title: Novel and recurrent BRCA1/BRCA2 mutations in early onset and familial breast and ovarian cancer detected in the Program of Genetic Counseling in Cancer of Valencian Community (eastern Spain). Relationship of family phenotypes with mutation prevalence.
abstract: During the first 6 years of the Program of Genetic Counselling in Cancer of Valencia (eastern Spain), 310 mutations (155 in BRCA1 and 155 in BRCA2) in 1,763 hereditary breast (BC) and ovarian cancer (OC) families were identified. Of the mutations found 105 were distinct (53 in BRCA1 and 52 in BRCA2), eight new and 37 recurrent. Two of the novel mutations were frame-shift placed in exons 2 and 11 of BRCA1 and the remaining six were placed in BRCA2; four frame-shift (three in exon 11 and one in exon 23), one deletion of the entire exon 19 and one in the intervening sequence of exon 22. The BRCA1 mutations with higher recurrence were c.66_68delAG, c.5123C > A, c.1961delA, c.3770_3771delAG and c.5152+5G > A that covered 45.2% of mutations of this gene. The age of onset of BCs of c.68_69delAG mutation carriers occurs later than for the other recurrent mutations of this gene (45 vs. 37 years; p = 0.008). The BRCA2 mutations with higher recurrence were c.9026_9030delATCAT, c.3264insT and c.8978_8991del14 which represented 43.2% of all mutations in this gene, being the most recurrent mutation by far c.9026_9030delATCAT that represents 21.3% of BRCA2 mutations and 10.6% of all mutations. Probands with family histories of BC and OC, or OC and/or BC in at least two first degree relatives, were the more likely to have BRCA1/BRCA2 mutations (35.2% of the total mutations). And that most BRCA1mutations (73.19% mutations) occurred in probands with early-onset BC or with family history of OC.
authors.affiliation: Laboratory of Molecular Biology, Service of Clinical Analysis, Escuela de Enfermería 7ª, Hospital Universitario La Fe, Avd. Campanar 21, 46009, Valencia, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: de Juan Jiménez
authors.forename: Zaida
authors.initials: Z
authors.lastname: García Casado
authors.forename: Sarai
authors.initials: S
authors.lastname: Palanca Suela
authors.forename: Eva
authors.initials: E
authors.lastname: Esteban Cardeñosa
authors.forename: José Antonio
authors.initials: JA
authors.lastname: López Guerrero
authors.forename: Ángel
authors.initials: Á
authors.lastname: Segura Huerta
authors.forename: Isabel
authors.initials: I
authors.lastname: Chirivella González
authors.forename: Ana Beatriz
authors.initials: AB
authors.lastname: Sánchez Heras
authors.forename: Ma José
authors.initials: MJ
authors.lastname: Juan Fita
authors.forename: Isabel
authors.initials: I
authors.lastname: Tena García
authors.forename: Carmen
authors.initials: C
authors.lastname: Guillen Ponce
authors.forename: Eduardo
authors.initials: E
authors.lastname: Martínez de Dueñas
authors.forename: Ignacio
authors.initials: I
authors.lastname: Romero Noguera
authors.forename: Dolores
authors.initials: D
authors.lastname: Salas Trejo
authors.forename: Mercedes
authors.initials: M
authors.lastname: Goicoechea Sáez
authors.forename: Pascual
authors.initials: P
authors.lastname: Bolufer Gilabert
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D055088:Early Detection of Cancer; D005190:Family; D005260:Female; D005500:Follow-Up Studies; D005817:Genetic Counseling; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D015995:Prevalence; D011379:Prognosis; D013030:Spain / Q000453:epidemiology; D055815:Young Adult
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D004273:DNA, Neoplasm