A comprehensive landscape of BRCA1 versus BRCA2 associated molecular alterations and survival outcome across 35 cancer types
| Autor: | Mohamed E. Salem, Arielle L Heeke, Sarah Sammons, Emil Lou, John L. Marshall, W. Michael Korn, Joanne Xiu, Alberto Puccini, Philip A. Philip, Andreas Seeber, Wafik S. El-Deiry, Heinz-Josef Lenz, Richard M. Goldberg, Anthony F. Shields, Thomas J. Herzog, Stephen V. Liu |
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| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Journal of Clinical Oncology. 39:3120-3120 |
| ISSN: | 1527-7755 0732-183X |
| Popis: | 3120 Background: Poly (ADP-ribose) polymerase inhibitors (PARPi) are effective therapies for some patients with both germline and somatic BRCA1/2 mutations (MTs) or with homologous recombination repair deficiency (HRD). We aimed to characterize molecular differences between BRCA1 and BRCA2 MTs and their prognostic and/or predictive impact on PARPi outcomes in various cancer subtypes using real world data (RWD). Methods: Tumor samples obtained from patients with 35 types of cancer were analyzed by whole exome sequencing (WES, Novaseq) at Caris Life Sciences (Phoenix, AZ). High genomic loss of heterozygosity (gLOH-H) was defined as LOH-H in ≥16% of tested loci. MSI/MMR was tested by fragment analysis, IHC, and WES. Overall survival (OS) extracted from insurance claims was calculated from start of treatment or tissue collection until last contact or death using Kaplan-Meier curves. P-values adjusted for multiple comparisons (q-value of < 0.05 was considered to be significant). Results: In total, 17,640 tumors were included, of which 776 (4.3%) had tumor-based BRCA1/2 MTs. BRCA1/2 MTs were most commonly seen in ovarian (N = 221/2187, 10.1%), breast (138/2506, 5.5%), prostate (61/1131, 5.4%), pancreatic (48/1430, 3.4%), and non-small cell lung (100/4046, 2.5%) cancers. BRCA2 MTs were more frequent than BRCA1 except in ovarian cancers. BRCA1 MTs were more common in younger pts (median age, 61 vs 65 years, p |
| Databáze: | OpenAIRE |
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