Twenty-three novel BRCA1 and BRCA2 sequence alterations in breast and/or ovarian cancer families of Eastern Spain.
It is well established that mutations in BRCA1 and BRCA2 genes significantly increase the risk of breast and ovarian cancer. We here report 23 novel genetic variants of the BRCA1 and BRCA2 genes found in 349 cancer-prone unrelated families from Eastern Spain detected during the first 2 years of performance of the Program of Genetic Counseling of Valencia Community. Mutational screening was performed by pre-screening the heteroduplex formed in the PCR products obtained amplifying BRCA1 and BRCA2 genes by conformation sensitive electrophoresis. We detected 10 deletereous mutations, four in BRCA1 (three frame-shift (FS) and one nonsense mutation (NS)) and six in BRCA2 (four FS and one NS mutation). Moreover, we detected 13 unclassified variants, four in BRCA1 (one missense (MS), two synonymous (SYN) and one intronic (I) variant) and nine in BRCA2 (six MS, one SYN and two I). The relevance of the novel mutations is discussed. Our contribution broadens the BRCA1/2 world mutational spectra.
Esteban Cardeñosa
Eva
E
Laboratorio de Biología Molecular, Servicio de Biopatología Clínica, Escuela de Enfermería 7a planta, Hospital Universitario La Fe, Avd. Campanar 21, 46009, Valencia, Spain.
Bolufer Gilabert
Pascual
P
Palanca Suela
Sarai
S
Oltra Soler
Silvestre
S
Barragán González
Eva
E
Velasco Sampedro
Eladio
E
Chirivella González
Isabel
I
Segura Huerta
Angel
A
Guillén Ponce
Carmen
C
Martínez de Dueñas
Eduardo
E
D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D005190:Family; D005260:Female; D005820:Genetic Testing; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics*; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion; D013030:Spain / Q000453:epidemiology
D019313:BRCA1 Protein; D024682:BRCA2 Protein; D004273:DNA, Neoplasm