A novel BRCA-1 mutation in Arab kindred from east Jerusalem with breast and ovarian cancer

Kadouri, Luna; Bercovich, Dani; Elimelech, Arava; Lerer, Israela; Sagi, Michal; Glusman, Gila; Shochat, Chen; Korem, Sigal; Hamburger, Tamar; Nissan, Aviram; Abu-Halaf, Nahil; Badrriyah, Muhmud; Abeliovich, Dvorah; Peretz, Tamar

doi:10.1186/1471-2407-7-14

Cited by 31 publications

(21 citation statements)

References 10 publications

(14 reference statements)

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“…The low age of onset was also reported in other Asian countries, and Arab countries in the Middle East [24-26]. It may be explained by the differences in exposure to female hormones, diet, physical activity, or other factors.…”

Section: Discussionmentioning

confidence: 60%

Prevalance of BRCA1 and BRCA2 mutations in familial breast cancer patients in Lebanon

Jalkh

Nassar-Slaba

Chouery

et al. 2012

Hered Cancer Clin Pract

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Breast cancer is the most prevalent malignancy in women in Western countries, currently accounting for one third of all female cancers. Familial aggregation is thought to account for 5–10 % of all BC cases, and germline mutations in BRCA1 and BRCA2 account for less of the half of these inherited cases. In Lebanon, breast cancer represents the principal death-causing malignancy among women, with 50 % of the cases diagnosed before the age of 50 years. In order to study BRCA1/2 mutation spectra in the Lebanese population, 72 unrelated patients with a reported family history of breast and/or ovarian cancers or with an early onset breast cancer were tested. Fluorescent direct sequencing of the entire coding region and intronic sequences flanking each exon was performed. A total of 38 BRCA1 and 40 BRCA2 sequence variants were found. Seventeen of them were novel. Seven confirmed deleterious mutations were identified in 9 subjects providing a frequency of mutations of 12.5 %. Fifteen variants were considered of unknown clinical significance according to BIC and UMD-BRCA1/BRCA2 databases. In conclusion, this study represents the first evaluation of the deleterious and unclassified genetic variants in the BRCA1/2 genes found in a Lebanese population with a relatively high risk of breast cancer.

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Section: Discussionmentioning

confidence: 60%

Prevalance of BRCA1 and BRCA2 mutations in familial breast cancer patients in Lebanon

Jalkh

Nassar-Slaba

Chouery

et al. 2012

Hered Cancer Clin Pract

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“…Of the mutations previously reported in the literature, BRCA1 p.E1373X, BRCA2 c.2482delGACT, and TP53 p.R181C have been reported in other Palestinian families. [8,9,10] BRCA1 p.C44F and BRCA1 p.W1815X were originally described in Lebanese families. [11,12] XRCC2 p. R215X was originally described in a child with Fanconi anemia living in Saudi Arabia.…”

Section: Resultsmentioning

confidence: 99%

Genomic analysis of inherited breast cancer among Palestinian women: Genetic heterogeneity and a founder mutation in TP53

Hamameh

Renbaum

Kamal

et al. 2017

Intl Journal of Cancer

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Breast cancer among Palestinian women has lower incidence than in Europe or North America, yet is very frequently familial. We studied genetic causes of this familial clustering in a consecutive hospital-based series of 875 Palestinian patients with invasive breast cancer, including 453 women with diagnosis by age 40, or with breast or ovarian cancer in a mother, sister, grandmother, or aunt (“discovery series”); and 422 women diagnosed after age 40 and with negative family history (“older-onset sporadic patient series”). Genomic DNA from women in the discovery series was sequenced for all known breast cancer genes, revealing a pathogenic mutation in 13% (61/453) of patients. These mutations were screened in all patients and in 300 Palestinian female controls, revealing 1.0% (4/422) carriers among older, non-familial patients and two carriers among controls. The mutational spectrum was highly heterogeneous, including pathogenic mutations in eleven different genes: BRCA1, BRCA2, TP53, ATM, CHEK2, BARD1, BRIP1, PALB2, MRE11A, PTEN, and XRCC2. BRCA1 carriers were significantly more likely than other patients to have triple negative tumors (P = 0.03). The single most frequent mutation was TP53 p.R181C, which was significantly enriched in the discovery series compared to controls (P = 0.01) and was responsible for 15% of breast cancers among young onset or familial patients. TP53 p.R181C predisposed specifically to breast cancer with incomplete penetrance, and not to other Li-Fraumeni cancers. Palestinian women with young onset or familial breast cancer and their families would benefit from genetic analysis and counseling.

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“…This is the most comprehensive analysis published to date on high risk families of these origins. Overall, there are only a handful of germline mutations among Moslem women that were reported world-wide, with a paucity of data about the Palestinian population: an inactivating mutation (E1373X) in BRCA1 [18] another clearly pathogenic mutation (2482delGACT) in BRCA2 [17] and several missense mutations of unknown pathogenic significance in our own previously published series [29].…”

Section: Discussionmentioning

confidence: 99%

“…Early age at diagnosis is suggestive of an inherited predisposition to breast cancer. However, there are only few reports on the spectrum of BRCA1 and BRCA2 mutations among Arab-Moslem women [17][18][19][20][21][22][23][24][25][26]. Furthermore, given the Moslem Arab traditions and practices, it seemed plausible that several founder mutations may underlie inherited predisposition in that population.…”

Section: Introductionmentioning

confidence: 98%

Germline mutations in BRCA1 and BRCA2 genes in ethnically diverse high risk families in Israel

Laitman

Borsthein

Stoppa‐Lyonnet

et al. 2010

Breast Cancer Res Treat

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Three mutations in BRCA1 (185delAG, 5382InsC) and BRCA2 (6174delT) predominate among high risk breast ovarian cancer Ashkenazi Jewish families, with few "private" mutations described. Additionally, the spectrum of BRCA1 and BRCA2 germline mutations among high risk Jewish non Ashkenazi and non Jewish Israelis is undetermined. Genotyping by exon-specific sequencing or heteroduplex analysis using enhanced mismatch mutation analysis was applied to 250 high risk, predominantly cancer affected, unrelated Israeli women of Ashkenazi (n = 72), non Ashkenazi (n = 90), Moslem (n = 45), Christian Arabs (n = 21), Druze (n = 17), and non Jewish Caucasians (n = 5). All Jewish women were prescreened and did not harbor any of the predominant BRCA1 or BRCA2 Jewish mutations. Age at diagnosis of breast cancer (median ± SD) (n = 219) was 40.1 ± 11.7, 45.6 ± 10.7, 38.7 ± 9.2, 45.5 ± 11.4 ± and 40.7 ± 8.1 years for Ashkenazi, non Ashkenazi, Moslem, Christian, and Druze participants, respectively. For ovarian cancer (n = 19) the mean ages were 45.75 ± 8.2, 57.9 ± 10.1, 54 ± 8, 70 ± 0, and 72 ± 0 for these origins, respectively. Overall, 22 (8.8%) participants carried 19 clearly pathogenic mutations-10 BRCA1 and 9 BRCA2 (3 novel): 3 in Ashkenazim, 6 in 8 non-Ashkenazim, 6 in 7 Moslems, 2 in Druze, and 2 in non Jewish Caucasians. Only three mutations (c.1991del4, C61G, A1708E) were detected in 2 seemingly unrelated families of Moslem and non- Ashkenazi origins. There were no inactivating mutations among 55 Ashkenazi high risk breast cancer only families. In conclusion, there are no predominant recurring germline mutations in BRCA1 or BRCA2 genes among ethnically diverse Jewish and non Jewish high risk families in Israel.

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A novel BRCA-1 mutation in Arab kindred from east Jerusalem with breast and ovarian cancer

Cited by 31 publications

References 10 publications

Prevalance of BRCA1 and BRCA2 mutations in familial breast cancer patients in Lebanon

Prevalance of BRCA1 and BRCA2 mutations in familial breast cancer patients in Lebanon

Genomic analysis of inherited breast cancer among Palestinian women: Genetic heterogeneity and a founder mutation in TP53

Germline mutations in BRCA1 and BRCA2 genes in ethnically diverse high risk families in Israel

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