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

Ansari, Fatima Zahra El; Jouali, Farah; Marchoudi, Nabila; Bennani, Mohcine; Ghailani, Naima; Barakat, Amina; Fekkak, Jamal

doi:10.1186/s12885-020-07250-0

Cited by 16 publications

(19 citation statements)

References 66 publications

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“…The retrieved articles describe studies conducted in Morocco (n=11) [ 8 – 18 ], Algeria (n=5) [ 19 – 23 ], and Tunisia (n=9) [ 24 – 32 ]. Overall, 15 studies investigated both BRCA1 and BRCA2 genes [ 8 , 9 , 12 , 15 – 18 , 20 – 22 , 25 – 27 , 29 , 31 , 32 ], four studies examined the entire coding regions of the BRCA1 gene [ 10 , 19 , 24 , 30 ], and six studies in which the analysis was restricted to a few BRCA1 and/or BRCA2 exons [ 11 , 13 , 14 , 23 , 28 ].…”

Section: Resultsmentioning

confidence: 99%

“… 15 ? - 2 Algeria 1 BOC,1 BC Familial [ 23 ] c.5030_5033delCTAA 15 NS p.Thr1677Ilefs2 3 Tunisia 1 BOC,2 OC Familial [ 32 ] c.4823C>G 16 NS p.Ser1608Ter 1 Morocco BC Familial [ 15 ] c.4942A>T 16 NS p.Lys1648X 1 Morocco BC Sporadic [ 10 ] c.5062_5064delGTT 17 FS p.Val1688del 1 Morocco BC Familial [ 9 ] c.5117G>C 18 MS p.Gly1706Ala 1 Algeria BC Familial [ 22 ] c.5158C>T 18 MS p.Arg1720Trp 1 Morocco BC Familial [ 15 ] c.5266dupC 20 FS p.Gln1756Profs 11 Tunisia 9 BC, 2 BOC Familial [ 24 – 28 , 30 ] c.5309G>T 20 MS p.Gly1770Val 10 Morocco 9BC,1 OC, 8 Familial 2 Sporadic [ 13 , …”

Section: Resultsmentioning

confidence: 99%

“…The most well characterized five PVs are four in BRCA1 gene including c.211dupA (14.7%, 19/129) [ 24 , 25 , 27 , 28 , 31 ], c.798_799detTT (14%, 18/129) [ 9 , 10 , 15 – 18 , 20 , 24 , 29 , 30 ], c.5266dup (8.5%, 11/129) [ 24 – 28 , 30 ], c.5309G>T (7.8%, 10/129) [ 13 , 17 ], c.3279delC (4.7%, 6/129) [ 9 , 11 , 15 ] and one in BRCA2 including c.1310_1313detAAGA (38.9%, 26/67) [ 12 , 14 , 20 , 28 , 32 ]. The BRCA1 c.798_799delTT was identified in 18 North African patients, accounting for 14% (18/129) of the total identified BRCA1 PVs [ 9 , 10 , 15 – 20 , 24 , 29 , 30 ]. Microsatellite markers in and flanking the BRCA1 locus showed a common haplotype in Algerian and Tunisian c.798_799delTT carriers, suggesting the first non-Jewish founder variant to be described in Northern Africa [ 19 ].…”

Section: Resultsmentioning

confidence: 99%

“…The BRCA1 c.3279delC variant mutation is a recurring PV in the Moroccan population. It accounts for 12.2% (6/49) of the BRCA1 mutations [ 9 , 11 , 15 ], suggesting a possible founder effect. This mutation has been identified in one HBOC kindred of Dutch descent as well as in one HBOC kindred of Moroccan descent in which the proband and her mother were diagnosed with BC at younger ages [ 9 , 37 ].…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2022

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Background Elucidation of specific and recurrent/founder pathogenic variants (PVs) in BRCA (BRCA1 and BRCA2) genes can make the genetic testing, for breast cancer (BC) and/or ovarian cancer (OC), affordable for developing nations. 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 and32 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. Conclusions 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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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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

et al. 2022

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“…The hereditary breast and ovarian cancer (HBOC) syndrome is an autosomal dominant inherited disorder that includes 5%-7% of all breast cancer (BC) cases and 10%-15% of all ovarian cancer (OC) cases. 1 Although the majority of BC and OC cases are sporadic (75%-80%), ~15%-20% are considered familial type and 5%-10% are hereditary. 2 , 3 Moreover, ~3%-10% of patients with pancreatic adenocarcinoma exhibit a family history of pancreatic cancer (PC) and ~10%-20% are due to a hereditary cause.…”

Section: Introductionmentioning

confidence: 99%

Impact of deleterious variants in other genes beyond BRCA1/2 detected in breast/ovarian and pancreatic cancer patients by NGS-based multi-gene panel testing: looking over the hedge

et al. 2021

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Background Hereditary breast cancer (BC), ovarian cancer (OC), and pancreatic cancer (PC) are the major BRCA -associated tumours. However, some BRCA1/2 -wild-type (wt) patients with a strong personal and/or family history of cancer need a further genetic testing through a multi-gene panel containing other high- and moderate-risk susceptibility genes. Patients and methods Our study was aimed to assess if some BC, OC, or PC patients should be offered multi-gene panel testing, based on well-defined criteria concerning their personal and/or family history of cancer, such as earliness of cancer onset, occurrence of multiple tumours, or presence of at least two or more affected first-degree relatives. For this purpose, 205 out of 915 BC, OC, or PC patients, resulted negative for BRCA1/2 and with significant personal and/or family history of cancer, were genetically tested for germline pathogenic or likely pathogenic variants (PVs/LPVs) in genes different from BRCA1/2 . Results Our investigation revealed that 31 (15.1%) out of 205 patients harboured germline PVs/LPVs in no- BRCA genes, including PALB2 , CHEK2 , ATM , MUTYH , MSH2 , and RAD51C . Interestingly, in the absence of an analysis conducted through multi-gene panel, a considerable percentage (15.1%) of PVs/LPVs would have been lost. Conclusions Providing a multi-gene panel testing to BRCA1/2 -wt BC/OC/PC patients with a strong personal and/or family history of cancer could significantly increase the detection rates of germline PVs/LPVs in other cancer predisposition genes beyond BRCA1/2. The use of a multi-gene panel testing could improve the inherited cancer risk estimation and clinical management of patients and unaffected family members.

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Breast cancer in East Africa: Prevalence and spectrum of germline SNV/indel and CNVs in BRCA1 and BRCA2 genes among breast cancer patients in Tanzania

et al. 2022

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Background Growing prevalence and aggressiveness of breast cancer (BC) among East African women strongly indicate that the genetic risk factor implicated in the etiology of the disease may have a key role. Germline pathogenic variants in BRCA1 and BRCA2 ( BRCA1/2 ) are known to increase the lifetime risk of BC. This study investigated the prevalence and spectrum of germline single nucleotide variant/insertion and deletion (SNV/indel), and copy number variations (CNVs) in BRCA1/2 among Tanzanian BC patients, and evaluated the associations of identified variants with patient's socio‐demographic and histopathological characteristics. Methods One hundred BC patients were examined for BRCA1/2 variants using next‐generation sequencing (NGS). Sanger sequencing and multiplex ligation‐dependent probe amplification (MLPA) assay were performed for the confirmation of SNV/indel and CNVs, respectively. Results Six germline SNV/indel pathogenic variants were detected from six unrelated patients. Five of these variants were identified in BRCA1 , and one in BRCA2 . We also identified, in one patient, one variant of uncertain clinical significance (VUS). CNV was not detected in any of the BC patients. Furthermore, we found that in our cohort, BRCA1/2 variant carriers were triple‐negative BC patients ( p = 0.019). Conclusions Our study provides first insight into BC genetic landscape by the use of NGS in the under‐represented East African Tanzanian populations. Our findings support the importance of genetic risk factors in BC etiology in Tanzania and showed a relatively high overall prevalence (6%) of germline BRCA1/2 pathogenic variants in BC patients. Therefore, our results indicate that BRCA1/2 pathogenic variants may well contribute to BC incidence in Tanzania. Thus, the identification of frequent variants in BRCA1/2 genes will enable implementation of rapid, inexpensive population‐specific BRCA1/2 genetic testing, particularly for triple‐negative BC patients known for their high prevalence in Tanzania. This will, in turn, greatly contributes to provide effective therapeutic strategies.

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

Cited by 16 publications

References 66 publications

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

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

Impact of deleterious variants in other genes beyond BRCA1/2 detected in breast/ovarian and pancreatic cancer patients by NGS-based multi-gene panel testing: looking over the hedge

Breast cancer in East Africa: Prevalence and spectrum of germline SNV/indel and CNVs in BRCA1 and BRCA2 genes among breast cancer patients in Tanzania

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