5W9 ; London Regional Cancer Program, London, ON, Canada N6A 4L6 ; Lawson Health Research Institute, London, ON, Canada N6C 2R5 ; Department of Oncology, Western University, London, ON, Canada N6A 4L6 ; Department of Pathology, Western University, London, ON, Canada N6A 5C1.
出版信息
ISRN Oncol. 2012;2012:809370. doi: 10.5402/2012/809370. Epub 2012 Dec 12.
Background. Next-generation sequencing of cancers has identified important therapeutic targets and biomarkers. The goal of this pilot study was to compare the genetic changes in a human papillomavirus- (HPV-)positive and an HPV-negative head and neck tumor. Methods. DNA was extracted from the blood and primary tumor of a patient with an HPV-positive tonsillar cancer and those of a patient with an HPV-negative oral tongue tumor. Exome enrichment was performed using the Agilent SureSelect All Exon Kit, followed by sequencing on the ABI SOLiD platform. Results. Exome sequencing revealed slightly more mutations in the HPV-negative tumor (73) in contrast to the HPV-positive tumor (58). Multiple mutations were noted in zinc finger genes (ZNF3, 10, 229, 470, 543, 616, 664, 638, 716, and 799) and mucin genes (MUC4, 6, 12, and 16). Mutations were noted in MUC12 in both tumors. Conclusions. HPV-positive HNSCC is distinct from HPV-negative disease in terms of evidence of viral infection, p16 status, and frequency of mutations. Next-generation sequencing has the potential to identify novel therapeutic targets and biomarkers in HNSCC.
背景。癌症的下一代测序已确定了重要的治疗靶点和生物标志物。本初步研究的目的是比较人乳头瘤病毒（HPV）阳性和HPV阴性头颈部肿瘤的基因变化。方法。从一名HPV阳性扁桃体癌患者的血液和原发肿瘤以及一名HPV阴性舌癌患者的血液和原发肿瘤中提取DNA。使用安捷伦SureSelect全外显子试剂盒进行外显子富集，随后在ABI SOLiD平台上进行测序。结果。外显子测序显示，与HPV阳性肿瘤（58个）相比，HPV阴性肿瘤（73个）的突变略多。在锌指基因（ZNF3、10、229、470、543、616、664、638、716和799）和粘蛋白基因（MUC4、6、12和16）中发现了多个突变。在两种肿瘤的MUC12中均发现了突变。结论。HPV阳性的头颈部鳞状细胞癌在病毒感染证据、p16状态和突变频率方面与HPV阴性疾病不同。下一代测序有潜力在头颈部鳞状细胞癌中识别新的治疗靶点和生物标志物。
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