| Autor: |
Violeta Serra, Anna Hubert, Catherine Ruan, Judith Balmaña, Alba Llop-Guevara, Kara N. Maxwell, Susan M. Domchek, Anupma Nayak, Wenting Zhou, John Pluta, Dana Pueschl, Michael Feldman, Katherine L. Nathanson, Adam A. Kraya, Jennifer Shah, Bradley Wubbenhorst, Kurt D.Andrea, Jake S. Shilan |
| Rok vydání: |
2021 |
| Předmět: |
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| DOI: |
10.21203/rs.3.rs-745248/v1 |
| Popis: |
Recurrence is a major cause of death among BRCA1/2 mutation carriers with breast (BrCa) and ovarian cancers (OvCa). We performed multi-omic sequencing on 67 paired primary and recurrent BrCa and OvCa from 27 BRCA1/2 mutation carriers to identify potential recurrence-specific drivers. PARP1 amplifications were identified in recurrences (FDR q = 0.05), and PARP1 was significantly overexpressed across primary BrCa and recurrent BrCa and OvCa, independent of amplification status. RNA-seq analysis found two BRCA2 isoforms, BRCA2-201/Long and BRCA2-001/Short, predicted sensitive and insensitive to nonsense-mediated decay, respectively. BRCA2-001/Short was expressed more frequently in recurrences and associated with reduced overall survival in breast cancer (87 vs. 121 months; HR = 2.5 [1.18–5.5]). Loss of heterozygosity (LOH) status was discordant in 25% of patient’s primary and recurrent tumors, with switching between both LOH and lack of LOH found. Our study revealed multiple potential drivers of recurrent disease in BRCA1/2 mutation-associated cancer, improving our understanding of tumor evolution and suggesting potential biomarkers. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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