Association of germline variants in the APOBEC3 region with cancer risk and enrichment with APOBEC-signature mutations in tumors
| Autor: | Taro Shuin, Debra T. Silverman, Bin Zhu, Olusegun O. Onabajo, Candace D. Middlebrooks, Stephen J. Chanock, Montserrat Garcia-Closas, Stella Koutros, Núria Malats, Michiaki Kubo, A. Rouf Banday, Nathaniel Rothman, Jonine D. Figueroa, Krizia Ivana Udquim, Ashley Paquin, Manolis Kogevinas, Neal D. Freedman, Konichi Matsuda, Ludmila Prokunina-Olsson |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine APOBEC DNA Single-Stranded Breast Neoplasms Environment Biology Polymorphism Single Nucleotide Risk Assessment Germline Minor Histocompatibility Antigens 03 medical and health sciences Germline mutation Breast cancer Cell Line Tumor Cytidine Deaminase Genetics medicine Humans Protein Isoforms Neoplasm SNP Genetic Predisposition to Disease Germ-Line Mutation Bladder cancer Chromosome Mapping Proteins DNA Neoplasm medicine.disease Survival Analysis Gene expression profiling 030104 developmental biology Urinary Bladder Neoplasms Mutagenesis Mutation Female |
| Zdroj: | Middlebrooks, C D, Banday, A R, Matsuda, K, Udquim, K-I, Onabajo, O O, Paquin, A, Figueroa, J D, Zhu, B, Koutros, S, Kubo, M, Shuin, T, Freedman, N D, Kogevinas, M, Malats, N, Chanock, S J, Garcia-Closas, M, Silverman, D T, Rothman, N & Prokunina-Olsson, L 2016, ' Association of germline variants in the APOBEC3 region with cancer risk and enrichment with APOBEC-signature mutations in tumors ', Nature Genetics, vol. 48, no. 11, pp. 1330–1338 . https://doi.org/10.1038/ng.3670 |
| Popis: | High rates of APOBEC-signature mutations are found in many tumors, but factors affecting this mutation pattern are not well understood. Here we explored the contribution of two common germline variants in the APOBEC3 region. SNP rs1014971 was associated with bladder cancer risk, increased APOBEC3B expression, and enrichment with APOBEC-signature mutations in bladder tumors. In contrast, a 30-kb deletion that eliminates APOBEC3B and creates an APOBEC3A–APOBEC3B chimera was not important in bladder cancer, whereas it was associated with breast cancer risk and enrichment with APOBEC-signature mutations in breast tumors. In vitro, APOBEC3B expression was predominantly induced by treatment with a DNA-damaging drug in bladder cancer cell lines, and APOBEC3A expression was induced as part of the antiviral interferon-stimulated response in breast cancer cell lines. These findings suggest a tissue-specific role of environmental oncogenic triggers, particularly in individuals with germline APOBEC3 risk variants. |
| Databáze: | OpenAIRE |
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