Familial Cancer

, Volume 12, Issue 4, pp 767–777

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

  • Inmaculada de Juan Jiménez
  • Zaida García Casado
  • Sarai Palanca Suela
  • Eva Esteban Cardeñosa
  • José Antonio López Guerrero
  • Ángel Segura Huerta
  • Isabel Chirivella González
  • Ana Beatriz Sánchez Heras
  • Mª José Juan Fita
  • Isabel Tena García
  • Carmen Guillen Ponce
  • Eduardo Martínez de Dueñas
  • Ignacio Romero Noguera
  • Dolores Salas Trejo
  • Mercedes Goicoechea Sáez
  • Pascual Bolufer Gilabert
Short Communication

DOI: 10.1007/s10689-013-9622-2

Cite this article as:
de Juan Jiménez, I., García Casado, Z., Palanca Suela, S. et al. Familial Cancer (2013) 12: 767. doi:10.1007/s10689-013-9622-2

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.

Keywords

Hereditary breast and ovarian cancer (HBOC)BRCA1BRCA2Recurrent mutationsNovel mutationsRelationship genotype-phenotype

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Inmaculada de Juan Jiménez
    • 1
  • Zaida García Casado
    • 2
  • Sarai Palanca Suela
    • 1
  • Eva Esteban Cardeñosa
    • 1
  • José Antonio López Guerrero
    • 2
  • Ángel Segura Huerta
    • 3
  • Isabel Chirivella González
    • 4
  • Ana Beatriz Sánchez Heras
    • 5
  • Mª José Juan Fita
    • 6
  • Isabel Tena García
    • 7
  • Carmen Guillen Ponce
    • 5
  • Eduardo Martínez de Dueñas
    • 7
  • Ignacio Romero Noguera
    • 6
  • Dolores Salas Trejo
    • 8
  • Mercedes Goicoechea Sáez
    • 8
  • Pascual Bolufer Gilabert
    • 1
  1. 1.Laboratory of Molecular Biology, Service of Clinical Analysis, Escuela de Enfermería 7ªHospital Universitario La FeValenciaSpain
  2. 2.Laboratory of Molecular BiologyInstituto Valenciano de Oncologia (IVO)ValenciaSpain
  3. 3.Genetic Counseling UnitHospital La FeValenciaSpain
  4. 4.Genetic Counseling UnitClinic HospitalValenciaSpain
  5. 5.Genetic Counseling UnitHospital de ElcheAlicanteSpain
  6. 6.Genetic Counseling UnitInstituto Valenciano de Oncologia (IVO)ValenciaSpain
  7. 7.Genetic Counseling UnitHospital General de CastellónCastellónSpain
  8. 8.Department of Public HealthCancer Plan Office, Conselleria de SanitatValenciaSpain