Specific BRCA1 gene variations amongst young Moroccan breast cancer patients

Abstract

ABSTRACT. Germline mutations in the BRCA1 gene are known predictive markers for the development of hereditary breast cancer. Nevertheless, no comprehensive study has been performed targeting the presence and relevance of BRCA1 mutations in Moroccan breast cancer patients. We here present an analysis of BRCA1 gene regions (exon 2 and exon 11a/b) of 50 female Moroccan breast cancer patients with early disease onset (≤40 years) or familial disease backgrounds. Results showed that no mutation was present in either exon 2 or exon 11a of the BRCA1 gene in any of the 50 patients analysed. However, in exon 11b, a mutation generated by a nucleotide exchange was detected in 8% of patients, most of whom were young women (≤40). This mutation leads to substitution of the amino acid glutamine by an arginine at position 356 of the polypeptide sequence (Q356R). Although this mutation was previously characterised at a lower frequency in western populations, our study is the first to describe it in a young Moroccan population. Furthermore, another mutation was detected with a high frequency (4%) on exon 11b of the BRCA1 gene in exclusively young patients (≤40). This mutation was silent, encoding the same threonine residue at position 327 (T327T) as the wild type. The present study is the first to describe this mutation as well, particularly in a young Moroccan population. Analysis of a larger population is required in order to highlight the relevance of the Q356R and T327T mutations in young Moroccan breast cancer patients.

BRCA1 novel mutation V1736D and in silico analysis of SNP Q356R in Sudanese patients with breast cancer

“…Some studies found that this SNP is associated with patients under 40 years old, 66,67 , which agreed with our study -the youngest premenopausal patient (27 years old) was detected with this variant. Although this variant's effect remains uncertain, a previous finding to our study has described the same mutation, Q356R in Moroccan BC patients, which was the first study that described this mutation in a North African population 66 . They found that most previous studies that described this mutation were within western European populations 68 and there were no studies found in a North African population to confirm this, thus more research is needed to investigate this.…”

“…The same protein position (Q356R) with the same altered nucleotide (A/G) has also been described previously, but with a different nucleotide position c.1186 A>G 16,65,66 . Some studies found that this SNP is associated with patients under 40 years old, 66,67 , which agreed with our study -the youngest premenopausal patient (27 years old) was detected with this variant.…”

“…The same protein position (Q356R) with the same altered nucleotide (A/G) has also been described previously, but with a different nucleotide position c.1186 A>G 16,65,66 . Some studies found that this SNP is associated with patients under 40 years old, 66,67 , which agreed with our study -the youngest premenopausal patient (27 years old) was detected with this variant. Although this variant's effect remains uncertain, a previous finding to our study has described the same mutation, Q356R in Moroccan BC patients, which was the first study that described this mutation in a North African population 66 .…”

First application of next-generation sequencing in Moroccan breast/ovarian cancer families and report of a novel frameshift mutation of the BRCA1 gene

“…The mutational spectrum of BRCA1/2 in the Moroccan population is becoming partially characterised thanks to local genetic centers, who have developed oncogenetic consultations for familial forms of breast and ovarian cancers and performed molecular analyses of BRCA genes using the conventional individual exon-by-exon Sanger sequencing (10,13,14,16,17). Thus, several mutations in two particular genes have been reported in the Moroccan National Genetic Database (http:// ethnos.findbase.org/home-ma).…”

“…research.nhgri.nih.gov/bic/), the HGMD (http://www.hgmd. cf.ac.uk/ac/index.php), Clinvar (http://www.ncbi.nlm.nih.gov/ clinvar/) and previous publications (10,(13)(14)(15). Amino acid predictions were performed using the scale-invariant feature transform algorithm and PolyPhen-2 software tools (Polymorphism Phenotyping v2.2.2, developed by Dr Shamil Sunyaev, Harvard Medical School, Boston, MA, USA; http://genetics.…”