Mutational signatures and increased retrotransposon insertions in xeroderma pigmentosum variant skin tumors.

Autor:	Corradi C; Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil., Vilar JB; Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil., Buzatto VC; Molecular Oncology Center, Bioinformatics Laboratory, Hospital Sírio-Libanês, São Paulo, SP 01308-060, Brazil., de Souza TA; Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil.; Tau GC Bioinformatics, Cotia, SP 06711-020, Brazil., Castro LP; Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil., Munford V; Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil., De Vecchi R; L'Oréal Research & Innovation, Rio de Janeiro, RJ 21044-020, Brazil., Galante PAF; Molecular Oncology Center, Bioinformatics Laboratory, Hospital Sírio-Libanês, São Paulo, SP 01308-060, Brazil., Orpinelli F; Molecular Oncology Center, Bioinformatics Laboratory, Hospital Sírio-Libanês, São Paulo, SP 01308-060, Brazil., Miller TLA; Molecular Oncology Center, Bioinformatics Laboratory, Hospital Sírio-Libanês, São Paulo, SP 01308-060, Brazil.; Department of Biochemistry, Institute of Chemistry, University of Sao Paulo, Sao Paulo, SP 05508-000, Brazil., Buzzo JL; Molecular Oncology Center, Bioinformatics Laboratory, Hospital Sírio-Libanês, São Paulo, SP 01308-060, Brazil., Sotto MN; Medical School, University of Sao Paulo, Sao Paulo, SP 01246-903, Brazil., Saldiva P; Medical School, University of Sao Paulo, Sao Paulo, SP 01246-903, Brazil., de Oliveira JW; Institute of Mathematics and Statistics, University of São Paulo, São Paulo, SP 05508-090, Brazil., Chaibub SCW; Goiânia General Hospital, Goiânia, GO 74110-010, Brazil., Sarasin A; Laboratory of Genetic Instability and Oncogenesis, UMR8200 CNRS, Gustave Roussy, Université Paris-Sud, Villejuif, France., Menck CFM; Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil.
Jazyk:	angličtina
Zdroj:	Carcinogenesis [Carcinogenesis] 2023 Aug 18; Vol. 44 (6), pp. 511-524.
DOI:	10.1093/carcin/bgad030
Abstrakt:	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. (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
Databáze:	MEDLINE
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