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
5011 - LCSCAF1 maintains cancer stem-like traits by stabilizing c-Myc protein and promotes metastasis and recurrence in lung cancer
Presenter: Tao Guo
Session: Poster Display session 1
Resources:
Abstract
4955 - XAF1 Enhances Temozolomide Induced Autophagic Cell Death through AMPK signaling pathway
Presenter: Mingoo Lee
Session: Poster Display session 1
Resources:
Abstract
5616 - The effect of cortisol on methylation patterns in breast cancer cell lines
Presenter: Haya Intabli
Session: Poster Display session 1
Resources:
Abstract
4649 - Global and sex-specific epigenome-wide association studies for the identification of the main methylated loci related to smoking in a Mediterranean population
Presenter: Judith Begona Ramirez Sabio
Session: Poster Display session 1
Resources:
Abstract
4984 - Whole transcriptomics analyses of mimicking Circulating Tumor Cells (CTCs) by single-cell RNA sequencing (scRNAseq)
Presenter: Jessica Garcia
Session: Poster Display session 1
Resources:
Abstract
5926 - Comparison of enzymatic- and bisulfite conversion to map the plasma cell-free methylome in cancer
Presenter: Nicole Lambert
Session: Poster Display session 1
Resources:
Abstract
5454 - Detection of low mutations in hepatocellular carcinoma by using circulating tumor DNA
Presenter: Esl Kim
Session: Poster Display session 1
Resources:
Abstract
4428 - Variants in the JAK1 and JAK2 genes in the risk and prognosis of patients with cutaneous melanoma
Presenter: Bruna Carvalho
Session: Poster Display session 1
Resources:
Abstract
4409 - P-Rex1 expression in breast cancer patients.
Presenter: Angela Lara Montero
Session: Poster Display session 1
Resources:
Abstract
4185 - Modulation of Risk of Cutaneous Melanoma Patients by Variants in STAT3 Gene and Functional Analysis
Presenter: Gabriela Gomez
Session: Poster Display session 1
Resources:
Abstract