RT info:eu-repo/semantics/article
T1 The highly prevalent BRCA2 mutation c.2808_2811del (3036delACAA) is located in a mutational hotspot and has multiple origins
A1 Infante Sanz, María Del Mar
A1 Duran Dominguez, María Mercedes
A1 Acedo, Alberto
A1 Sánchez Tapia, Eva María
A1 Díez Gómez, Beatríz
A1 Barroso, Alicia
A1 García González, María
A1 Feliubadalo, L.
A1 Lasa, Adriana
A1 Hoya, Miguel de la
A1 Esteban Cardeñosa, Eva
A1 Diez, Orland
A1 Martinez Bouzas, Cristina
A1 Godino, Javier
A1 Teulé, Alexandra
A1 Osorio, Ana
A1 Lastra, Enrique
A1 González Sarmiento, Rogelio
A1 Miner, Cristina
A1 Velasco, Eladio A.
AB BRCA2-c.2808_2811del (3036delACAA) is one of the most reportedgerm line mutations in non-Ashkenazi breast cancer patients. Weinvestigated its genetic origin in 51 Spanish carrier families thatwere genotyped with 11 13q polymorphic markers. Three independentassociated haplotypes were clearly distinguished accounting for23 [west Castilla y León (WCL)], 20 [east Castilla y León (ECL)]and 6 (South of Spain) families. Mutation age was estimated withthe Disequilibrium Mapping using Likelihood Estimation softwarein a range of 45–68 and 45–71 generations for WCL and ECL haplotypes,respectively. The most prevalent variants, c.2808_2811deland c.2803G > A, were located in a double-hairpin loop structure(c.2794–c.2825) predicted by Quikfold that was proposed as a mutationalhotspot. To check this hypothesis, random mutagenesis wasperformed over a 923 bp fragment of BRCA2, and 86 DNA variantswere characterized. Interestingly, three mutations reported in themutation databases (c.2680G > A, c.2944del and c.2957dup) werereplicated and 20 affected the same position with different nucleotidechanges. Moreover, five variants were placed in the same hairpin loopof c.2808_2811del, and one affected the same position (c.2808A > G).In conclusion, our results support that at least three different mutationalevents occurred to generate c.2808_2811del. Other highlyprevalent DNA variants, such as BRCA1-c.68_69delAG, BRCA2-c.5946delT and c.8537delAG, are concentrated in hairpin loops, suggestingthat these structures may represent mutational hotspots.
PB Oxford University Press
SN 0143-3334
YR 2013
FD 2013
LK https://uvadoc.uva.es/handle/10324/64454
UL https://uvadoc.uva.es/handle/10324/64454
LA eng
NO Carcinogenesis, 34 (11), pp. 2505-2511.
DS UVaDOC
RD 19-jul-2025