%0 Journal Article
%T A Pilot Study Comparing HPV-Positive and HPV-Negative Head and Neck Squamous Cell Carcinomas by Whole Exome Sequencing
%A Anthony C. Nichols
%A Michelle Chan-Seng-Yue
%A John Yoo
%A Wei Xu
%A Sandeep Dhaliwal
%A John Basmaji
%A Christopher C. T. Szeto
%A Samuel Dowthwaite
%A Biljana Todorovic
%A Maud H. W. Starmans
%A Philippe Lambin
%A David A. Palma
%A Kevin Fung
%A Jason H. Franklin
%A Bret Wehrli
%A Keith Kwan
%A James Koropatnick
%A Joe S. Mymryk
%A Paul Boutros
%A John W. Barrett
%J ISRN Oncology
%D 2012
%R 10.5402/2012/809370
%X 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. 1. Introduction Tobacco use has steadily declined over the last four decades [1]. In parallel, there has been a decline in cancers of most sites in the upper aerodigestive tract [2]. The exception to this trend is cancers of the oropharynx, particularly those of the palatine and lingual tonsils, which are caused by oncogenic subtypes of the human papillomavirus (HPV) [3]. The rise in incidence of HPV-positive head and neck squamous cell carcinoma (HNSCC) has been dramatic, causing the rates of tonsillar cancer to increase by as much as threefold in some countries [3, 4]. HPV-positive patients experience markedly better survival, and their tumors are molecularly distinct from traditional head and neck cancers [5]. Overexpression of p16 and proteolysis of p53 are nearly universal in HPV-positive tumors, in contrast to frequent loss of p16 and point mutations in p53 that are found in HPV-negative cancers [5]. However, the specific mechanisms responsible for improved survival in HPV-positive patients have not been fully elucidated. Next-generation sequencing has yielded important insights into the pathogenesis of other cancers by identifying biomarkers and therapeutic targets. High-throughput sequencing of HNSCC tumors has recently been reported, and NOTCH inactivation was the most significant finding [6, 7]. This pilot study aims to contrast the mutations seen in an HPV-positive and an HPV-negative tumor using whole exome sequencing and
%U http://www.hindawi.com/journals/isrn.oncology/2012/809370/