Contribution of BRCA1 and BRCA2 germline mutations to early onset breast cancer: a series from north of Morocco

Bakkach, Joaira; Mansouri, Mohamed; Derkaoui, Touria; Loudiyi, Ali; Fahime, Elmostafa El; Barakat, Amina; Nourouti, Naima Ghailani; Villarreal, Jaime Martínez de; Bringas, Carlos; Mechita, Mohcine Bennani

doi:10.1186/s12885-020-07352-9

Cited by 14 publications

(7 citation statements)

References 55 publications

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“…On the other hand, it is interesting to note that the BRCA mutation rate in young patients diagnosed with BC (age ≤ 30 years) was higher (22.2%) compared to older patients (13.7% (31–40), 8.3% (41–50), and 11.5% (≥ 51 years). The recent study of Bakkach et al, reported that the frequency of mutations among young patients (≤ 40 years) with family history of BC was 16.7% (5 out of 33 patients) suggesting that the young age for BC diagnosis seems to be strongly predictive of BRCA mutation status in Moroccan patients [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Novel and recurrent BRCA1/BRCA2 germline mutations in patients with breast/ovarian cancer: a series from the south of Tunisia

et al. 2021

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Background The incidence of breast cancer (BC) and/or ovarian cancer (OC) is increasing in Tunisia especially in young women and mostly those with family history. However, the spectrum of BRCA mutations remains little explored in Tunisian patients in particular in the southern region. Methods We sequenced the entire coding regions of BRCA1and BRCA2 genes using next generation sequencing (NGS) in 134 selected patients with BC and/or OC. Results Among the 134 patients, 19 (14.17%) carried pathogenic mutations (10 are BRCA1 mutation carriers and 9 are BRCA2 mutation carriers) that are mainly frameshift index (76.9%). Interestingly, 5 out of the 13 variants (38.46%) were found at least twice in unrelated patients, as the c.1310-1313 delAAGA in BRCA2 and the c.5030_5033 delCTAA that has been identified in 4/98 BC patients and in 3/15 OC patients from unrelated families with strong history of cancer. Besides recurrent mutations, 6 variant (4 in BRCA1 and 2 in BRCA2) were not reported previously. Furthermore, 3 unrelated patients carried the VUS c.9976A > T, (K3326*) in BRCA2 exon 27. BRCA carriers correlated significantly with tumor site (p = 0.029) and TNBC cases (p = 0.008). In the groups of patients aged between 31 and 40, and 41–50 years, BRCA1 mutations occurred more frequently in patients with OC than those with BC, and conversely BRCA2 carriers are mostly affected with BC (p = 0.001, and p = 0.044 respectively). Conclusions The overall frequency of the BRCA germline mutations was 14.17% in patients with high risk of breast/ovarian cancer. We identified recurrent mutations as the c.1310_1313 delAAGA in BRCA2 gene and the c.5030_5033 delCTAA in BRCA1 gene that were found in 4% and 20% of familial BC and OC respectively. Our data will contribute in the implementation of genetic counseling and testing for families with high-risk of BC and/or OC.

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Section: Discussionmentioning

confidence: 99%

Novel and recurrent BRCA1/BRCA2 germline mutations in patients with breast/ovarian cancer: a series from the south of Tunisia

et al. 2021

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“…The search of the databases yielded 25 relevant references which are closely related to de ning the inclusion criteria and was included in this review. The retrieved articles describe studies conducted in Morocco (n = 11) [9][10][11][12][13][14][15][16][17][18][19], Algeria (n = 5) [20][21][22][23][24], and Tunisia (n = 9) [25][26][27][28][29][30][31][32][33]. Overall, 15 studies investigated both BRCA1 and BRCA2 genes [9, 10, 13, 16-19, 21-23, 25, 28, 30-33], four studies examined the entire coding regions of the BRCA1 gene [11,20,26,27], and six studies in which the analysis was restricted to a few BRCA1 and/or BRCA2 exons [12,14,15,24,29].…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, the BRCA1 c.798_799detTT was identi ed in 14% (18/129) of BRCA1 carriers in North African populations. It was initially thought to be speci c to Algeria (5/26, 19.23%) [20,21], but later found to be prevalent in Tunisia (4/54, 7.4%) [26,27,30] and Morocco (9/49, 18.4%) [10,11,13,[16][17][18]. Haplotype analysis of some families carrying this PVs revealed the presence of a common allele [20].…”

Section: Discussionmentioning

confidence: 99%

Prevalence of specific and recurrent/founder pathogenic variants in BRCA genes in breast and ovarian cancer in North Africa

ElBiad¹,

Laraqui²,

Boukhrissi³

et al. 2021

Preprint

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Background Elucidation of specific and recurrent/founder pathogenic variants (PVs) in BRCA (BRCA1 and BRCA2) genes can have an impact on breast cancer (BC) and/or ovarian cancer (OC) risk, making genetic testing affordable and accessible. Methods To establish the knowledge about BRCA PVs and to determine the prevalence of the specific and recurrent/founder variants in BRCA genes in BC and/or OC women in North Africa, a systematic review was conducted in Morocco, Algeria, and Tunisia. Results Search of the databases yielded 25 relevant references, including eleven studies in Morocco, five in Algeria, and nine in Tunisia. Overall, 15 studies investigated both BRCA1 and BRCA2 genes, four studies examined the entire coding region of the BRCA1 gene, and six studies in which the analysis was limited to a few BRCA1 and/or BRCA2 exons. Overall, 76 PVs (44 in BRCA1 and 32 in BRCA2) were identified in 196 BC and/or OC patients (129 BRCA1 and 67 BRCA2 carriers). Eighteen of the 76 (23.7%) PVs [10/44 (22.7%) in BRCA1 and 8/32 (25%) in BRCA2] were reported for the first time and considered to be novel PVs. Among those identified as unlikely to be of North African origin, the BRCA1 c.68_69del and BRCA1 c.5266dupC Jewish founder alleles and PVs that have been reported as recurrent/founder variants in European populations (ex: BRCA1 c.181T > G, BRCA1 c1016dupA). The most well characterized PVs are four in BRCA1 gene [c.211dupA (14.7%), c.798_799detTT (14%), c.5266dup (8.5%), c.5309G > T (7.8%), c.3279delC (4.7%)] and one in BRCA2 [c.1310_1313detAAGA (38.9%)]. The c.211dupA and c.5309G > T PVs were identified as specific founder variants in Tunisia and Morocco, accounting for 35.2% (19/54) and 20.4% (10/49) of total established BRCA1 PVs, respectively. c.798_799delTT variant was identified in 14% (18/129) of all BRCA1 North African carriers, suggesting a founder allele. A broad spectrum of recurrent variants including BRCA1 3279delC, BRCA1 c.5266dup and BRCA2 c.1310_1313detAAGA was detected in 42 patients. BRCA1 founder variants explain around 36.4% (47/129) of BC and outnumber BRCA2 founder variants by a ratio of ≈ 3:1. Conclusion Testing BC and/or OC patients for the panel of specific and recurrent/founder PVs might be the most cost-effective molecular diagnosis strategy.

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“…To date, published studies on the contribution of BRCA1/2 mutations to BC in the Moroccan population are still limited. Only a partially characterized BRCA1 mutation landscape in BC Moroccans is available and includes the following deleterious mutations: c.68-69delAG, c.116G > A, c.181 T > G, c.798-799delTT, c.1016dupA, c.2126insA, c.2805delA, c.3279delC, c.3453delT, c.4942A > T, c.5062-5064delGTT and c.5095C > T [ 16 – 19 ]. The main pathogenic mutations detected in BRCA2 gene were c.289G > T, c.517-1G > A, c.1310_1313delAAGA, c.3381delT, c.3847_3848delGT, c.5073dupA, c.5116_5119delAATA, c.5576-5579delTTAA, c.6428C > A, c.7110delA and c.7234_7235insG [ 16 , 17 , 19 – 21 ].…”

Section: Introductionmentioning

confidence: 99%

Increased prevalence of the founder BRCA1 c.5309G>T and recurrent BRCA2 c.1310_1313delAAGA mutations in breast cancer families from Northerstern region of Morocco: evidence of geographical specificity and high relevance for genetic counseling

Melki

Melloul

Aissaoui³

et al. 2023

BMC Cancer

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Background Inherited mutations in the breast cancer susceptibility genes BRCA1 and BRCA2 (BRCA1/2) confer high risks of breast and ovarian cancer. Because the contribution of BRCA1/2 germline mutations to BC in the Northeastern population of Morocco remains largely unknown, we conducted this first study to evaluate the prevalence and the phenotypic spectrum of two BRCA1/2 pathogenic mutations (the founder BRCA1 c.5309G>T and BRCA2 c.1310_1313delAAGA). This choice was also argued by the presence of an apparent specific geographical connection of these mutations and the Northeastern region of Morocco. Methods Screening for the germline mutations c.5309G>T and BRCA2 c.1310_1313delAAGA was performed by sequencing on a total of 184 breast cancer (BC) patients originated from the Northeastern region of Morocco. The likelihood of identifying a BRCA mutation is calculated using the Eisinger scoring model. The clinical and pathologic features were compared between the BRCA-positive and BRCA-negative groups of patients. Difference in survival outcomes was compared between mutation carriers and non-carriers. Results BRCA1 c.5309G>T and BRCA2 c.1310_1313delAAGA are responsible for a significant proportion of all BC cases (12.5%) and at least 20% of familial BC. The screening of BRCA1/2 genes by NGS sequencing confirmed that there are no additional mutations detected among positive patients. The clinicopathological features in positive patients were in accordance with typical characteristics of BRCA pathogenic mutations. The mean features in the carriers were the early onset of the disease, familial history, triple negative status (for BRCA1 c.5309G>T) and worse prognosis in terms of overall surviving. Our study indicates that the Eisinger scoring model could be recommended to identify patients for referral to BRCA1/2 oncogenetic counseling. Conclusion Our findings suggest that BRCA1 c.5309G>T and BRCA2 c.1310_1313delAAGA mutations may have a strong founder and/or recurrent effect on breast cancer among the Northeastern Moroccan population. There contribution to breast cancer incidence is certainly substantial in this subgroup. Therefore, we believe that BRCA1 c.5309G>T and BRCA2 c.1310_1313delAAGA mutations have to be included in the array of tests aimed at revealing cancer syndrome carriers among subjects of Moroccan origin.

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Contribution of BRCA1 and BRCA2 germline mutations to early onset breast cancer: a series from north of Morocco

Cited by 14 publications

References 55 publications

Novel and recurrent BRCA1/BRCA2 germline mutations in patients with breast/ovarian cancer: a series from the south of Tunisia

Novel and recurrent BRCA1/BRCA2 germline mutations in patients with breast/ovarian cancer: a series from the south of Tunisia

Prevalence of specific and recurrent/founder pathogenic variants in BRCA genes in breast and ovarian cancer in North Africa

Increased prevalence of the founder BRCA1 c.5309G>T and recurrent BRCA2 c.1310_1313delAAGA mutations in breast cancer families from Northerstern region of Morocco: evidence of geographical specificity and high relevance for genetic counseling

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