BRCA1 and BRCA2 germline mutations in Moroccan breast/ovarian cancer families: Novel mutations and unclassified variants

Tazzite, Amal; Jouhadi, H.; Nadifi, Sellama; Aretini, Paolo; Falaschi, Elisabetta; Collavoli, Anita; Benider, Abdellatif; Caligo, Maria A.

doi:10.1016/j.ygyno.2012.03.007

Cited by 55 publications

(75 citation statements)

References 32 publications

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“…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.…”

Section: Template Preparation By Emulsion Polymerase Chain Reaction (mentioning

confidence: 99%

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

et al. 2016

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Abstract. At present, breast cancer is the most common type of cancer in females. The majority of cases are sporadic, but 5-10% are due to an inherited predisposition to develop breast and ovarian cancers, which are transmitted as an autosomal dominant form with incomplete penetrance. The beneficial effects of clinical genetic testing, including next generation sequencing (NGS) for BRCA1/2 mutations, is major; in particular, it benefits the care of patients and the counseling of relatives that are at risk of breast cancer, in order to reduce breast cancer mortality. BRCA genetic testing was performed in 15 patients with breast cancer and a family with positivity for the heterozygous c.6428C>A mutation of the BRCA2 gene. Informed consent was obtained from all the subjects. Genomic DNAs were extracted and the NGS for genes was performed using the Ion Torrent Personal Genome Machine (PGM) with a 316 chip. The reads were aligned with the human reference HG19 genome to elucidate variants in the BRCA1 and BRCA2 genes. Mutations detected by the PGM platform were confirmed by target direct Sanger sequencing on a second patient DNA sample. In total, 4 BRCA variants were identified in 6 families by NGS. Of these, 3 mutations had been previously reported: c.2126insA of BRCA1, and c.1310_1313delAAGA and c.7235insG of BRCA2. The fourth variant, c.3453delT in BRCA1, has, to the best of our knowledge, never been previously reported. The present study is the first to apply NGS of the BRCA1 and BRCA2 genes to a Moroccan population, prompting additional investigation into local founder mutations and variant characteristics in the region. The variants with no clear clinical significance may present a diagnostic challenge when performing targeted resequencing. These results confirm that an NGS approach based on Ampliseq libraries and PGM sequencing is a highly efficient, speedy and high-throughput mutation detection method, which may be preferable in lower income countries. IntroductionAt present, breast cancer is the most common type of cancer in females (1). The majority of cases are sporadic, but 5-10% are due to an inherited predisposition to develop breast and ovarian cancers, which are transmitted as an autosomal dominant form with incomplete penetrance (2,3). Germline mutations of BRCA1 and BRCA2 genes are involved in ~10 and 3-5% of ovarian and breast cancers, respectively (4,5). According to various professional society guidelines, BRCA1 and BRCA2 hereditary breast and ovarian cancer is characterised by: Multiple family members that possess breast, ovarian or both cancers; occurring at young ages or bilaterally in the case of breast cancer, triple-negative (estrogen receptor-, progesterone receptor-and human epidermal growth factor receptor 2/neu-negative) breast cancer and male breast cancer; and an increased risk of prostate, pancreatic and endometrial cancers (6,7). BRCA1 and BRCA2 are tumor suppressor genes associated with DNA damage recognition, double-strand break repair, checkpoint control, transcription regulation ...

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Section: Template Preparation By Emulsion Polymerase Chain Reaction (mentioning

confidence: 99%

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

et al. 2016

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“…This mutation was also found in four Algerian families (Uhrhammer et al, 2008;Cherbal et al, 2010), three unrelated Tunisian families (Mahfoudh et al, 2011) and recently in a Moroccan patients (Tazzite et al, 2012;Laraqui et al, 2013) . These findings suggest the presence of a founder effect mutation in the Mediterranean population.…”

Section: C798_799delttmentioning

confidence: 56%

“…Mutation c.181T> G (300T> G), was recently found in a 38 years old Moroccan patient diagnosed with breast cancer with a family history of breast / ovarian cancer (Tazzite et al, 2012). It is described as a founder mutation in the population of Central Europe (Ramunas et al, 2010) and was also observed in an Algerian study (Cherbal et al, 2010).…”

Section: C798_799delttmentioning

confidence: 90%

“…Tazzite et al showed that 25.64% of patients carried BRCA1/2 mutations (Tazzite et al, 2012). This prevalence is higher compared to Tunisia and Algeria with respectively 19.4% and 11.4% of breast cancer patients carrying BRCA1/2 mutations (Troudi et al, 2007;Cherbal et al, 2010).…”

Section: Brca1/2 Mutations Found In Moroccan Patients Arementioning

confidence: 99%

“…Overall, 14 BRCA1/2 point mutations have been reported; 9 in BRCA1 and 5 in BRCA2 (Laarabi et al, 2011;Tazzite et al, 2012;Laraqui et al, 2013) and are summarized in Table 3.…”

Section: Brca1/2 Mutations Found In Moroccan Patients Arementioning

confidence: 99%

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Breast Cancer in Morocco: A Literature Review

Slaoui¹,

Rachid²,

Ibrahimi³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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In Morocco, breast cancer is the most prevalent cancer in women and a major public health problem. Several Moroccan studies have focused on studying this disease, but more are needed, especially at the genetic and molecular levels. It is therefore interesting to establish the genetic and molecular profile of Moroccan patients with breast cancer. In this paper, we will highlight some pertinent hypotheses that may enhance breast cancer care in Moroccan patients. This review will give a precise description of breast cancer in Morocco and propose some new markers for detection and prediction of breast cancer prognosis.

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