Analysis of Human Papilloma Virus Content and Integration in Mucoepidermoid Carcinoma

Wenjin Gu; Apurva Bhangale; Molly E. Heft Neal; Josh D. Smith; Collin Brummel; Jonathan B. McHugh; Matthew E. Spector; Ryan E. Mills; J. Chad Brenner

doi:10.3390/v14112353

Viruses (Oct 2022)

Analysis of Human Papilloma Virus Content and Integration in Mucoepidermoid Carcinoma

Wenjin Gu,
Apurva Bhangale,
Molly E. Heft Neal,
Josh D. Smith,
Collin Brummel,
Jonathan B. McHugh,
Matthew E. Spector,
Ryan E. Mills,
J. Chad Brenner

Affiliations

Wenjin Gu: Department of Bioinformatics and Computational Biology, University of Michigan, Ann Arbor, MI 48109, USA
Apurva Bhangale: Department of Otolaryngology–Head and Neck Surgery, University of Michigan, Ann Arbor, MI 48109, USA
Molly E. Heft Neal: Department of Otolaryngology–Head and Neck Surgery, University of Michigan, Ann Arbor, MI 48109, USA
Josh D. Smith: Department of Otolaryngology–Head and Neck Surgery, University of Michigan, Ann Arbor, MI 48109, USA
Collin Brummel: Department of Otolaryngology–Head and Neck Surgery, University of Michigan, Ann Arbor, MI 48109, USA
Jonathan B. McHugh: Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA
Matthew E. Spector: Rogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA
Ryan E. Mills: Department of Bioinformatics and Computational Biology, University of Michigan, Ann Arbor, MI 48109, USA
J. Chad Brenner: Department of Otolaryngology–Head and Neck Surgery, University of Michigan, Ann Arbor, MI 48109, USA

DOI: https://doi.org/10.3390/v14112353
Journal volume & issue: Vol. 14, no. 11
p. 2353

Abstract

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Mucoepidermoid Carcinomas (MEC) represent the most common malignancies of salivary glands. Approximately 50% of all MEC cases are known to harbor CRTC1/3-MAML2 gene fusions, but the additional molecular drivers remain largely uncharacterized. Here, we sought to resolve controversy around the role of human papillomavirus (HPV) as a potential driver of mucoepidermoid carcinoma. Bioinformatics analysis was performed on 48 MEC transcriptomes. Subsequent targeted capture DNA sequencing was used to annotate HPV content and integration status in the host genome. HPV of any type was only identified in 1/48 (2%) of the MEC transcriptomes analyzed. Importantly, the one HPV16+ tumor expressed high levels of p16, had high expression of HPV16 oncogenes E6 and E7, and displayed a complex integration pattern that included breakpoints into 13 host genes including PIK3AP1, HIPI, OLFM4,SIRT1, ARAP2, TMEM161B-AS1, and EPS15L1 as well as 9 non-genic regions. In this cohort, HPV is a rare driver of MEC but may have a substantial etiologic role in cases that harbor the virus. Genetic mechanisms of host genome integration are similar to those observed in other head and neck cancers.

Published in Viruses

ISSN: 1999-4915 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Microbiology
Website: http://www.mdpi.com/journal/viruses

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Abstract

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