APOBEC-Mediated Cytosine Deamination Links PIK3CA Helical Domain Mutations to Human Papillomavirus-Driven Tumor Development
APOBEC-Mediated Cytosine Deamination Links PIK3CA Helical Domain Mutations to Human Papillomavirus-Driven Tumor Development
APOBEC3B cytosine deaminase activity has recently emerged as a significant mutagenic factor in human cancer. APOBEC activity is induced in virally infected cells, and APOBEC signature mutations occur at high frequency in cervical cancers (CESC), over 99HPV). We tested whether APOBEC-mediated mutagenesis is particularly important in HPV-associated tumors by comparing the exomes of HPV+ and HPV- head and neck squamous cell carcinomas (HNSCCs) sequenced by The Cancer Genome Atlas project. As expected, HPV- HNSCC displays a smoking-associated mutational signature, whereas our data suggest that reduced exposure to exogenous carcinogens in HPV+ HNSCC creates a selective pressure that favors emergence of tumors with APOBEC-mediated driver mutations. Finally, we provide evidence that APOBEC activity is responsible for the?generation of helical domain hot spot mutations in the PIK3CA gene across multiple cancers. Our?findings implicate APOBEC activity as a key driver?of PIK3CA mutagenesis and HPV-induced transformation.
1833-1841
Henderson, S
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Chakravarthy, A
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Su, X
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Boshoff, C
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Fenton, TR
087260ba-f6a1-405a-85df-099d05810a84
1 June 2014
Henderson, S
1f160dd8-a921-4a12-91bb-588a1890c7f3
Chakravarthy, A
736774ce-5094-45d8-a148-aaa35466297e
Su, X
b067387d-d821-4d24-a98f-8f8670a25b68
Boshoff, C
7a31a970-ff94-4ea6-b24a-dab87ae08074
Fenton, TR
087260ba-f6a1-405a-85df-099d05810a84
Henderson, S, Chakravarthy, A, Su, X, Boshoff, C and Fenton, TR
(2014)
APOBEC-Mediated Cytosine Deamination Links PIK3CA Helical Domain Mutations to Human Papillomavirus-Driven Tumor Development.
Cell Reports, 7 (6), .
(doi:10.1016/j.celrep.2014.05.012).
Abstract
APOBEC3B cytosine deaminase activity has recently emerged as a significant mutagenic factor in human cancer. APOBEC activity is induced in virally infected cells, and APOBEC signature mutations occur at high frequency in cervical cancers (CESC), over 99HPV). We tested whether APOBEC-mediated mutagenesis is particularly important in HPV-associated tumors by comparing the exomes of HPV+ and HPV- head and neck squamous cell carcinomas (HNSCCs) sequenced by The Cancer Genome Atlas project. As expected, HPV- HNSCC displays a smoking-associated mutational signature, whereas our data suggest that reduced exposure to exogenous carcinogens in HPV+ HNSCC creates a selective pressure that favors emergence of tumors with APOBEC-mediated driver mutations. Finally, we provide evidence that APOBEC activity is responsible for the?generation of helical domain hot spot mutations in the PIK3CA gene across multiple cancers. Our?findings implicate APOBEC activity as a key driver?of PIK3CA mutagenesis and HPV-induced transformation.
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Published date: 1 June 2014
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copyright 2014 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/).
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Local EPrints ID: 453906
URI: http://eprints.soton.ac.uk/id/eprint/453906
ISSN: 2211-1247
PURE UUID: 3dd8e6b6-9c7d-42b3-ac21-7f3034606593
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Date deposited: 25 Jan 2022 17:51
Last modified: 17 Mar 2024 04:11
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Author:
S Henderson
Author:
A Chakravarthy
Author:
X Su
Author:
C Boshoff
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