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APOBEC-Mediated Cytosine Deamination Links PIK3CA Helical Domain Mutations to Human Papillomavirus-Driven Tumor Development
Open accessAbstract
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 99% of which are caused by human papillomavirus (HPV). 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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Cites
Comprehensive molecular portraits of human breast tumours
The Cancer Genome Atlas Network (2012) · Nature · doi:10.1038/nature11412 · Cited by 12,129
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Mutational heterogeneity in cancer and the search for new cancer-associated genes
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Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts
Mangeat, B., Turelli, P., Caron, G., Friedli, M., Perrin, L., & Trono, D. (2003) · Nature · doi:10.1038/nature01709 · Cited by 1,486
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Integrated genomic and molecular characterization of cervical cancer
The Cancer Genome Atlas Research Network (2017) · Nature · doi:10.1038/nature21386 · Cited by 1,479
Whole-exome sequencing of pancreatic cancer defines genetic diversity and therapeutic targets
Witkiewicz, A. K., McMillan, E. A., Balaji, U., Baek, G., Lin, W.-C., Mansour, J., Mollaee, M., Wagner, K.-U., Koduru, P., Yopp, A., et al. (2015) · Nature Communications · doi:10.1038/ncomms7744 · Cited by 1,115
Biological and therapeutic impact of intratumor heterogeneity in cancer evolution
McGranahan, N., & Swanton, C. (2015) · Cancer Cell · doi:10.1016/j.ccell.2014.12.001 · Cited by 1,077
Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy
Skoulidis, F., & Heymach, J. V. (2019) · Nature Reviews Cancer · doi:10.1038/s41568-019-0179-8 · Cited by 1,019
Genomic correlates of response to immune checkpoint blockade in microsatellite-stable solid tumors
Miao, D., Margolis, C. A., Vokes, N. I., Liu, D., Taylor-Weiner, A., Wankowicz, S. M., Adeegbe, D., Keliher, D., Schilling, B., Tracy, A., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0200-2 · Cited by 620
Metadata
- Authors
- Henderson, S., Chakravarthy, A., Su, X., Boshoff, C., & Fenton, T. R.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2014-06
- Volume
- 7
- Issue
- 6
- Pages
- 1833-1841
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2008811015
- Cited by
- 345
- References
- 4
- FWCI
- 10.40
- Type
- journal article
- Language
- en
- Open access
- gold
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- CoChat. (2026). Citation check: APOBEC-Mediated Cytosine Deamination Links PIK3CA Helical Domain Mutations to Human Papillomavirus-Driven Tumor Development. https://app.cochat.ai/papers/10.1016/j.celrep.2014.05.012
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- Henderson, S., Chakravarthy, A., Su, X., Boshoff, C., & Fenton, T. R. (2014). APOBEC-Mediated Cytosine Deamination Links PIK3CA Helical Domain Mutations to Human Papillomavirus-Driven Tumor Development. Cell Reports. https://doi.org/10.1016/j.celrep.2014.05.012
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
