The spectrum of
            <i>BRCA1</i>
            and
            <i>BRCA2</i>
            pathogenic sequence variants in Middle Eastern, North African, and South European countries

Laitman, Yael; Friebel, Tara M.; Yannoukakos, Drakoulis; Fostira, Florentia; Konstantopoulou, Irene; Figlioli, Gisella; Bonanni, Bernardo; Manoukian, Siranoush; Zuradelli, Monica; Tondini, Carlo; Pasini, Barbara; Peterlongo, Paolo; Plaseska‐Karanfilska, Dijana; Jakimovska, Milena; Majidzadeh, Keivan; Zarinfam, Shiva; Loizidou, Maria A.; Hadjisavvas, Andreas; Michailidou, Kyriaki; Kyriacou, Kyriacos; Behar, Doron M.; Bernstein‐Molho, Rinat; Ganz, Patricia A.; James, Paul; Parsons, Michael T.; Sallam, Aminah; Olopade, Olufunmilayo I.; Seth, Arun; Chenevix-Trench, Georgia; Leslie, Goska; McGuffog, Lesley; Marafie, Makia J.; Mégarbané, André; Al-Mulla, Fahd; Rebbeck, Timothy R.; Friedman, Eitan

doi:10.1002/humu.23842

Cited by 41 publications

(35 citation statements)

References 37 publications

(71 reference statements)

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“…Establishing the mutational profile in our region will allow directed testing of high-risk families, therefore increasing the benefit while reducing costs. This is an agreement with Laitman et al who identified several highly-recurring mutations in the region 13 .…”

Section: Discussionsupporting

confidence: 93%

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BRCA1 and BRCA2 genes mutations among high risk breast cancer patients in Jordan

Abu-Helalah

Azab

Mubaidin

et al. 2020

Sci Rep

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Familial breast cancer is estimated to account for 15–20% of all cases of breast cancer. Surveillance for familial breast cancer is well-established world-wide. However, this service does not exist in Jordan, due to the scarcity of information with regard to the genetic profiling of these patients, and therefore lack of recommendations for policy-makers. As such, patients with very strong family history of breast or ovarian cancers are not screened routinely; leading to preventable delay in diagnosis. Whole coding sequencing for BCRA1/BCRA2 using next-generation sequencing (NGS)/Ion PGM System was performed. Sanger sequencing were then used to confirm the pathogenic variants detected by NGS. In this study, 192 breast cancer patients (and 8 ovarian cancer cases) were included. The prevalence of recurrent pathogenic mutations was 14.5%, while the prevalence of newly detected mutations was 3.5%. Two novel pathogenic mutations were identified in BRCA2 genes. The common mutations in the Ashkenazi population used for screening may not apply in the Jordanian population, as previously reported mutations were not prevalent, and other new mutations were identified. These data will aid to establish a specific screening test for BRCA 1/BRCA2 in the Jordanian population.

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Section: Discussionsupporting

confidence: 93%

“…Recently, a comprehensive assessment of the mutational spectrum of BRCA1 / BRCA2 in the Middle East, North Africa, and Southern Europe was published 13 . Laitamn et al reported recurring pathogenic sequence variants (PSVs) identifying 232 PSVs and 239 PSVs in BRCA1 and BRCA2 , respectively.…”

Section: Introductionmentioning

confidence: 99%

BRCA1 and BRCA2 genes mutations among high risk breast cancer patients in Jordan

Abu-Helalah

Azab

Mubaidin

et al. 2020

Sci Rep

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“…In BRCA1gene, we identi ed the c.5030_5033delCTAA mutation in 3 out of 15 (20%) unrelated patients with early onset familial. This mutation has not been reported in North Africa but was found in patients from Greece, Italy, Jordan, Lebanon, Kuwait, and Saudia Arabia [15]. In addition, the nonsens mutation c.2338C > T was shared by 2 young patients (< 50 years-old) diagnosed with ovarian cancer.…”

Section: Discussionmentioning

confidence: 80%

“…BRCA1 and BRCA2 have key roles in the development of breast/ovarian cancer [9,10]. The prevalence of BRCA1/BRCA2 mutations varies in different populations due to founder mutation effect [15,[24][25][26][27][28]. Genetic testing of patients with family history for breast/ovarian cancer have become standard clinical management in Western countries, however, in Tunisia studies of BRCA-associated breast/ovarian cancer remain less investigated.…”

Section: Discussionmentioning

confidence: 99%

“…Despite the importance of the mutational spectrum of BRCA1/BRCA2 genes, only few studies using Sanger DNA sequencing, investigated Tunisian patients with familial breast/ovarian cancers. In a recent study, Laitamn et al reported all the pathogenic variants in both BRCA1 and BRCA2 genes in the Middle East, North Africa, and Southern Europe [15]. The authors identi ed 232 and 239 pathogenic sequence variants in BRCA1 and BRCA2, respectively that include only few variants that were found in Tunisian patients [15].…”

Section: Introductionmentioning

confidence: 99%

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Novel and Recurrent BRCA1/BRCA2 Germline Mutations in Patients with Breast /Ovarian Cancer: A Series from the South of Tunisia

Ayed-Guerfali

Kridis-Rejab

Ammous-Boukhris

et al. 2020

Preprint

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Background: The incidence of breast/ovarian cancer 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 breast/ovarian cancer. 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 frameshisft indel (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 (31-40 y and 41-50 y), 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 breast/ovarian cancer.

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Strong founder effect for BRCA1 c.3629_3630delAG pathogenic variant in Chechen patients with breast or ovarian cancer

et al. 2022

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Coding sequences of BRCA1, BRCA2, ATM, TP53, and PALB2 genes were analyzed in 68 consecutive Chechen patients with high‐grade serous ovarian cancer (HGSOC). Pathogenic BRCA1/2 variants were identified in 15 (22%) out of 68 HGSOC cases. Nine out of ten patients with BRCA1 pathogenic alleles carried the same deletion (c.3629_3630delAG), and three out of five BRCA2 heterozygotes had Q3299X allele. The analysis of 49 consecutive patients with triple‐negative breast cancer (TNBC) revealed 3 (6%) additional BRCA1 heterozygotes. All women with BRCA1 c.3629_3630delAG allele also carried linked c.1067G>A (Q356R) single nucleotide polymorphism, indicating that this is a genuine founder variant but not a mutational hotspot. An ATM truncating allele was detected in one HGSOC patient. There were no women with TP53 or PALB2 germline alterations. Genetic analysis of non‐selected HGSOC patients is an efficient tool for the identification of ethnicity‐specific BRCA1/2 pathogenic variants.

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The spectrum of BRCA1 and BRCA2 pathogenic sequence variants in Middle Eastern, North African, and South European countries

Cited by 41 publications

References 37 publications

BRCA1 and BRCA2 genes mutations among high risk breast cancer patients in Jordan

BRCA1 and BRCA2 genes mutations among high risk breast cancer patients in Jordan

Novel and Recurrent BRCA1/BRCA2 Germline Mutations in Patients with Breast /Ovarian Cancer: A Series from the South of Tunisia

Strong founder effect for BRCA1 c.3629_3630delAG pathogenic variant in Chechen patients with breast or ovarian cancer

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