The DNA damage repair landscape in Black women with breast cancer
| Autor: | Aloran Mazumder, Athena Jimenez, Rachel E. Ellsworth, Stephen J. Freedland, Sophia George, Matthew N. Bainbridge, Svasti Haricharan |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Therapeutic Advances in Medical Oncology, Vol 14 (2022) |
| Druh dokumentu: | article |
| ISSN: | 1758-8359 17588359 |
| DOI: | 10.1177/17588359221075458 |
| Popis: | Background: Estrogen receptor positive (ER+) breast cancer is one of the most commonly diagnosed malignancies in women irrespective of their race or ethnicity. While Black women with ER+ breast cancer are 42% more likely to die of their disease than White women, molecular mechanisms underlying this disparate outcome are understudied. Recent studies identify DNA damage repair (DDR) genes as a new class of endocrine therapy resistance driver that contributes to poor survival among ER+ breast cancer patients. Here, we systematically analyze DDR regulation in the tumors and normal breast of Black women and its impact on survival outcome. Method: Mutation and up/downregulation of 104 DDR genes in breast tumor and normal samples from Black patients relative to White counterparts was assessed. For DDR genes that were differently regulated in the tumor samples from Black women in multiple datasets associations with survival outcome were tested. Results: Overall, Black patient tumors upregulate or downregulate RNA levels of a wide array of single strand break repair (SSBR) genes relative to their white counterparts and uniformly upregulate double strand break repair (DSBR) genes. This DSBR upregulation was also detectable in samples of normal breast tissue from Black women. Eight candidate DDR genes were reproducibly differently regulated in tumors from Black women and associated with poor survival. A unique DDR signature comprised of simultaneous upregulation of homologous recombination gene expression and downregulation of SSBR genes was enriched in Black patients. This signature associated with cell cycle dysregulation ( p |
| Databáze: | Directory of Open Access Journals |
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