Pan, Jia-Wern and Zabidi, Muhammad Mamduh Ahmad and Chong, Boon-Keat and Meng, Mei-Yee and Ng, Pei-Sze and Hasan, Siti Norhidayu and Sandey, Bethan and Bahnu, Saira and Rajadurai, Pathmanathan and Yip, Cheng-Har and Rueda, Oscar M. and Caldas, Carlos and Chin, Suet-Feung and Teo, Soo-Hwang (2021) Germline APOBEC3B deletion increases somatic hypermutation in Asian breast cancer that is associated with Her2 subtype, PIK3CA mutations and immune activation. International Journal of Cancer, 148 (10). pp. 2489-2501. ISSN 0020-7136, DOI https://doi.org/10.1002/ijc.33463.
Full text not available from this repository.Abstract
A 30-kb deletion that eliminates the coding region of APOBEC3B (A3B) is >5 times more common in women of Asian descent compared to European descent. This polymorphism creates a chimera with the APOBEC3A (A3A) coding region and A3B 3 ` UTR, and it is associated with an increased risk for breast cancer in Asian women. Here, we explored the relationship between the A3B deletion polymorphism with tumour characteristics in Asian women. Using whole exome and whole transcriptome sequencing data of 527 breast tumours, we report that germline A3B deletion polymorphism leads to expression of the A3A-B hybrid isoform and increased APOBEC-associated somatic hypermutation. Hypermutated tumours, regardless of A3B germline status, were associated with the Her2 molecular subtype and PIK3CA mutations. Compared to nonhypermutated tumours, hypermutated tumours also had higher neoantigen burden, tumour heterogeneity and immune activation. Taken together, our results suggest that the germline A3B deletion polymorphism, via the A3A-B hybrid isoform, contributes to APOBEC mutagenesis in a significant proportion of Asian breast cancers. In addition, APOBEC somatic hypermutation, regardless of A3B background, may be an important clinical biomarker for Asian breast cancers.
| Item Type: | Article |
|---|---|
| Funders: | Cancer Research UK[A16942], Newton-Ungku Omar Fund[MR/P012442/1], UK Research & Innovation (UKRI) Medical Research Council UK (MRC)[MR/P012442/1] |
| Uncontrolled Keywords: | APOBEC mutagenesis;APOBEC3A;APOBEC3B;Asian breast cancer; Somatic hypermutation |
| Subjects: | H Social Sciences > HT Communities. Classes. Races R Medicine R Medicine > R Medicine (General) |
| Divisions: | Faculty of Medicine |
| Depositing User: | Ms Zaharah Ramly |
| Date Deposited: | 30 May 2022 03:29 |
| Last Modified: | 30 May 2022 03:29 |
| URI: | http://eprints.um.edu.my/id/eprint/34553 |
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