Abstract
AbstractXeroderma Pigmentosum variant (XP-V) is an autosomal recessive disease with an increased risk to develop cutaneous neoplasms in sunlight exposed regions. These cells are deficient in the translesion synthesis DNA polymerase eta. Eleven skin tumors from a genetic cluster of XP-V patients had their exome sequenced. Mutational signatures identified for most tumors were related to ultraviolet exposure, such as C>T transitions targeted to pyrimidine dimers. However, four samples carry different mutational signatures, with C>A mutations associated with tobacco usage. Basal cell carcinomas showed a distinct C>A mutation spectra reflecting a novel mutational signature. Higher levels for retroposon insertions were detected in the XP-V tumors, compared to non-XP skin tumors. The results reveal other possible causes for XP-V tumors and the involvement of polymerase eta in suppressing retrotransposition. The expected high mutation burden, found in most of these tumors, renders these XP patients good candidates for immunotherapy with checkpoint blockers.
Publisher
Cold Spring Harbor Laboratory
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献