{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T23:02:59Z","timestamp":1773356579603,"version":"3.50.1"},"reference-count":58,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,9,7]],"date-time":"2020-09-07T00:00:00Z","timestamp":1599436800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,9,7]],"date-time":"2020-09-07T00:00:00Z","timestamp":1599436800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Cancer"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>To date, the contribution of BRCA1\/2 mutations in Moroccan early onset breast cancer patients remains unknown. Here we assess these genetic alterations for the first time in a cohort from North of Morocco.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Thirty-three patients diagnosed with breast cancer at the age of \u226440\u2009years were recruited irrespective of breast and\/or ovarian cancer family history. Coding regions and intron-exon boundaries of BRCA1 and BRCA2 genes were sequenced from peripheral blood DNA using Ion Proton (Thermo Fisher Scientific) next generation sequencing platform.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Overall, five BRCA germline mutations were identified (15.1%). The frequency of mutations among patients with family history of breast cancer was 16.7%. Three mutations were found in BRCA1 (9%) and two within the BRCA2 gene (6%). These are three frameshift mutations (c.798_799del, c.2125_2126insA, c.5116_5119delAATA), one missense (c.116G\u2009&gt;\u2009A) and one nonsense mutation (c.289G\u2009&gt;\u2009T). The mutation c.5116_5119delAATA has a founder effect in North Africa. Moreover, one variant of unknown significance was identified in BRCA2 (c.4090A\u2009&gt;\u2009G). Most BRCA mutations carriers (80%) had no family history of breast cancer.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Our data do not support the hypothesis that BRCA mutations alone explain the higher frequency of breast cancer in Moroccan young women. The young age (\u226440\u2009years) for breast cancer diagnosis seems to be strongly predictive of BRCA mutation status in Moroccan patients. These results will help in decision making with regard to genetic counseling and testing in the national scale.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s12885-020-07352-9","type":"journal-article","created":{"date-parts":[[2020,9,7]],"date-time":"2020-09-07T11:02:37Z","timestamp":1599476557000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Contribution of BRCA1 and BRCA2 germline mutations to early onset breast cancer: a series from north of Morocco"],"prefix":"10.1186","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5254-725X","authenticated-orcid":false,"given":"Joaira","family":"Bakkach","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed","family":"Mansouri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Touria","family":"Derkaoui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali","family":"Loudiyi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"ElMostafa","family":"El Fahime","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amina","family":"Barakat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naima","family":"Ghailani Nourouti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaime","family":"Martinez De Villarreal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Cortijo Bringas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohcine","family":"Bennani Mechita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,9,7]]},"reference":[{"key":"7352_CR1","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S1470-2045(17)30891-4","volume":"19","author":"ER Copson","year":"2018","unstructured":"Copson ER, Maishman TC, Tapper WJ, Cutress RI, Greville-Heygate S, Altman DG, et al. Germline BRCA mutation and outcome in young-onset breast cancer (POSH): a prospective cohort study. Lancet Oncol. 2018;19:169\u201380.","journal-title":"Lancet Oncol"},{"key":"7352_CR2","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1186\/s12905-017-0456-1","volume":"17","author":"J Bakkach","year":"2017","unstructured":"Bakkach J, Mansouri M, Derkaoui T, Loudiyi A, Fihri M, Hassani S, et al. Clinicopathologic and prognostic features of breast cancer in young women: a series from north of Morocco. BMC Womens Health. 2017;17:106.","journal-title":"BMC Womens Health"},{"key":"7352_CR3","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1056\/NEJM199601183340301","volume":"334","author":"AA Langston","year":"1996","unstructured":"Langston AA, Malone KE, Thompson JD, Daling JR, Ostrander EA. BRCA1 mutations in a population-based sample of young women with breast Cancer. N Engl J Med. 1996;334:137\u201342.","journal-title":"N Engl J Med"},{"key":"7352_CR4","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1093\/jnci\/91.11.943","volume":"91","author":"J Peto","year":"1999","unstructured":"Peto J, Collins N, Barfoot R, Seal S, Warren W, Rahman N, et al. Prevalence of BRCA1 and BRCA2 gene mutations in patients with early-onset breast Cancer. JNCI J Natl Cancer Inst. 1999;91:943\u20139.","journal-title":"JNCI J Natl Cancer Inst"},{"key":"7352_CR5","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1002\/(SICI)1097-0142(20000315)88:6<1393::AID-CNCR17>3.0.CO;2-P","volume":"88","author":"KE Malone","year":"2000","unstructured":"Malone KE, Daling JR, Neal C, Suter NM, O\u2019Brien C, Cushing-Haugen K, et al. Frequency ofBRCA1\/BRCA2 mutations in a population-based sample of young breast carcinoma cases. Cancer. 2000;88:1393\u2013402.","journal-title":"Cancer."},{"key":"7352_CR6","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1093\/jnci\/93.16.1215","volume":"93","author":"N Loman","year":"2001","unstructured":"Loman N, Johannsson O, Kristoffersson U, Olsson H, Borg A. Family history of breast and ovarian cancers and BRCA1 and BRCA2 mutations in a population-based series of early-onset breast cancer. J Natl Cancer Inst. 2001;93:1215\u201323.","journal-title":"J Natl Cancer Inst"},{"key":"7352_CR7","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1002\/1097-0215(20010520)95:3<189::AID-IJC1032>3.0.CO;2-N","volume":"95","author":"PN Tonin","year":"2001","unstructured":"Tonin PN, Perret C, Lambert JA, Paradis A-J, Kantemiroff T, Beno\u00eet M-H, et al. FounderBRCA1 andBRCA2 mutations in early-onset French Canadian breast cancer cases unselected for family history. Int J Cancer. 2001;95:189\u201393.","journal-title":"Int J Cancer"},{"key":"7352_CR8","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1002\/ijc.11271","volume":"106","author":"S de Sanjos\u00e9","year":"2003","unstructured":"de Sanjos\u00e9 S, L\u00e9on\u00e9 M, B\u00e9rez V, Izquierdo A, Font R, Brunet JM, et al. Prevalence of BRCA1 and BRCA2 germline mutations in young breast cancer patients: a population-based study: BRCA and breast Cancer in young women. Int J Cancer. 2003;106:588\u201393.","journal-title":"Int J Cancer"},{"key":"7352_CR9","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1002\/humu.9188","volume":"22","author":"JI Mart\u00ednez-Ferrandis","year":"2003","unstructured":"Mart\u00ednez-Ferrandis JI, Vega A, Chirivella I, Mar\u00edn-Garc\u00eda P, Insa A, Lluch A, et al. Mutational analysis of BRCA1 and BRCA2 in Mediterranean Spanish women with early-onset breast cancer: identification of three novel pathogenic mutations. Hum Mutat. 2003;22:417\u20138.","journal-title":"Hum Mutat"},{"key":"7352_CR10","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1897-4287-9-10","volume":"9","author":"C Koumpis","year":"2011","unstructured":"Koumpis C, Dimitrakakis C, Antsaklis A, Royer R, Zhang S, Narod SA, et al. Prevalence of BRCA1 and BRCA2 mutations in unselected breast cancer patients from Greece. Hered Cancer Clin Pract. 2011;9:10.","journal-title":"Hered Cancer Clin Pract"},{"key":"7352_CR11","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1016\/S0959-8049(00)00110-6","volume":"36","author":"H Anton-Culver","year":"2000","unstructured":"Anton-Culver H, Cohen PF, Gildea ME, Ziogas A. Characteristics of BRCA1 mutations in a population-based case series of breast and ovarian cancer. Eur J Cancer. 2000;36:1200\u20138.","journal-title":"Eur J Cancer"},{"key":"7352_CR12","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1634\/theoncologist.2014-0364","volume":"20","author":"NS El Saghir","year":"2015","unstructured":"El Saghir NS, Zgheib NK, Assi HA, Khoury KE, Bidet Y, Jaber SM, et al. BRCA1 and BRCA2 mutations in ethnic Lebanese Arab women with high hereditary risk breast Cancer. Oncologist. 2015;20:357\u201364.","journal-title":"Oncologist"},{"key":"7352_CR13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2016\/7869095","volume":"2016","author":"S Henouda","year":"2016","unstructured":"Henouda S, Bensalem A, Reggad R, Serrar N, Rouabah L, Pujol P. Contribution of BRCA1 and BRCA2 Germline mutations to early Algerian breast Cancer. Dis Markers. 2016;2016:1\u20137.","journal-title":"Dis Markers"},{"key":"7352_CR14","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1186\/s12885-018-4079-1","volume":"18","author":"H Abdel-Razeq","year":"2018","unstructured":"Abdel-Razeq H, Al-Omari A, Zahran F, Arun B. Germline BRCA1\/BRCA2 mutations among high risk breast cancer patients in Jordan. BMC Cancer. 2018;18:152.","journal-title":"BMC Cancer"},{"key":"7352_CR15","doi-asserted-by":"crossref","unstructured":"Ebrahimi E, Sellars E, Shirkoohi R, Harirchi I, Ghiasvand R, Mohebbi E et al. NGS-Based BRCA1, BRCA2, and PALB2 Mutation Testing in Iranian Population With Breast Cancer. J Glob Oncol. 2018; 4 suppl (2):208s-208s.","DOI":"10.1200\/jgo.18.84100"},{"key":"7352_CR16","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/j.ygyno.2012.03.007","volume":"125","author":"A Tazzite","year":"2012","unstructured":"Tazzite A, Jouhadi H, Nadifi S, Aretini P, Falaschi E, Collavoli A, et al. BRCA1 and BRCA2 germline mutations in Moroccan breast\/ovarian cancer families: novel mutations and unclassified variants. Gynecol Oncol. 2012;125:687\u201392.","journal-title":"Gynecol Oncol"},{"key":"7352_CR17","doi-asserted-by":"crossref","first-page":"60","DOI":"10.7150\/ijms.5014","volume":"10","author":"A Laraqui","year":"2013","unstructured":"Laraqui A, Uhrhammer N, Lahlou-Amine I, Rhaffouli HE, Baghdadi JE, Dehayni M, et al. Mutation screening of the BRCA1 gene in early onset and familial breast\/ovarian Cancer in Moroccan population. Int J Med Sci. 2013;10:60\u20137.","journal-title":"Int J Med Sci"},{"key":"7352_CR18","doi-asserted-by":"crossref","first-page":"791","DOI":"10.4238\/2014.January.31.5","volume":"13","author":"A Tazzite","year":"2014","unstructured":"Tazzite A, Nadiffi S, Kottwitz D, El Amrani M, Jouhadi H, Benider A, et al. Specific BRCA1 gene variations amongst young Moroccan breast cancer patients. Genet Mol Res. 2014;13:791\u20138.","journal-title":"Genet Mol Res"},{"key":"7352_CR19","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.3892\/ol.2016.4739","volume":"12","author":"F Jouali","year":"2016","unstructured":"Jouali F, Laarabi F-Z, Marchoudi N, Ratbi I, Elalaoui SC, Rhaissi H, et al. First application of next-generation sequencing in Moroccan breast\/ovarian cancer families and report of a novel frameshift mutation of the BRCA1 gene. Oncol Lett. 2016;12:1192\u20136.","journal-title":"Oncol Lett"},{"key":"7352_CR20","doi-asserted-by":"crossref","first-page":"197","DOI":"10.7150\/ijms.5.197","volume":"5","author":"N Uhrhammer","year":"2008","unstructured":"Uhrhammer N, Abdelouahab A, Lafarge L, Feillel V, Ben Dib A, Bignon Y-J. BRCA1 mutations in Algerian breast cancer patients: high frequency in young, sporadic cases. Int J Med Sci. 2008;5:197\u2013202.","journal-title":"Int J Med Sci"},{"issue":"6","key":"7352_CR21","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1155\/2010\/585278","volume":"28","author":"F Cherbal","year":"2010","unstructured":"Cherbal F, Bakour R, Adane S, Boualga K, Benais-Pont G, Maillet P. BRCA1 and BRCA2 Germline mutations screening in Algerian breast\/ovarian Cancer families. Dis Markers. 2010;28(6):377\u201384.","journal-title":"Dis Markers"},{"key":"7352_CR22","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1007\/s11033-011-0829-8","volume":"39","author":"W Mahfoudh","year":"2012","unstructured":"Mahfoudh W, Bouaouina N, Ahmed SB, Gabbouj S, Shan J, Mathew R, et al. Hereditary breast cancer in middle eastern and north African (MENA) populations: identification of novel, recurrent and founder BRCA1 mutations in the Tunisian population. Mol Biol Rep. 2012;39:1037\u201346.","journal-title":"Mol Biol Rep"},{"key":"7352_CR23","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1111\/cge.12337","volume":"87","author":"A Riahi","year":"2015","unstructured":"Riahi A, Kharrat M, Ghourabi ME, Khomsi F, Gamoudi A, Lariani I, et al. Mutation spectrum and prevalence of BRCA 1 and BRCA 2 genes in patients with familial and early-onset breast\/ovarian cancer from Tunisia: mutation spectrum and prevalence of BRCA 1 and BRCA 2 genes. Clin Genet. 2015;87:155\u201360.","journal-title":"Clin Genet"},{"key":"7352_CR24","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/1756-9966-29-82","volume":"29","author":"SS Ibrahim","year":"2010","unstructured":"Ibrahim SS, Hafez EE, Hashishe MM. Presymptomatic breast cancer in Egypt: role of BRCA1 and BRCA2 tumor suppressor genes mutations detection. J Exp Clin Cancer Res. 2010;29:82.","journal-title":"J Exp Clin Cancer Res"},{"key":"7352_CR25","doi-asserted-by":"crossref","first-page":"R6","DOI":"10.1186\/bcr443","volume":"4","author":"VR Yassaee","year":"2002","unstructured":"Yassaee VR, Zeinali S, Harirchi I, Jarvandi S, Mohagheghi MA, Hornby DP, et al. Novel mutations in the BRCA1 and BRCA2genes in Iranian women with early-onset breast cancer. Breast Cancer Res. 2002;4:R6.","journal-title":"Breast Cancer Res"},{"key":"7352_CR26","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1007\/s00432-005-0678-8","volume":"131","author":"A Pietschmann","year":"2005","unstructured":"Pietschmann A, Mehdipour P, Mehdipour P, Atri M, Hofmann W, Hosseini-Asl SS, et al. Mutation analysis of BRCA1 and BRCA2 genes in Iranian high risk breast cancer families. J Cancer Res Clin Oncol. 2005;131:552\u20138.","journal-title":"J Cancer Res Clin Oncol"},{"key":"7352_CR27","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s10689-011-9477-3","volume":"11","author":"F Keshavarzi","year":"2012","unstructured":"Keshavarzi F, Javadi GR, Zeinali S. BRCA1 and BRCA2 germline mutations in 85 Iranian breast cancer patients. Familial Cancer. 2012;11:57\u201367.","journal-title":"Familial Cancer"},{"key":"7352_CR28","doi-asserted-by":"crossref","first-page":"149","DOI":"10.7314\/APJCP.2016.17.S3.149","volume":"17","author":"VR Yassaee","year":"2016","unstructured":"Yassaee VR, Ravesh Z, Soltani Z, Hashemi-Gorji F, Poorhosseini SM, Anbiaee R, et al. Mutation spectra of BRCA genes in Iranian women with early onset breast Cancer - 15 years experience. Asian Pac J Cancer Prev. 2016;17:149\u201353.","journal-title":"Asian Pac J Cancer Prev"},{"key":"7352_CR29","first-page":"274","volume":"9","author":"H Khalil","year":"2018","unstructured":"Khalil H, Monem F, Al-Quobaili F. Identification of three BRCA1\/2 mutations and a study of the likelihood of an association with certain characteristics in Syrian familial breast Cancer patients. Middle East J Cancer. 2018;9:274\u201381.","journal-title":"Middle East J Cancer"},{"key":"7352_CR30","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1002\/ijc.30771","volume":"141","author":"S Lolas Hamameh","year":"2017","unstructured":"Lolas Hamameh S, Renbaum P, Kamal L, Dweik D, Salahat M, Jaraysa T, et al. Genomic analysis of inherited breast cancer among Palestinian women: genetic heterogeneity and a founder mutation in TP53. Int J Cancer. 2017;141:750\u20136.","journal-title":"Int J Cancer"},{"key":"7352_CR31","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1007\/s10549-017-4635-4","volume":"168","author":"A-J Alhuqail","year":"2018","unstructured":"Alhuqail A-J, Alzahrani A, Almubarak H, Al-Qadheeb S, Alghofaili L, Almoghrabi N, et al. High prevalence of deleterious BRCA1 and BRCA2 germline mutations in Arab breast and ovarian cancer patients. Breast Cancer Res Treat. 2018;168:695\u2013702.","journal-title":"Breast Cancer Res Treat"},{"key":"7352_CR32","first-page":"JGO","volume":"4","author":"O Abulkhair","year":"2018","unstructured":"Abulkhair O, Al Balwi M, Makram O, Alsubaie L, Faris M, Shehata H, et al. Prevalence of BRCA1 and BRCA2 mutations among high-risk Saudi patients with breast cancer. J Glob Oncol. 2018;4:JGO\u201318.","journal-title":"J Glob Oncol"},{"key":"7352_CR33","doi-asserted-by":"crossref","first-page":"8297","DOI":"10.1158\/0008-5472.CAN-06-0503","volume":"66","author":"KE Malone","year":"2006","unstructured":"Malone KE, Daling JR, Doody DR, Hsu L, Bernstein L, Coates RJ, et al. Prevalence and predictors of BRCA1 and BRCA2 mutations in a population-based study of breast Cancer in white and black American women ages 35 to 64 years. Cancer Res. 2006;66:8297\u2013308.","journal-title":"Cancer Res"},{"key":"7352_CR34","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1200\/JCO.2010.33.0068","volume":"30","author":"PJ Goodwin","year":"2012","unstructured":"Goodwin PJ, Phillips K-A, West DW, Ennis M, Hopper JL, John EM, et al. Breast cancer prognosis in BRCA1 and BRCA2 mutation carriers: an international prospective breast Cancer family registry population-based cohort study. J Clin Oncol Off J Am Soc Clin Oncol. 2012;30:19\u201326.","journal-title":"J Clin Oncol Off J Am Soc Clin Oncol"},{"key":"7352_CR35","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.3892\/ijo.2012.1595","volume":"41","author":"S Novakovi\u0107","year":"2012","unstructured":"Novakovi\u0107 S, Milatovi\u0107 M, Cerkovnik P, Stegel V, Krajc M, Ho\u010dEvar M, et al. Novel BRCA1 and BRCA2 pathogenic mutations in Slovene hereditary breast and ovarian cancer families. Int J Oncol. 2012;41:1619\u201327.","journal-title":"Int J Oncol"},{"key":"7352_CR36","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/cge.12119","volume":"85","author":"M Krajc","year":"2014","unstructured":"Krajc M, Zadnik V, Novakovi\u0107 S, Stegel V, Teugels E, Be\u0161i\u010d N, et al. Geographical distribution of Slovenian BRCA1\/2 families according to family origin: implications for genetic screening: geographical distribution of Slovenian BRCA1\/2 families. Clin Genet. 2014;85:59\u201363.","journal-title":"Clin Genet"},{"key":"7352_CR37","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/1471-2350-12-9","volume":"12","author":"V Stegel","year":"2011","unstructured":"Stegel V, Krajc M, \u017dgajnar J, Teugels E, De Gr\u00e8ve J, Ho\u010devar M, et al. The occurrence of germline BRCA1 and BRCA2sequence alterations in Slovenian population. BMC Med Genet. 2011;12:9.","journal-title":"BMC Med Genet."},{"key":"7352_CR38","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s12881-016-0274-6","volume":"17","author":"G Cini","year":"2016","unstructured":"Cini G, Mezzavilla M, Della Puppa L, Cupelli E, Fornasin A, D\u2019Elia AV, et al. Tracking of the origin of recurrent mutations of the BRCA1 and BRCA2 genes in the north-east of Italy and improved mutation analysis strategy. BMC Med Genet. 2016;17:11.","journal-title":"BMC Med Genet"},{"key":"7352_CR39","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1093\/pcmedi\/pby010","volume":"1","author":"A Sharma-Oates","year":"2018","unstructured":"Sharma-Oates A, Shaaban AM, Tomlinson I, Wynne L, Cazier J-B, Sundar S. Heterogeneity of germline variants in high risk breast and ovarian cancer susceptibility genes in India. Precis Clin Med. 2018;1:75\u201387.","journal-title":"Precis Clin Med"},{"key":"7352_CR40","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1038\/onc.2011.271","volume":"31","author":"Z Kais","year":"2012","unstructured":"Kais Z, Chiba N, Ishioka C, Parvin JD. Functional differences among BRCA1 missense mutations in the control of centrosome duplication. Oncogene. 2012;31:799.","journal-title":"Oncogene"},{"key":"7352_CR41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3233\/BD-130348","volume":"34","author":"F Cherbal","year":"2013","unstructured":"Cherbal F, Bakour R, Adane S, Boualga K. BRCA1 and BRCA2 germline mutation spectrum in hereditary breast\/ovarian cancer families from Maghrebian countries. Breast Dis. 2013;34:1\u20138.","journal-title":"Breast Dis"},{"key":"7352_CR42","first-page":"971","volume":"14","author":"V Laplace-Marieze","year":"1999","unstructured":"Laplace-Marieze V, Presneau N, Sylvain V, Kwiatkowski F, Lortholary A, Hardouin A, et al. Systematic sequencing of the BRCA-1 coding region for germ-line mutation detection in 70 French high-risk families. Int J Oncol. 1999;14:971\u20138.","journal-title":"Int J Oncol"},{"key":"7352_CR43","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1136\/jmg.2006.044388","volume":"44","author":"J Simard","year":"2006","unstructured":"Simard J, Dumont M, Moisan A-M, Gaborieau V, Vezina H, Durocher F, et al. Evaluation of BRCA1 and BRCA2 mutation prevalence, risk prediction models and a multistep testing approach in French-Canadian families with high risk of breast and ovarian cancer. J Med Genet. 2006;44:107\u201321.","journal-title":"J Med Genet"},{"key":"7352_CR44","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1007\/s10689-010-9372-3","volume":"9","author":"L Cavallone","year":"2010","unstructured":"Cavallone L, Arcand SL, Maugard CM, Nolet S, Gaboury LA, Mes-Masson A-M, et al. Comprehensive BRCA1 and BRCA2 mutation analyses and review of French Canadian families with at least three cases of breast cancer. Familial Cancer. 2010;9:507\u201317.","journal-title":"Familial Cancer"},{"key":"7352_CR45","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1038\/ejhg.2014.16","volume":"22","author":"L Cast\u00e9ra","year":"2014","unstructured":"Cast\u00e9ra L, Krieger S, Rousselin A, Legros A, Baumann J-J, Bruet O, et al. Next-generation sequencing for the diagnosis of hereditary breast and ovarian cancer using genomic capture targeting multiple candidate genes. Eur J Hum Genet. 2014;22:1305\u201313.","journal-title":"Eur J Hum Genet"},{"issue":"8","key":"7352_CR46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13048-015-0124-8","volume":"2015","author":"MH Belanger","year":"2015","unstructured":"Belanger MH, Dolman L, Arcand SL, Shen Z, Chong G, Mes-Masson A-M, et al. A targeted analysis identifies a high frequency of BRCA1 and BRCA2 mutation carriers in women with ovarian cancer from a founder population. J Ovarian Res. 2015;2015(8):1.","journal-title":"J Ovarian Res"},{"key":"7352_CR47","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1007\/s12253-017-0242-2","volume":"24","author":"H Gaceb","year":"2018","unstructured":"Gaceb H, Cherbal F, Bakour R, Ould-Rouis A, Mahfouf H. Clinicopathological and molecular study of triple-negative breast Cancer in Algerian patients. Pathol Oncol Res. 2018;24:297\u2013308.","journal-title":"Pathol Oncol Res"},{"key":"7352_CR48","doi-asserted-by":"crossref","first-page":"2869","DOI":"10.1001\/jama.298.24.2869","volume":"298","author":"EM John","year":"2007","unstructured":"John EM, Miron A, Gong G, Phipps AI, Felberg A, Li FP, et al. Prevalence of pathogenic BRCA1 mutation carriers in 5 US racial\/ethnic groups. Jama. 2007;298:2869\u201376.","journal-title":"Jama."},{"key":"7352_CR49","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1007\/s10549-008-0190-3","volume":"117","author":"L Papi","year":"2009","unstructured":"Papi L, Putignano AL, Congregati C, Zanna I, Sera F, Morrone D, et al. Founder mutations account for the majority of BRCA1-attributable hereditary breast\/ovarian cancer cases in a population from Tuscany, Central Italy. Breast Cancer Res Treat. 2009;117:497\u2013504.","journal-title":"Breast Cancer Res Treat"},{"key":"7352_CR50","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1002\/humu.21414","volume":"32","author":"V Caux-Moncoutier","year":"2011","unstructured":"Caux-Moncoutier V, Cast\u00e9ra L, Tirapo C, Michaux D, R\u00e9mon M-A, Laug\u00e9 A, et al. EMMA, a cost- and time-effective diagnostic method for simultaneous detection of point mutations and large-scale genomic rearrangements: application to BRCA1 and BRCA2 in 1,525 patients. Hum Mutat. 2011;32:325\u201334.","journal-title":"Hum Mutat"},{"key":"7352_CR51","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/s10549-015-3377-4","volume":"151","author":"E Kang","year":"2015","unstructured":"Korean Hereditary Breast Cancer Study Group, Kang E, Seong M-W, Park SK, Lee JW, Lee J, et al. The prevalence and spectrum of BRCA1 and BRCA2 mutations in Korean population: recent update of the Korean hereditary breast Cancer (KOHBRA) study. Breast Cancer Res Treat. 2015;151:157\u201368.","journal-title":"Breast Cancer Res Treat"},{"key":"7352_CR52","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1007\/s10038-006-0404-7","volume":"51","author":"M Infante","year":"2006","unstructured":"Infante M, Dur\u00e1n M, Esteban-Carde\u00f1osa E, Miner C, Velasco E. High proportion of novel mutations of BRCA1 and BRCA2 in breast\/ovarian cancer patients from Castilla-Le\u00f3n (Central Spain). J Hum Genet. 2006;51:611\u20137.","journal-title":"J Hum Genet"},{"key":"7352_CR53","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1007\/s10549-009-0661-1","volume":"122","author":"M Infante","year":"2010","unstructured":"Infante M, Dur\u00e1n M, Lasa A, Acedo A, de la Hoya M, Esteban-Carde\u00f1osa E, et al. Two founder BRCA2 mutations predispose to breast cancer in young women. Breast Cancer Res Treat. 2010;122:567\u201371.","journal-title":"Breast Cancer Res Treat"},{"key":"7352_CR54","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1186\/1471-2407-13-243","volume":"13","author":"P Blay","year":"2013","unstructured":"Blay P, Santamar\u00eda I, Pitiot AS, Luque M, Alvarado MG, Lastra A, et al. Mutational analysis of BRCA1 and BRCA2 in hereditary breast and ovarian cancer families from Asturias (northern Spain). BMC Cancer. 2013;13:243.","journal-title":"BMC Cancer"},{"key":"7352_CR55","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1007\/s10689-015-9814-z","volume":"14","author":"I de Juan","year":"2015","unstructured":"de Juan I, Palanca S, Domenech A, Feliubadal\u00f3 L, Segura \u00c1, Osorio A, et al. BRCA1 and BRCA2 mutations in males with familial breast and ovarian cancer syndrome. Results of a Spanish multicenter study. Familial Cancer. 2015;14:505\u201313.","journal-title":"Familial Cancer"},{"key":"7352_CR56","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1007\/s10549-012-2159-5","volume":"134","author":"H Kim","year":"2012","unstructured":"Korean Breast Cancer Study Group, Kim H, Cho D-Y, Choi DH, Choi S-Y, Shin I, et al. Characteristics and spectrum of BRCA1 and BRCA2 mutations in 3,922 Korean patients with breast and ovarian cancer. Breast Cancer Res Treat. 2012;134:1315\u201326.","journal-title":"Breast Cancer Res Treat"},{"issue":"10","key":"7352_CR57","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1093\/annonc\/mdz235","volume":"30","author":"HJ Burstein","year":"2019","unstructured":"Burstein HJ, Curigliano G, Loibl S, Dubsky P, Gnant M, Poortmans P, et al. Estimating the benefits of therapy for early-stage breast cancer: the St. Gallen international consensus guidelines for the primary therapy of early breast cancer 2019. Ann Oncol. 2019;30(10):1541\u201357.","journal-title":"Ann Oncol"},{"key":"7352_CR58","volume-title":"Genetic\/familial high-risk assessment: breast, ovarian and pancreatic. Version 1.2020-December 4","author":"National Comprehensive Cancer Network (NCCN) Clinical Practices Guidelines in Oncology","year":"2019","unstructured":"National Comprehensive Cancer Network (NCCN) Clinical Practices Guidelines in Oncology. Genetic\/familial high-risk assessment: breast, ovarian and pancreatic. Version 1.2020-December 4, 2019. http:\/\/www.nccn.org. Accessed 12 June 2020."}],"container-title":["BMC Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12885-020-07352-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12885-020-07352-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12885-020-07352-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T23:11:48Z","timestamp":1630969908000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmccancer.biomedcentral.com\/articles\/10.1186\/s12885-020-07352-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,7]]},"references-count":58,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["7352"],"URL":"https:\/\/doi.org\/10.1186\/s12885-020-07352-9","relation":{},"ISSN":["1471-2407"],"issn-type":[{"value":"1471-2407","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,7]]},"assertion":[{"value":"17 December 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 August 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 September 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The study was approved by the Ethics Committee for Biomedical Research of the Faculty of Medicine and Pharmacy of Rabat (CERB) registered under number IORG0006594. All participants gave a written informed consent to participate in the study.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All participants provided written informed consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"859"}}