Vertaisarvioitu alkuperäisartikkeli tai data-artikkeli tieteellisessä aikakauslehdessä (A1)

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




Julkaisun tekijätSoikkeli Anni I, Kyläniemi Minna K, Sihto Harri, Alinikula Jukka

KustantajaAmerican Association for Cancer Research

PaikkaPhiladelphia, PA

Julkaisuvuosi2022

JournalCancer Research Communications

Lehden akronyymiCancer Research Communications

Volyymi2

Julkaisunumero11

Aloitussivu1344

Lopetussivun numero1354

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

Verkko-osoitehttps://doi.org/10.1158/2767-9764.CRC-22-0211

Rinnakkaistallenteen osoitehttps://research.utu.fi/converis/portal/detail/Publication/177132064


Tiivistelmä

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 2023-06-04 at 09:18