BRCA1 5272-1G>A and BRCA2 5374delTATG are founder mutations of high relevance for genetic counselling in breast/ovarian cancer families of Spanish origin |
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Authors: | M Infante,M Durá n,A Acedo,L Pé rez-Cabornero,DJ Sanz,M Garcí a-Gonzá lez,E Beristain,E Esteban-Cardeñ osa,M de la Hoya,A Teulé ,A Vega,M-I Tejada,E Lastra,C Miner, EA Velasco |
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Affiliation: | Grupo de Genética del Cáncer, Instituto de Biología y Genética Molecular (UVa-CSIC), Valladolid;, Servicio de Oncología, Hospital General Yagüe, Burgos;, Laboratorio de Genética Molecular (Departamento de Bioquímica). Hospital de Cruces. Barakaldo;, Laboratorio de Biología Molecular, Servicio de Biopatología Clínica, Hospital Universitario La Fe, Valencia;, Laboratorio de Oncología Molecular, Hospital Clínico San Carlos, Madrid;, Red Temática de Investigación Cooperativa (RD06/0020/0021), Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Science and Innovation, Madrid;, Programa de Consejo Genético en Cáncer, Instituto Catalán de Oncología, ICO-L'Hospitalet;, and Fundación Pública Galega de Medicina Xenómica (FPGMX-SERGAS), CIBERER, Santiago de Compostela, Spain |
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Abstract: | Infante M, Durán M, Acedo A, Pérez-Cabornero L, Sanz DJ, García-González M, Beristain E, Esteban-Cardeñosa E, de la Hoya M, Teulé A, Vega A, Tejada M-I, Lastra E, Miner C, Velasco EA. BRCA1 5272-1G>A and BRCA2 5374delTATG are founder mutations of high relevance for genetic counselling in breast/ovarian cancer families of Spanish origin. The distribution of BRCA1 and BRCA2 germ line mutations in breast/ovarian cancer families varies among different populations, which typically present a wide spectrum of unique mutations. Splicing mutation 5272-1G>A of BRCA1 and frameshift mutation 5374delTATG of BRCA2 are highly prevalent mutations in Castilla-León (Spain), accounting for 18.4% and 13.6% of BRCA1 and BRCA2 positive families, respectively. To test the presence of founder effects, 9 Spanish 5272-1G>A and 13 5374delTATG families were genotyped with polymorphic markers linked to BRCA1 or BRCA2 . All the 5272-1G>A families shared a common haplotype in eight markers (1.1 Mb region) and the mutation age was estimated in 15 generations (∼380 years). A conserved haplotype associated to 5374delTATG was observed in four markers (0.82 Mb). The mutation occurred approximately 48 generations ago (∼1200 years). Each mutation likely arose from a common ancestor that could be traced to a small area of Castilla-León and expanded to other Spanish regions. They can have a significant impact on the clinical management of asymptomatic carriers as well as on the genetic screening strategy to be followed in populations with Spanish ancestries. |
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Keywords: | BRCA1 BRCA2 breast cancer founder mutations ovarian cancer |
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