Genome-wide somatic mutation analysis of sinonasal adenocarcinoma with and without wood dust exposure.

Autor: Sipilä LJ; Department of Medical and Clinical Genetics, University of Helsinki, Biomedicum Helsinki, Haartmaninkatu 8), PO Box 63, Helsinki, FI-00014, Finland.; Applied Tumor Genomics, Research Programs Unit, University of Helsinki, Biomedicum Helsinki, Haartmaninkatu 8), PO Box 63, Helsinki, FI-00014, Finland.; Finnish Cancer Registry, Unioninkatu 22, Helsinki, 00130, Finland., Katainen R; Department of Medical and Clinical Genetics, University of Helsinki, Biomedicum Helsinki, Haartmaninkatu 8), PO Box 63, Helsinki, FI-00014, Finland.; Applied Tumor Genomics, Research Programs Unit, University of Helsinki, Biomedicum Helsinki, Haartmaninkatu 8), PO Box 63, Helsinki, FI-00014, Finland.; Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland., Aavikko M; Department of Medical and Clinical Genetics, University of Helsinki, Biomedicum Helsinki, Haartmaninkatu 8), PO Box 63, Helsinki, FI-00014, Finland.; Applied Tumor Genomics, Research Programs Unit, University of Helsinki, Biomedicum Helsinki, Haartmaninkatu 8), PO Box 63, Helsinki, FI-00014, Finland.; Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland., Ravantti J; Department of Medical and Clinical Genetics, University of Helsinki, Biomedicum Helsinki, Haartmaninkatu 8), PO Box 63, Helsinki, FI-00014, Finland.; Applied Tumor Genomics, Research Programs Unit, University of Helsinki, Biomedicum Helsinki, Haartmaninkatu 8), PO Box 63, Helsinki, FI-00014, Finland.; Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, Helsinki, FI-00014, Finland., Donner I; Organismal and Evolutionary Biology Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, Viikinkaari 9, Helsinki, 00014, Finland., Lehtonen R; Department of Medical and Clinical Genetics, University of Helsinki, Biomedicum Helsinki, Haartmaninkatu 8), PO Box 63, Helsinki, FI-00014, Finland.; Applied Tumor Genomics, Research Programs Unit, University of Helsinki, Biomedicum Helsinki, Haartmaninkatu 8), PO Box 63, Helsinki, FI-00014, Finland., Leivo I; Institute of Biomedicine, Pathology, University of Turku, Kiinamyllynkatu 10, Turku, D 5035, 20520, Finland.; Turku University Central Hospital, Turku, 20521, Finland., Wolff H; Finnish Institute of Occupational Health, PB 40, Helsinki, 00251, Finland.; Department of Pathology, University of Helsinki, PB 20, Helsinki, 00014, Finland., Holmila R; Finnish Institute of Occupational Health, PB 40, Helsinki, 00251, Finland., Husgafvel-Pursiainen K; Finnish Institute of Occupational Health, PB 40, Helsinki, 00251, Finland., Aaltonen LA; Department of Medical and Clinical Genetics, University of Helsinki, Biomedicum Helsinki, Haartmaninkatu 8), PO Box 63, Helsinki, FI-00014, Finland. lauri.aaltonen@helsinki.fi.; Applied Tumor Genomics, Research Programs Unit, University of Helsinki, Biomedicum Helsinki, Haartmaninkatu 8), PO Box 63, Helsinki, FI-00014, Finland. lauri.aaltonen@helsinki.fi.; Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, 141 83, Sweden. lauri.aaltonen@helsinki.fi.; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, 00290, Finland. lauri.aaltonen@helsinki.fi.
Jazyk: angličtina
Zdroj: Genes and environment : the official journal of the Japanese Environmental Mutagen Society [Genes Environ] 2024 May 06; Vol. 46 (1), pp. 12. Date of Electronic Publication: 2024 May 06.
DOI: 10.1186/s41021-024-00306-8
Abstrakt: Background: Sinonasal adenocarcinoma is a rare cancer, encompassing two different entities, the intestinal-type sinonasal adenocarcinoma (ITAC) and the non-intestinal-type sinonasal adenocarcinoma (non-ITAC). Occurrence of ITAC is strongly associated with exposure to hardwood dusts. In countries with predominant exposure to softwood dust the occurrence of sinonasal adenocarcinomas is lower and the relative amount of non-ITACs to ITACs is higher. The molecular mechanisms behind the tumorigenic effects of wood dust remain largely unknown.
Methods: We carried out whole-genome sequencing of formalin-fixed paraffin-embedded (FFPE) samples of sinonasal adenocarcinomas from ten wood dust-exposed and six non-exposed individuals, with partial tobacco exposure data. Sequences were analyzed for the presence of mutational signatures matching COSMIC database signatures. Driver mutations and CN variant regions were characterized.
Results: Mutation burden was higher in samples of wood dust-exposed patients (p = 0.016). Reactive oxygen species (ROS) damage-related mutational signatures were almost exclusively identified in ITAC subtype samples (p = 0.00055). Tobacco smoke mutational signatures were observed in samples of patients with tobacco exposure or missing information, but not in samples from non-exposed patients. A tetraploidy copy number (CN) signature was enriched in ITAC subtype (p = 0.042). CN variation included recurrent gains in COSMIC Cancer Gene Census genes TERT, SDHA, RAC1, ETV1, PCM1, and MYC. Pathogenic variants were observed most frequently in TP53, NF1, CHD2, BRAF, APC, and LRP1B. Driver mutations and copy number gains did not segregate by subtype.
Conclusions: Our analysis identified distinct mutational characteristics in ITAC and non-ITAC. Mutational signature analysis may eventually become useful for documentation of occupation-related cancer, while the exact mechanisms behind wood dust-driven carcinogenesis remain elusive. The presence of homologous recombination deficiency signatures implies a novel opportunity for treatment, but further studies are needed.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje