Expression of DNA mismatch repair proteins and MSH2 polymorphisms in nonmelanoma skin cancers of organ transplant recipients

Abstract

Organ transplant recipients (OTRs) have an increased risk of skin cancer. Treatment with azathioprine, commonly used in post-transplant immunosuppressive regimens, results in incorporation of 6-thioguanine (6-TG) into DNA. Mismatch repair (MMR)-defective cells are resistant to killing by 6-TG. Azathioprine exposure confers a survival advantage on MMR-defective cells, which are hypermutable and may therefore contribute to azathioprine-related nonmelanoma skin cancer, a phenomenon we have previously demonstrated in transplant-associated sebaceous carcinomas. The MSH2 protein is an important component of DNA MMR. The -6 exon 13 T>C MSH2 polymorphism is associated with impaired MMR, drug resistance and certain cancers.

Journal details

Volume 162
Issue number 4
Pages 732-742
Publication date

Keywords

Crick labs/facilities