Genetic testing and first presymptomatic diagnosis in Moroccan families at high risk for breast/ovarian cancer

Laarabi, Fatima Zahra; Jaouad, Imane Cherkaoui; Ouldim, Karim; Aboussair, Nisrine; Jalil, Abdul; Gueddari, B.K. El; Benjaafar, Noureddine; Sefiani, Abdelaziz

doi:10.3892/ol.2011.248

Cited by 24 publications

(29 citation statements)

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“…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).…”

Section: Discussionmentioning

confidence: 99%

“…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%

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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: Discussionmentioning

confidence: 99%

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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“…The first study was conducted by Laarabi et al, and was interested in the study of BRCA1 / 2 mutations in 5 healthy women belonging to 3 families with an elevated risk of breast cancer. As results of this study, 3 asymptomatic women were carriers of BRCA1/2 mutations (Laarabi et al, 2011).…”

Section: Brca1/2 Mutations Found In Moroccan Patients Arementioning

confidence: 85%

“…In Morocco, it was detected in two unrelated families (Laarabi et al, 2011). The confirmation of occurrence of this mutation in the Moroccan population will be of great benefit to simplify genetic testing and may have a major impact on public health in Morocco.…”

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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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BRCA1 and BRCA2 mutations in ovarian cancer patients from China: ethnic‐related mutations in BRCA1 associated with an increased risk of ovarian cancer

Shi

Wang

Xie

et al. 2017

Intl Journal of Cancer

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NC 6 Plateforme de g enomique des cancers, Centre L eon B erard, Laboratoire de la g en etique constitutionnelle HCL-CLB, Lyon, France BRCA1/2 are cancer predisposition genes involved in hereditary breast and ovarian cancer (HBOC). Mutation carriers display an increased sensitivity to inhibitors of poly(ADP-ribose) polymerase (PARP). Despite a number of small-size hospital-based studies being previously reported, there is not yet, to our knowledge, precise data of BRCA1/2 mutations among Chinese ovarian cancer patients. We performed a multicenter cohort study including 916 unselected consecutive epithelial ovarian cancer (EOC) patients from eastern China to screen for BRCA1/2 mutations using the next-generation sequencing approach. A total of 153 EOC patients were found to carry pathogenic germline mutations in BRCA1/2, accounting for an overall mutation incidence of 16.7% with the predominance in BRCA1 (13.1%) compared with BRCA2 (3.9%). We identified 53 novel pathogenic mutations, among which the c.283_286delCTTG and the c.4573C > T of BRCA1 were both found in two unrelated patients. More importantly, the most common mutation found in this study, c.5470_5477del8 was most likely to be Chinese populationrelated without an apparent founder origin. This hot-spot mutation was presumably associated with an increased risk of ovarian cancer. Taken together, germline BRCA1/2 mutations were common in Chinese EOC patients with distinct mutational spectrum compared to Western populations. Our study contributes to the current understanding of BRCA1/2 mutation prevalence worldwide. We recommend BRCA1/2 genetic testing to all Chinese women diagnosed with EOC to identify HBOC families, to provide genetic counseling and clinical management for at-risk relatives. Mutation carriers may also benefit from PARP-targeted therapies.Ovarian cancer is the third most commonly diagnosed cancer and the first leading cause of deaths among gynecologic malignancies worldwide.

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Genetic testing and first presymptomatic diagnosis in Moroccan families at high risk for breast/ovarian cancer

Abstract: Abstract. Germline mutations in the BRCA1 and BRCA2 genes highly predispose to breast and ovarian cancers and are responsible for a substantial proportion of familial breast and ovarian cancers. No female individuals from families from Morocco affected by breast cancer with mutations of

Cited by 24 publications

References 20 publications

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

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

Breast Cancer in Morocco: A Literature Review

BRCA1 and BRCA2 mutations in ovarian cancer patients from China: ethnic‐related mutations in BRCA1 associated with an increased risk of ovarian cancer

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