title: Hereditary breast cancer in Middle Eastern and North African (MENA) populations: identification of novel, recurrent and founder BRCA1 mutations in the Tunisian population.
abstract: Germ-line mutations in BRCA1 breast cancer susceptibility gene account for a large proportion of hereditary breast cancer families and show considerable ethnic and geographical variations. The contribution of BRCA1 mutations to hereditary breast cancer has not yet been thoroughly investigated in Middle Eastern and North African populations. In this study, 16 Tunisian high-risk breast cancer families were screened for germline mutations in the entire BRCA1 coding region and exon-intron boundaries using direct sequencing. Six families were found to carry BRCA1 mutations with a prevalence of 37.5%. Four different deleterious mutations were detected. Three truncating mutations were previously described: c.798_799delTT (916 delTT), c.3331_3334delCAAG (3450 delCAAG), c.5266dupC (5382 insC) and one splice site mutation which seems to be specific to the Tunisian population: c.212 + 2insG (IVS5 + 2insG). We also identified 15 variants of unknown clinical significance. The c.798_799delTT mutation occurred at an 18% frequency and was shared by three apparently unrelated families. Analyzing five microsatellite markers in and flanking the BRCA1 locus showed a common haplotype associated with this mutation. This suggests that the c.798_799delTT mutation is a Tunisian founder mutation. Our findings indicate that the Tunisian population has a spectrum of prevalent BRCA1 mutations, some of which appear as recurrent and founding mutations.
authors: Department of Molecular Immuno-Oncology, Faculty of Medicine, 5019 Monastir, Tunisia.
authors: Wijden
authors: W
authors: Mahfoudh
authors: Noureddine
authors: N
authors: Bouaouina
authors: Slim Ben
authors: SB
authors: Ahmed
authors: Sallouha
authors: S
authors: Gabbouj
authors: Jingxuan
authors: J
authors: Shan
authors: Rebecca
authors: R
authors: Mathew
authors: Nancy
authors: N
authors: Uhrhammer
authors: Yves-Jean
authors: YJ
authors: Bignon
authors: Wafa
authors: W
authors: Troudi
authors: Amel Ben Ammar
authors: AB
authors: Elgaaied
authors: Elham
authors: E
authors: Hassen
authors: Lotfi
authors: L
authors: Chouchane
references: J Clin Oncol. 2004 Feb 15;22(4):735-42
references: 14966099
references: Fam Cancer. 2006;5(4):379-87
references: 16826315
references: Int J Med Sci. 2008 Jul 08;5(4):197-202
references: 18645608
references: Saudi Med J. 2002 Jun;23(6):700-4
references: 12070551
references: Cancer Biomark. 2008;4(1):11-8
references: 18334730
references: Breast Cancer Res Treat. 2008 Nov;112(2):353-8
references: 18176857
references: Mod Pathol. 2005 Jul;18(7):891-7
references: 15803183
references: Sante Publique. 2002 Sep;14(3):231-41
references: 12564048
references: East Mediterr Health J. 2003 May;9(3):448-63
references: 15751939
references: Am J Hum Genet. 1996 Feb;58(2):271-80
references: 8571953
references: BMC Med Genet. 2006 Mar 01;7:15
references: 16509964
references: Int J Surg. 2007 Aug;5(4):225-33
references: 17660128
references: Mol Biol Rep. 2011 Jan;38(1):343-8
references: 20358297
references: JAMA. 2008 Jan 9;299(2):194-201
references: 18182601
references: Breast Cancer Res Treat. 2008 Jul;110(1):99-109
references: 17851763
references: Breast Cancer Res Treat. 2007 Jun;103(2):219-24
references: 17039264
references: Cancer Genet Cytogenet. 2008 Jul;184(1):62-6
references: 18558292
references: Hum Mutat. 2000 Apr;15(4):381-2
references: 10737987
references: Nat Genet. 2002 May;31(1):33-6
references: 11984562
references: Cancer Epidemiol Biomarkers Prev. 2001 May;10(5):467-73
references: 11352856
references: Nucleic Acids Res. 1988 Feb 11;16(3):1215
references: 3344216
references: Tunis Med. 2002 Sep;80(9):515-8
references: 12632763
references: BMC Cancer. 2009 Jul 20;9:245
references: 19619314
references: J Med Genet. 2005 Jul;42(7):602-3
references: 15994883
references: Fam Cancer. 2004;3(1):15-20
references: 15131401
references: Am J Hum Genet. 1997 May;60(5):1059-67
references: 9150153
references: Breast Cancer Res Treat. 2007 Nov;105(3):267-76
references: 17221156
references: Breast Cancer Res Treat. 2007 Jun;103(2):225-32
references: 17080309
references: Hum Mol Genet. 1997 Feb;6(2):285-9
references: 9063749
references: Mutat Res. 2005 Oct 15;578(1-2):395-405
references: 16026807
references: Breast Cancer Res Treat. 2009 Jul;116(2):379-86
references: 18704680
references: Proc Natl Acad Sci U S A. 2006 Mar 7;103(10):3770-4
references: 16537453
references: Saudi Med J. 2004 Sep;25(9):1245-8
references: 15448776
references: J Hum Genet. 2007;52(11):915-920
references: 17922257
references: Nature. 1995 Dec 21-28;378(6559):789-92
references: 8524414
references: Cancer Genet Cytogenet. 2006 Apr 1;166(1):36-45
references: 16616110
references: Bull Cancer. 1999 Mar;86(3):302-6
references: 10210765
references: Eur J Cancer. 2006 Jul;42(10):1380-4
references: 16737811
references: Hum Mol Genet. 1995;4 Spec No:1811-7
references: 8541881
references: Ann Oncol. 2006 Jun;17 Suppl 7:vii30-3
references: 16760288
references: Saudi Med J. 2004 Jan;25(1):60-3
references: 14758382
references: Cancer Genomics Proteomics. 2008 Sep-Oct;5(5):253-61
references: 19129556
references: Ann Saudi Med. 2006 Jul-Aug;26(4):272-7
references: 16883082
references: CA Cancer J Clin. 2005 Mar-Apr;55(2):74-108
references: 15761078
references: J Med Genet. 2007 Jul;44(7):467-71
references: 17307836
references: Arch Inst Pasteur Tunis. 2000;77(1-4):11-5
references: 14658222
references: Bull Cancer. 2008 Feb;95(2):E5-9
references: 18304901
references: Tunis Med. 2003 Sep;81(9):696-701
references: 17722781
references: Int J Cancer. 2004 Jul 10;110(5):683-6
references: 15146557
references: Science. 1994 Oct 7;266(5182):66-71
references: 7545954
references: Gynecol Oncol. 1999 Mar;72(3):402-6
references: 10053113
references: J Natl Cancer Inst. 2006 Dec 6;98(23):1694-706
references: 17148771
references: Genet Med. 2005 Jan;7(1):34-9
references: 15654226
references: Oncologist. 2005 Aug;10(7):471-9
references: 16079314
references: Nat Rev Cancer. 2004 Sep;4(9):665-76
references: 15343273
references: Breast Cancer Res Treat. 2008 Feb;107(3):431-41
references: 17453335
references: J Natl Cancer Inst. 2002 Sep 18;94(18):1365-72
references: 12237282
references: Science. 2003 Oct 24;302(5645):643-6
references: 14576434
references: Am J Hum Genet. 1998 Mar;62(3):676-89
references: 9497246
references: Asian Pac J Cancer Prev. 2008 Jan-Mar;9(1):19-24
references: 18439066
references: Am J Hum Genet. 1997 May;60(5):1013-20
references: 9150148
references: Am J Hum Genet. 2003 May;72(5):1117-30
references: 12677558