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APOBEC Mutagenesis Is Concordant between Tumor and Viral Genomes in HPV-Positive Head and Neck Squamous Cell Carcinoma
by
Bass, Sara
, Langenbucher, Adam
, Ferris, Robert L.
, Lawrence, Michael S.
, Yeager, Meredith
, Boland, Joseph F.
, Mirabello, Lisa
, Pinheiro, Maisa
, Steinberg, Mia
, Lewis, James S.
, Faden, Daniel L.
, Lin, Maoxuan
, Cullen, Michael
, Kuhs, Krystle A. Lang
in
Adult
/ Aged
/ alleles
/ APOBEC
/ APOBEC Deaminases - genetics
/ APOBEC Deaminases - metabolism
/ Cancer
/ Editing
/ Female
/ Genes
/ Genome, Viral
/ Genomes
/ Head & neck cancer
/ head and neck squamous cell carcinoma
/ HPV
/ Human papillomavirus
/ Human papillomavirus 16 - genetics
/ Human papillomavirus 16 - physiology
/ Humanpapilloma virus
/ Humans
/ Male
/ Middle Aged
/ Mutagenesis
/ mutagens
/ Mutation
/ Mutation rates
/ oropharyngeal cancer
/ oropharyngeal squamous cell carcinoma
/ Papillomaviridae
/ Papillomavirus Infections - enzymology
/ Papillomavirus Infections - genetics
/ Papillomavirus Infections - virology
/ RNA
/ RNA editing
/ Squamous cell carcinoma
/ Squamous Cell Carcinoma of Head and Neck - enzymology
/ Squamous Cell Carcinoma of Head and Neck - genetics
/ Squamous Cell Carcinoma of Head and Neck - virology
/ Throat cancer
/ transcriptome
/ Transcriptomes
/ viral genome
/ viruses
2021
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APOBEC Mutagenesis Is Concordant between Tumor and Viral Genomes in HPV-Positive Head and Neck Squamous Cell Carcinoma
by
Bass, Sara
, Langenbucher, Adam
, Ferris, Robert L.
, Lawrence, Michael S.
, Yeager, Meredith
, Boland, Joseph F.
, Mirabello, Lisa
, Pinheiro, Maisa
, Steinberg, Mia
, Lewis, James S.
, Faden, Daniel L.
, Lin, Maoxuan
, Cullen, Michael
, Kuhs, Krystle A. Lang
in
Adult
/ Aged
/ alleles
/ APOBEC
/ APOBEC Deaminases - genetics
/ APOBEC Deaminases - metabolism
/ Cancer
/ Editing
/ Female
/ Genes
/ Genome, Viral
/ Genomes
/ Head & neck cancer
/ head and neck squamous cell carcinoma
/ HPV
/ Human papillomavirus
/ Human papillomavirus 16 - genetics
/ Human papillomavirus 16 - physiology
/ Humanpapilloma virus
/ Humans
/ Male
/ Middle Aged
/ Mutagenesis
/ mutagens
/ Mutation
/ Mutation rates
/ oropharyngeal cancer
/ oropharyngeal squamous cell carcinoma
/ Papillomaviridae
/ Papillomavirus Infections - enzymology
/ Papillomavirus Infections - genetics
/ Papillomavirus Infections - virology
/ RNA
/ RNA editing
/ Squamous cell carcinoma
/ Squamous Cell Carcinoma of Head and Neck - enzymology
/ Squamous Cell Carcinoma of Head and Neck - genetics
/ Squamous Cell Carcinoma of Head and Neck - virology
/ Throat cancer
/ transcriptome
/ Transcriptomes
/ viral genome
/ viruses
2021
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APOBEC Mutagenesis Is Concordant between Tumor and Viral Genomes in HPV-Positive Head and Neck Squamous Cell Carcinoma
by
Bass, Sara
, Langenbucher, Adam
, Ferris, Robert L.
, Lawrence, Michael S.
, Yeager, Meredith
, Boland, Joseph F.
, Mirabello, Lisa
, Pinheiro, Maisa
, Steinberg, Mia
, Lewis, James S.
, Faden, Daniel L.
, Lin, Maoxuan
, Cullen, Michael
, Kuhs, Krystle A. Lang
in
Adult
/ Aged
/ alleles
/ APOBEC
/ APOBEC Deaminases - genetics
/ APOBEC Deaminases - metabolism
/ Cancer
/ Editing
/ Female
/ Genes
/ Genome, Viral
/ Genomes
/ Head & neck cancer
/ head and neck squamous cell carcinoma
/ HPV
/ Human papillomavirus
/ Human papillomavirus 16 - genetics
/ Human papillomavirus 16 - physiology
/ Humanpapilloma virus
/ Humans
/ Male
/ Middle Aged
/ Mutagenesis
/ mutagens
/ Mutation
/ Mutation rates
/ oropharyngeal cancer
/ oropharyngeal squamous cell carcinoma
/ Papillomaviridae
/ Papillomavirus Infections - enzymology
/ Papillomavirus Infections - genetics
/ Papillomavirus Infections - virology
/ RNA
/ RNA editing
/ Squamous cell carcinoma
/ Squamous Cell Carcinoma of Head and Neck - enzymology
/ Squamous Cell Carcinoma of Head and Neck - genetics
/ Squamous Cell Carcinoma of Head and Neck - virology
/ Throat cancer
/ transcriptome
/ Transcriptomes
/ viral genome
/ viruses
2021
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APOBEC Mutagenesis Is Concordant between Tumor and Viral Genomes in HPV-Positive Head and Neck Squamous Cell Carcinoma
Journal Article
APOBEC Mutagenesis Is Concordant between Tumor and Viral Genomes in HPV-Positive Head and Neck Squamous Cell Carcinoma
2021
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Overview
APOBEC is a mutagenic source in human papillomavirus (HPV)-mediated malignancies, including HPV+ oropharyngeal squamous cell carcinoma (HPV + OPSCC), and in HPV genomes. It is unknown why APOBEC mutations predominate in HPV + OPSCC, or if the APOBEC-induced mutations observed in both human cancers and HPV genomes are directly linked. We performed sequencing of host somatic exomes, transcriptomes, and HPV16 genomes from 79 HPV + OPSCC samples, quantifying APOBEC mutational burden and activity in both host and virus. APOBEC was the dominant mutational signature in somatic exomes. In viral genomes, there was a mean of five (range 0–29) mutations per genome. The mean of APOBEC mutations in viral genomes was one (range 0–5). Viral APOBEC mutations, compared to non-APOBEC mutations, were more likely to be low-variant allele fraction mutations, suggesting that APOBEC mutagenesis actively occurrs in viral genomes during infection. HPV16 APOBEC-induced mutation patterns in OPSCC were similar to those previously observed in cervical samples. Paired host and viral analyses revealed that APOBEC-enriched tumor samples had higher viral APOBEC mutation rates (p = 0.028), and APOBEC-associated RNA editing (p = 0.008), supporting the concept that APOBEC mutagenesis in host and viral genomes is directly linked and occurrs during infection. Using paired sequencing of host somatic exomes, transcriptomes, and viral genomes, we demonstrated for the first-time definitive evidence of concordance between tumor and viral APOBEC mutagenesis. This finding provides a missing link connecting APOBEC mutagenesis in host and virus and supports a common mechanism driving APOBEC dysregulation.
Publisher
MDPI AG,MDPI
Subject
/ Aged
/ alleles
/ APOBEC
/ APOBEC Deaminases - genetics
/ APOBEC Deaminases - metabolism
/ Cancer
/ Editing
/ Female
/ Genes
/ Genomes
/ head and neck squamous cell carcinoma
/ HPV
/ Human papillomavirus 16 - genetics
/ Human papillomavirus 16 - physiology
/ Humans
/ Male
/ mutagens
/ Mutation
/ oropharyngeal squamous cell carcinoma
/ Papillomavirus Infections - enzymology
/ Papillomavirus Infections - genetics
/ Papillomavirus Infections - virology
/ RNA
/ Squamous Cell Carcinoma of Head and Neck - enzymology
/ Squamous Cell Carcinoma of Head and Neck - genetics
/ Squamous Cell Carcinoma of Head and Neck - virology
/ viruses
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