Molecular characterization and clinical interpretation of BRCA1/BRCA2 variants in families from Murcia (south-eastern Spain) with hereditary breast and ovarian cancer: clinical–pathological features in BRCA carriers and non-carriers

Abstract

This is the first study performed in Murcia (south-eastern Spain) in which 592 families with hereditary breast and ovarian cancer were identified thanks to Genetic Counselling Units from this area over 6 years. Diagnostic performance was 18.1% and 194 different genetic variants were obtained. Variants with uncertain significance accounted for only 5.6% of the total number of reports, so our population has been well characterised. In BRCA1 gene, two novel variants were found (c.1859delT and c.3205C > T) and the most frequently detected mutations were c.68_69delAG, c.212 + 1G > A, c.5123C > A, c.211A > G and c.1918C > T, which together represented 56.67% of total pathogenic mutations. In BRCA2 gene, four recurrent variants were described (deletion of entire exon 2, c.9117G > A, c.3264dupT and c.3455T > G) representing 43.5% of the mutations in this gene. Mutation c.68_69delAG and deletion of entire exon 2 in BRCA1 and BRCA2 genes respectively were the most prevalent variants in our population. Regarding the genotype-phenotype relation, mutation c.212 + 1G > A appeared in an important percentage of breast and ovarian cancer cases, c.5123C > A in bilateral breast cancer and c.9117G > A in bilateral breast cancer and ovarian cancer. With respect to clinical-pathological characteristic, BRCA1/BRCA2 mutation carriers showed earlier onset age of breast tumour and higher risk of developing contra lateral breast cancer than non-informative cases. Moreover, association between either molecular subtype triple negative breast cancer or ovarian cancer and BRCA1 carriers was obtained.

Genetic and clinical characterization of BRCA-associated hereditary breast and ovarian cancer in Navarra (Spain)

“…Mutations in BRCA1 and BRCA2 genes were identified in 16% of families (26% of individuals) included in the high-risk HBOC sample. This rate is comparable with other studies [14, 18, 19] and similarly shows a decreasing trend over time, moving from 30% in 2000–2005, to 17% during (2006–2010) and 14% from 2011 to 2016. This is, most likely, due to the referral of the most severely affected families in the first years of cancer genetic services, and the use of less strict inclusion criteria in the later period, given the decrease in cost of the molecular analysis.…”

“…Nineteen per cent (10/52) of pathogenic variants were recurrent and were responsible of 50% of HBOC families (Additional files 2 and 3: Tables S1 and S2). Many common mutations in Navarra are also frequent in other Spanish populations [14–18]. More so, many of the recurrent mutations in Navarra coincide with the most frequent BRCA1/2 variants in Spain, as published in a recent international study [30].…”

Screening of BRCA1/2 genes mutations and copy number variations in patients with high risk for hereditary breast and ovarian cancer syndrome (HBOC)

“…It is also known as 187delAG, this variant is one of three main pathogenic founder variants in the Ashkenazi Jewish population [ 47 ]. In Morocco, this variant has been reported by Zoure et al [ 48 ] and Jouali et al [ 38 ] and globally, it has been found in different populations [ 49 – 51 ].…”

Association Between BRCA Status and Triple-Negative Breast Cancer: A Meta-Analysis

“…Next, 26 publications were further excluded for insufficient data ( n = 15), feline mammary focus ( n = 2), and non-original research ( n = 9) after carefully examining the full texts of the remaining 42 publications. Finally, 16 eligible publications were included in the study of meta-analysis (Haffty et al, 2006 ; Atchley et al, 2008 ; Kwong et al, 2009 ; Arun et al, 2011 ; Comen et al, 2011 ; Gonzalez-Angulo et al, 2011 ; Xu et al, 2012 ; Noh et al, 2013 ; Li et al, 2014 ; Yu et al, 2014 ; Zugazagoitia et al, 2014 ; Aleskandarany et al, 2015 ; Gabaldó Barrios et al, 2017 ; Ghouadni et al, 2017 ; Ha et al, 2017 ; Krammer et al, 2017 ). The screening method and results of the relevant studies are shown in Figure 1 and the main characteristics of participated patients are summarized in Table 1 .…”