Analysis of Human Papilloma Virus Content and Integration in Mucoepidermoid Carcinoma

Mucoepidermoid Carcinomas (MEC) represent the most common malignancies of salivary glands. Approximately 50% of all MEC cases are known to harbor gene fusions, but the additional molecular drivers remain largely uncharacterized. Here, we sought to resolve controversy around the role of human papillo...

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Bibliographic Details
Published in:Viruses 2022-10, Vol.14 (11), p.2353
Main Authors: Gu, Wenjin, Bhangale, Apurva, Heft Neal, Molly E, Smith, Josh D, Brummel, Collin, McHugh, Jonathan B, Spector, Matthew E, Mills, Ryan E, Brenner, J Chad
Format: Article
Language:English
Subjects:
Alphapapillomavirus
Analysis
Archives & records
Bioinformatics
Breakpoints
Carcinoma
Carcinoma, Mucoepidermoid - genetics
Carcinoma, Mucoepidermoid - metabolism
Carcinoma, Mucoepidermoid - pathology
CRTC1/3-MAML2
Development and progression
DNA sequencing
DNA-Binding Proteins - genetics
Exocrine glands
Gene expression
Genomes
Head & neck cancer
HPV
Human papillomavirus
Humans
Integration
Malignancy
MEC
Medical records
Nuclear Proteins - genetics
Papillomaviridae - genetics
Papillomavirus Infections
Papillomaviruses
Patients
PIK3AP1
Salivary gland
Salivary gland tumors
SIRT1
SIRT1 protein
Trans-Activators - genetics
Transcription Factors - genetics
Transcriptomes
Tumors
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Summary:Mucoepidermoid Carcinomas (MEC) represent the most common malignancies of salivary glands. Approximately 50% of all MEC cases are known to harbor 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 , , , and 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.
ISSN:1999-4915
1999-4915
DOI:10.3390/v14112353