Identification of a founder <i><scp>BRCA1</scp></i> mutation in the Moroccan population

Quiles, Francisco; Teulé, Alexandre; Tandstad, N. Martinussen; Feliubadaló, Lídia; Tornero, Eva; Valle, Jesús Del; Menéndez, Mireia; Salinas, Mónica; Rognlien, Vibeke Wethe; Velasco, Ángela; Izquierdo, Àngel; Capellà, Gabriel; Brunet, Joan; Lázaro, Conxi

doi:10.1111/cge.12747

Cited by 14 publications

(15 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another novel founder, BRCA2 mutation, was identified by var der Merwe et al ( 53 ) in the Bantu-speaking Xhosa population (South Africa). Other studies have identified new BRCA mutations and their contribution to early-onset and sporadic breast and/or ovarian cancer in Arabic speaking countries ( 57 ) of Egypt ( 58 ), Tunisia ( 51 , 59 – 66 ), Algeria ( 67 – 69 ), Morocco ( 70 – 72 ), and Sudan ( 73 , 74 ), in addition to Senegal ( 75 ), Mauritius ( 76 ) and South Africa ( 50 , 77 – 79 ) in the Sub-Saharan region.…”

Section: Resultsmentioning

confidence: 99%

A Review of Cancer Genetics and Genomics Studies in Africa

Rotimi

Salhia

2021

Front. Oncol.

View full text Add to dashboard Cite

Cancer is the second leading cause of death globally and is projected to overtake infectious disease as the leading cause of mortality in Africa within the next two decades. Cancer is a group of genomic diseases that presents with intra- and inter-population unique phenotypes, with Black populations having the burden of morbidity and mortality for most types. At large, the prevention and treatment of cancers have been propelled by the understanding of the genetic make-up of the disease of mostly non-African populations. By the same token, there is a wide knowledge gap in understanding the underlying genetic causes of, and genomic alterations associated with, cancer among black Africans. Accordingly, we performed a review of the literature to survey existing studies on cancer genetics/genomics and curated findings pertaining to publications across multiple cancer types conducted on African populations. We used PubMed MeSH terms to retrieve the relevant publications from 1990 to December 2019. The metadata of these publications were extracted using R text mining packages: RISmed and Pubmed.mineR. The data showed that only 0.329% of cancer publications globally were on Africa, and only 0.016% were on cancer genetics/genomics from Africa. Although the most prevalent cancers in Africa are cancers of the breast, cervix, uterus, and prostate, publications representing breast, colorectal, liver, and blood cancers were the most frequent in our review. The most frequently reported cancer genes were BRCA1, BRCA2, and TP53. Next, the genes reported in the reviewed publications’ abstracts were extracted and annotated into three gene ontology classes. Genes in the cellular component class were mostly associated with cell part and organelle part, while those in biological process and molecular function classes were mainly associated with cell process, biological regulation, and binding, and catalytic activity, respectively. Overall, this review highlights the paucity of research on cancer genomics on African populations, identified gaps, and discussed the need for concerted efforts to encourage more research on cancer genomics in Africa.

show abstract

Section: Resultsmentioning

confidence: 99%

A Review of Cancer Genetics and Genomics Studies in Africa

Rotimi

Salhia

2021

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…13 In Africa, founder mutations have been reported in Yoruba population from Nigeria (c.303T>G; (p.Tyr101Ter)) in a series of four families, 13 in Afrikaners from South Africa (c.2641G>T (p.Glu881Ter)) 14 in five families, and in Morocco (c.5309G>T; (p.Gly1770Val)) in five families. 11 The founding effect of the variant c.815_824dup10 was reported first in five nonrelated families from US 20 and the mutation was supposed to be of West African origin.…”

Section: Discussionmentioning

confidence: 99%

Evidence for an ancient BRCA1 pathogenic variant in inherited breast cancer patients from Senegal

et al. 2020

View full text Add to dashboard Cite

BRCA1 and BRCA2 are the most incriminated genes in inherited breast/ovarian cancers. Several pathogenic variants of these genes conferring genetic predisposition have been described in different populations but rarely in sub-Saharan Africa. The objectives of this study were to identify pathogenic variants of the BRCA genes involved in hereditary breast cancer in Senegal and to search for a founder effect. We recruited after free informed consent, 27 unrelated index cases diagnosed with breast cancer and each having a family history. Mutation screening of the genes identified a duplication of ten nucleotides c.815_824dupAGCCATGTGG, (p. Thr276Alafs) (NM_007294.3) located in exon 11 of BRCA1 gene, in 15 index cases (allelic frequency 27.7%). The pathogenic variant has been previously reported in African Americans as a founder mutation of West African origin. Haplotypes analysis of seven microsatellites surrounding the BRCA1 gene highlights a shared haplotype encompassing~400 kb between D17S855 and D17S1325. This haplotype was not detected in none of 15 healthy controls. Estimation of the age of the pathogenic variant suggested that it occurred~1400 years ago. Our study identified a founder pathogenic variant of BRCA1 predisposing to breast cancer and enabled the establishment of an affordable genetic test as a mean of prevention for Senegalese women at risk.npj Genomic Medicine (2020) 5:8 ; https://doi.

show abstract

“…BRCA1 c.5266dup and, c.181 T > G as well the Ashkenazi Jewish founders are all present in the groups of low or moderately frequent mutations in our study. A recently identified Moroccan BRCA1 variant has been demonstrated in three families at OUH and have been shown to share the same haplotype as in a series of Moroccan patients [ 23 ]. Systematic collection of information on geographic or ethnic origin per individual/family was beyond the scope and permits of this study, but was performed in 2007, where it was found to be an apparent geographical connection for some of the frequent mutations in BRCA1 and BRCA2 [ 17 ] .…”

Section: Discussionmentioning

confidence: 99%

BRCA1 and BRCA2 mutation spectrum – an update on mutation distribution in a large cancer genetics clinic in Norway

Heramb

Wangensteen

Grindedal

et al. 2018

Hered Cancer Clin Pract

View full text Add to dashboard Cite

BackgroundFounder mutations in the two breast cancer genes, BRCA1 and BRCA2, have been described in many populations, among these are Ashkenazi-Jewish, Polish, Norwegian and Icelandic. Founder mutation testing in patients with relevant ancestry has been a cost-efficient approach in such populations. Four Norwegian BRCA1 founder mutations were defined by haplotyping in 2001, and accounted for 68% of BRCA1 mutation carriers at the time. After 15 more years of genetic testing, updated knowledge on the mutation spectrum of both BRCA1 and BRCA2 in Norway is needed. In this study, we aim at describing the mutation spectrum and frequencies in the BRCA1/2 carrier population of the largest clinic of hereditary cancer in Norway.MethodsA total of 2430 BRCA1 carriers from 669 different families, and 1092 BRCA2 carriers from 312 different families were included in a quality of care study. All variants were evaluated regarding pathogenicity following ACMG/ENIGMA criteria. The variants were assessed in AlaMut and supplementary databases to determine whether they were known to be founder mutations in other populations.ResultsThere were 120 different BRCA1 and 87 different BRCA2 variants among the mutation carriers. Forty-six per cent of the registered BRCA1/2 families (454/981) had a previously reported Norwegian founder mutation. The majority of BRCA1/2 mutations (71%) were rare, each found in only one or two families. Fifteen per cent of BRCA1 families and 25% of BRCA2 families had one of these rare variants. The four well-known Norwegian BRCA1 founder mutations previously confirmed through haplotyping were still the four most frequent mutations in BRCA1 carriers, but the proportion of BRCA1 mutation carriers accounted for by these mutations had fallen from 68 to 52%, and hence the founder effect was weaker than previously described.ConclusionsThe spectrum of BRCA1 and BRCA2 mutations in the carrier population at Norway’s largest cancer genetics clinic is diverse, and with a weaker founder effect than previously described. As a consequence, retesting the families that previously have been tested with specific tests/founder mutation tests should be a prioritised strategy to find more mutation positive families and possibly prevent cancer in healthy relatives.

show abstract

Identification of a founder BRCA1 mutation in the Moroccan population

Cited by 14 publications

References 18 publications

A Review of Cancer Genetics and Genomics Studies in Africa

A Review of Cancer Genetics and Genomics Studies in Africa

Evidence for an ancient BRCA1 pathogenic variant in inherited breast cancer patients from Senegal

BRCA1 and BRCA2 mutation spectrum – an update on mutation distribution in a large cancer genetics clinic in Norway

Contact Info

Product

Resources

About