Abstract
Various studies have been published in Italy regarding the different BRCA1 mutations, but only the BRCA1-5083del19 mutation is recurrent and specific to individuals of Italian descent with a founder effect on the Calabrian population. In our previous study, BRCA1-5083del19 mutation carriers were found in four index cases of 106 Sicilian patients selected for familial and/or hereditary breast/ovarian cancers. The high frequency rate of this mutation identified in the Sicilian population led us to perform haplotype analysis in all family carriers. Five highly polymorphic microsatellite markers were used (D17S1320, D17S932, D17S1323, D17S1326, D17S1325) to establish whether or not all these families had a common ancestor. This analysis showed that all mutation carriers of these families had a common allele. None of the non-carriers of the mutation or of the 50 healthy Sicilian controls showed this haplotype. This allelotype analysis highlighted the presence of a common allele (ancestor), thus suggesting the presence of a founder effect in the Sicilian population. Our results are in contrast with other studies but only the allelotype analysis of all the BRCA1-5083del19 mutation carriers of two neighboring regions of the south of Italy (Calabria and Sicily) will make it possible to identify the real ancestor of this mutation.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Miki Y, Swensen J, Shattuck-Eidens D et al (1994) A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 266:66–71
Ford D, Easton DF, Stratton M, Breast Cancer linkage Consortium et al (1998) Genetic heterogenicity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. Am J Hum Genet 62:676–689
Pharoah PD, Antoniou A, Bobrow M et al (2002) Polygenic susceptibility to breast cancer and implications for prevention. Nat Genet 31:33–36
Antoniou AC, Pharoah PD, Narod S et al (2005) Breast and ovarian cancer risks to carriers of the BRCA1 5382insC and 185delAG and BRCA2 6174delT mutations: a combined analysis of 22 population based studies. J Med Genet 42:602–603
Rudkin TM, Hamel N, Galvez M et al (2006) The frequent BRCA1 mutation 1135insA has multiple origins: a haplotype study in different populations. BMC Med Genet 7:15
Ferla R, Calo V, Cascio S et al (2007) Founder mutations in BRCA1 and BRCA2 genes. Ann Oncol 18(Supp 6):vi93–vi98
Struewing JP, Abeliovich D, Peretz T et al (1995) The carrier frequency of the BRCA1 185delAG mutation is approximately 1 percent in Ashkenazi Jewish individuals. Nat Genet 11:198–200
Roa BB, Boyd AA, Volcik K et al (1996) Ashkenazi Jewish population frequencies for common mutations in BRCA1 and BRCA2. Nat Genet 14:185–187
Simard J, Tonin P, Durocher F et al (1994) Common origins of BRCA1 mutations in Canadian breast and ovarian cancer families. Nat Genet 8:392–398
Vehmanen P, Friedman LS, Eerola H et al (1997) Low proportion of BRCA1 and BRCA2 mutations in Finnish breast cancer families: evidence for additional susceptibility genes. Hum Mol Genet 6:2309–2315
Johansson O, Ostermeyer EA, Hakansson S et al (1996) Founding BRCA1 mutations in hereditary breast and ovarian cancer in Southern Sweden. Am J Hum Genet 58:441–450
Hakansson O, Johansson U, Sellberg G et al (1997) Moderate frequency of BRCA1 and BRCA2 germ-line mutations in Scandinavian familial breast cancer. Am J Hum Genet 60:1068–1078
Peelen T, van der Vliet M, Petrij-Bosch A et al (1997) A high proportion of novel mutations in BRCA1 with strong founder effects among Dutch and Belgian hereditary breast and ovarian cancer families. Am J Hum Genet 60:1041–1049
Thorlacius S, Olafsdottir G, Tryggvadottir L et al (1996) A single BRCA2 mutation in male and female breast cancer families from Iceland with varied cancer phenotypes. Nat Genet 13:117–119
Baudi F, Quaresima B, Grandinetti C et al (2001) Evidence of a founder mutation of BRCA1 gene in a highly homogeneous population from southern Italy with breast/ovarian cancer. Hum Mutat 18:163–164
Nedelcu R, Liede A, Aube J et al (2002) BRCA mutations in Italian breast/ovarian cancer Families. Eur J Hum Genet 10:150–152
Ottini L, D’Amico C, Noviello C et al (2000) BRCA1 and BRCA2 mutations in central and southern Italian patients. Breast Cancer Res 2:307–310
Russo A, Calo` V, Agnese V et al (2006) BRCA1 genetic testing in 106 breast and ovarian cancer families from southern Italy (Sicily): a mutation analyses. Breast Cancer Res Treat (2007 Jan 13)
National center for biotechnology information (NCBI) Data Base. Retrived online (http://www.ncbi.nlm.nih.gov)
Cipollini G, Tommasi S, Paradiso A et al (2004) Genetic alterations in hereditary breast cancer. Ann Oncol 15(Supp 1):i7–i13
Author information
Authors and Affiliations
Corresponding author
Additional information
Antonio Russo and Valentina Calò have contributed equally to this work.
Rights and permissions
About this article
Cite this article
Russo, A., Calò, V., Bruno, L. et al. Is BRCA1-5083del19, identified in breast cancer patients of Sicilian origin, a Calabrian founder mutation?. Breast Cancer Res Treat 113, 67–70 (2009). https://doi.org/10.1007/s10549-008-9906-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10549-008-9906-7