Refereed journal article or data article (A1)

Oncogenic Merkel Cell Polyomavirus T Antigen Truncating Mutations are Mediated by APOBEC3 Activity in Merkel Cell Carcinoma




List of Authors: Soikkeli Anni I, Kyläniemi Minna K, Sihto Harri, Alinikula Jukka

Publisher: American Association for Cancer Research

Place: Philadelphia, PA

Publication year: 2022

Journal: Cancer Research Communications

Journal acronym: Cancer Research Communications

Volume number: 2

Issue number: 11

DOI: http://dx.doi.org/10.1158/2767-9764.CRC-22-0211

URL: https://doi.org/10.1158/2767-9764.CRC-22-0211

Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/177132064


Abstract

Merkel cell carcinoma (MCC) is an aggressive skin cancer, which is frequently caused by Merkel cell polyomavirus (MCPyV). Mutations of MCPyV tumor (T) antigens are major pathologic events of virus-positive (MCPyV+) MCCs, but their source is unclear. Activation-induced cytidine deaminase (AID)/APOBEC family cytidine deaminases contribute to antiviral immunity by mutating viral genomes and are potential carcinogenic mutators. We studied the contribution of AID/APOBEC cytidine deaminases to MCPyV large T (LT) truncation events. The MCPyV LT area in MCCs was enriched with cytosine-targeting mutations, and a strong APOBEC3 mutation signature was observed in MCC sequences. AICDA and APOBEC3 expression were detected in the Finnish MCC sample cohort, and LT expression correlated with APOBEC3H and APOBEC3G. Marginal but statistically significant somatic hypermutation targeting activity was detected in the MCPyV regulatory region. Our results suggest that APOBEC3 cytidine deaminases are a plausible cause of the LT truncating mutations in MCPyV+ MCC, while the role of AID in MCC carcinogenesis is unlikely.


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Last updated on 2022-12-12 at 08:47