| Autor: |
Korenjak M, Temiz NA, Keita S, Chavanel B, Renard C, Sirand C, Cahais V, Mayel T, Vevang KR, Jacobs FC, Guo J, Smith WE, Oram MK, Tăbăran FA, Ahlat O, Cornax I, O'Sullivan MG, Das S, Nandi SP, Cheng Y, Alexandrov LB, Balbo S, Hecht SS, Senkin S, Virard F, Peterson LA, Zavadil J |
| Jazyk: |
angličtina |
| Zdroj: |
BioRxiv : the preprint server for biology [bioRxiv] 2024 Jun 28. Date of Electronic Publication: 2024 Jun 28. |
| DOI: |
10.1101/2024.06.28.600253 |
| Abstrakt: |
Tobacco usage is linked to multiple cancer types and accounts for a quarter of all cancer-related deaths. Tobacco smoke contains various carcinogenic compounds, including polycyclic aromatic hydrocarbons (PAH), though the mutagenic potential of many tobacco-related chemicals remains largely unexplored. In particular, the highly carcinogenic tobacco-specific nitrosamines NNN and NNK form pre-mutagenic pyridyloxobutyl (POB) DNA adducts. In the study presented here, we identified genome-scale POB-induced mutational signatures in cell lines and rat tumors, while also investigating their role in human cancer. These signatures are characterized by T>N and C>T mutations forming from specific POB adducts damaging dT and dC residues. Analysis of 2,780 cancer genomes uncovered POB signatures in ∼180 tumors; from cancer types distinct from the ones linked to smoking-related signatures SBS4 and SBS92. This suggests that, unlike PAH compounds, the POB pathway may contribute uniquely to the mutational landscapes of certain hematological malignancies and cancers of the kidney, breast, prostate and pancreas. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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