Mutational signatures and increased retrotransposon insertions in xeroderma pigmentosum variant skin tumors
| العنوان: | Mutational signatures and increased retrotransposon insertions in xeroderma pigmentosum variant skin tumors |
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| المؤلفون: | Camila Corradi, Juliana B Vilar, Vanessa C Buzatto, Tiago A de Souza, Ligia P Castro, Veridiana Munford, Rodrigo De Vecchi, Pedro A F Galante, Fernanda Orpinelli, Thiago L A Miller, José L Buzzo, Mirian N Sotto, Paulo Saldiva, Jocelânio W de Oliveira, Sulamita C W Chaibub, Alain Sarasin, Carlos F M Menck |
| المصدر: | Carcinogenesis. |
| بيانات النشر: | Oxford University Press (OUP), 2023. |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Cancer Research, General Medicine |
| الوصف: | Xeroderma pigmentosum variant (XP-V) is an autosomal recessive disease with an increased risk of developing cutaneous neoplasms in sunlight-exposed regions. These cells are deficient in the translesion synthesis (TLS) DNA polymerase eta, responsible for bypassing different types of DNA lesions. From the exome sequencing of 11 skin tumors of a genetic XP-V patients’ cluster, classical mutational signatures related to sunlight exposure, such as C>T transitions targeted to pyrimidine dimers, were identified. However, basal cell carcinomas also showed distinct C>A mutation spectra reflecting a mutational signature possibly related to sunlight-induced oxidative stress. Moreover, four samples carry different mutational signatures, with C>A mutations associated with tobacco chewing or smoking usage. Thus, XP-V patients should be warned of the risk of these habits. Surprisingly, higher levels of retrotransposon somatic insertions were also detected when the tumors were compared with non-XP skin tumors, revealing other possible causes for XP-V tumors and novel functions for the TLS polymerase eta in suppressing retrotransposition. Finally, the expected high mutation burden found in most of these tumors renders these XP patients good candidates for checkpoint blockade immunotherapy. |
| تدمد: | 1460-2180 0143-3334 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::8084142f94cb486a30e9ef839f389caf https://doi.org/10.1093/carcin/bgad030 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi...........8084142f94cb486a30e9ef839f389caf |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14602180 01433334 |
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