Genetic Mutation and Exosome Signature of Human Papilloma Virus Associated Oropharyngeal Cancer

Anbarasu Kannan, Kate L. Hertweck, Julie V. Philley, Robert B. Wells, Santanu Dasgupta

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number46102
JournalScientific Reports
Volume7
DOIs
StatePublished - Apr 6 2017
Externally publishedYes

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Oropharyngeal Neoplasms
Exosomes
Papilloma
Viruses
Mutation
Human papillomavirus 16
Proteins
HLA-DRB1 Chains
Epithelial-Mesenchymal Transition
HLA-A Antigens
HLA-B Antigens
Vimentin
Cadherins
Early Detection of Cancer
Breast
Epithelial Cells
Genome
Carcinoma

ASJC Scopus subject areas

  • General

Cite this

Genetic Mutation and Exosome Signature of Human Papilloma Virus Associated Oropharyngeal Cancer. / Kannan, Anbarasu; Hertweck, Kate L.; Philley, Julie V.; Wells, Robert B.; Dasgupta, Santanu.

In: Scientific Reports, Vol. 7, 46102, 06.04.2017.

Research output: Contribution to journalArticle

Kannan, Anbarasu; Hertweck, Kate L.; Philley, Julie V.; Wells, Robert B.; Dasgupta, Santanu / Genetic Mutation and Exosome Signature of Human Papilloma Virus Associated Oropharyngeal Cancer.

In: Scientific Reports, Vol. 7, 46102, 06.04.2017.

Research output: Contribution to journalArticle

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