Abstract 4664
Background
BRCA1 and BRCA2 are the genes most frequently associated with hereditary breast and ovarian cancer (HBOC). Besides point mutations, BRCA1/2 large genomic rearrangements (LGR) have been observed, with different frequencies in specific populations. This study aims to update the frequency of BRCA1 and BRCA2 LGR in our population, as well as to characterize the gene distribution of these genetic events.
Methods
All high risk pts referred to our multidisciplinary program between 2000-2018 that consented on genetic testing were reviewed for BRCA1 and BRCA2 point pathogenic variants (several methodologies throughout the years including Conformation Sensitive Gel Electrophoresis; Conformation Sensitive Capillary Electrophoresis; Sanger Sequencing and Next Generation Sequencing) and LGR with Multiplex Ligation dependent Probe Amplification (MLPA).
Results
3763 of 3901 index pts consented on genetic testing and 473 pts had 476 different pathogenic variants (PV). In 3 cases double germline PV were observed: BRCA1 (c.68_69delAG) and CHEK2 [c.(908 + 1_909-1)_(1095 + 1_1096-1)del]; ATM (c.8264_8268delATAAG) and PALB2 (c.751C>T); BRCA2 (c.156_157insAlu) and CHEK2 (c.593-1G>T). BRCA1 PV were detected in 151 pts with 24 LGR of these (15,9%) being detected by MLPA. The most frequent BRCA1 LGR was c. (4185 + 1_4186-1)_(4357 + 1_4358-1)dup (n = 8). BRCA2 PV were detected in 260 pts with 99 LGR: 92 pts with the Portuguese founder mutation c.156_157insAlu (detected by specific PCR or MLPA) and 7 pts with other LGR (detected by MLPA). The second most frequent BRCA2 LGR was c. (8632 + 1_8633-1)_(8754 + 1_8755-1)dup (n = 5). Nine CHEK2 PV were detected with the SALSA MLPA probemix P045 BRCA2/CHEK2: c.1100delC (8 pts) and c. (908 + 1_909-1)_(1095 + 1_1096-1)del (1pt). The total percentage of BRCA1 and BRCA2 LGR in our cohort was 26%. Excluding the Portuguese founder mutation c.156_157insAlu, the prevalence of LGR was 6,5%.
Conclusions
There is a high prevalence of LGR in the Portuguese population, mostly because of the Portuguese founder mutation c.156_157insAlu. Even if excluding this event, other LRG still account for 6,5% of the BRCA1 and BRCA2 pathogenic variants. These results emphasize the importance of testing LGR in all patients with high risk HBOC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
2273 - High performance of serial tumor biopsies in first in human (FIH) phase I trials.
Presenter: Jun Sato
Session: Poster Display session 1
Resources:
Abstract
5933 - Response rates and lesion-level progression patterns of solid tumor patients in an academic phase 1 program: implications for tumor heterogeneity
Presenter: Christopher Chen
Session: Poster Display session 1
Resources:
Abstract
3569 - Clinical Benefit and Response Rate in Early Phase Clinical Trials: First Report from a Single-Institution Study
Presenter: Antonio Marra
Session: Poster Display session 1
Resources:
Abstract
4139 - Patient (pt) selection for immunotherapeutic early-phase clinical trials (ieCTs): a single Phase I Unit experience
Presenter: Matteo Simonelli
Session: Poster Display session 1
Resources:
Abstract
4451 - Improving patient selection for immuno-oncology phase 1 trials: an external validation of five prognostic scores at Claudius Regaud Institute of Toulouse, Oncopôle (IUCT-O).
Presenter: Ghassan Al Darazi
Session: Poster Display session 1
Resources:
Abstract
1696 - Demonstrating the Changing Trends in Phase 1 Clinical Trials
Presenter: Christina Guo
Session: Poster Display session 1
Resources:
Abstract
3202 - Participation of Women in phase 1 oncology clinical trials
Presenter: Laura Vidal
Session: Poster Display session 1
Resources:
Abstract
4518 - Predictors for early trial discontinuation of patients with cancer participating in phase I clinical trials
Presenter: Joeri Douma
Session: Poster Display session 1
Resources:
Abstract
4368 - Safety of Tumor Treating Fields delivery to the torso: Meta analysis from TTFields clinical trials
Presenter: Federica Grosso
Session: Poster Display session 1
Resources:
Abstract
4615 - Proteomic Profiling Identifies Molecular Basis of Adverse Event to BPM31510 Exposure: Rationale for Comprehensive Molecular Pharmacodynamics (PD) in Phase 1 Clinical Trial Design
Presenter: Vivek Subbiah
Session: Poster Display session 1
Resources:
Abstract