title: Genetic Mutation and Exosome Signature of Human Papilloma Virus Associated Oropharyngeal Cancer.
abstract: Human papilloma virus-16 (HPV-16) associated oropharyngeal cancer (HPVOPC) is increasing alarmingly in the United States. We performed whole genome sequencing of a 44 year old, male HPVOPC subject diagnosed with moderately differentiated tonsillar carcinoma. We identified new somatic mutation in MUC16 (A.k.a. CA-125), MUC12, MUC4, MUC6, MUC2, SIRPA, HLA-DRB1, HLA-A and HLA-B molecules. Increased protein expression of MUC16, SIRPA and decreased expression of HLA-DRB1 was further demonstrated in this HPVOPC subject and an additional set of 15 HPVOPC cases. Copy number gain (3 copies) was also observed for MUC2, MUC4, MUC6 and SIRPA. Enhanced expression of MUC16, SIRPA and HPV-16-E7 protein was detectable in the circulating exosomes of numerous HPVOPC subjects. Treatment of non-tumorigenic mammary epithelial cells with exosomes derived from aggressive HPVOPC cells harboring MUC16, SIRPA and HPV-16-E7 proteins augmented invasion and induced epithelial to mesenchymal transition (EMT) accompanied by an increased expression ratio of the EMT markers Vimentin/E-cadherin. Exosome based screening of key HPVOPC associated molecules could be beneficial for early cancer diagnosis, monitoring and surveillance.
authors.affiliation: Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, Texas, USA.
authors.forename: Anbarasu
authors.initials: A
authors.lastname: Kannan
authors.affiliation: Department of Biology, The University of Texas at Tyler, Tyler, Texas, USA.
authors.forename: Kate L
authors.initials: KL
authors.lastname: Hertweck
authors.affiliation: Department of Medicine, The University of Texas Health Science Center at Tyler, Tyler, Texas, USA.
authors.forename: Julie V
authors.initials: JV
authors.lastname: Philley
authors.affiliation: Department of Pathology, The University of Texas Health Science Center at Tyler, Tyler, Texas., USA.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Wells
authors.affiliation: Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, Texas, USA.
authors.forename: Santanu
authors.initials: S
authors.lastname: Dasgupta
mesh_terms: D000328:Adult; D056915:DNA Copy Number Variations / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition; D055354:Exosomes / Q000378:metabolism*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D052162:Human papillomavirus 16 / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009959:Oropharyngeal Neoplasms / Q000473:pathology / Q000821:virology*; D027383:Papillomaviridae / Q000235:genetics*; D015203:Reproducibility of Results
chemical_list: D009363:Neoplasm Proteins