BRCA1 5272-1G>A and BRCA2 5374delTATG are founder mutations of high relevance for genetic counselling in breast/ovarian cancer families of Spanish origin

Clinical Genetics
Mar InfanteEladio A Velasco

Abstract

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 (approximately 380 years). A conserved haplotype associated to 5374delTATG was observed in four markers (0.82 Mb). The mutation occurred approximately 48 generations ago (approximately 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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Citations

Sep 23, 2010·Breast Cancer Research and Treatment·Patricio Gonzalez-HormazabalLilian Jara
May 29, 2012·Breast Cancer Research : BCR·Alberto AcedoEladio A Velasco
Dec 2, 2009·Breast Cancer Research and Treatment·Mar InfanteEladio A Velasco
Dec 17, 2009·The European Journal of Health Economics : HEPAC : Health Economics in Prevention and Care·Julio Lopez-BastidaEnrique Quintero-Carrión
Nov 10, 2010·Oncology Nursing Forum·Cheryl B Crotser, Suzanne S Dickerson
Feb 6, 2020·International Journal of Cancer. Journal International Du Cancer·Paraskevi ApostolouEmmanouil Saloustros
Mar 11, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·David J SanzEladio A Velasco

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