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Breast Cancer Research and Treatment

, Volume 132, Issue 1, pp 307–315 | Cite as

Detection of a large rearrangement in PALB2 in Spanish breast cancer families with male breast cancer

  • Ana Blanco
  • Miguel de la Hoya
  • Judith Balmaña
  • Teresa Ramón y Cajal
  • Alex Teulé
  • María-Dolores Miramar
  • Eva Esteban
  • Mar Infante
  • Javier Benítez
  • Asunción Torres
  • María-Isabel Tejada
  • Joan Brunet
  • Begoña Graña
  • Milagros Balbín
  • Pedro Pérez-Segura
  • Ana Osorio
  • Eladio A. Velasco
  • Isabel Chirivella
  • María-Teresa Calvo
  • Lidia Feliubadaló
  • Adriana Lasa
  • Orland Díez
  • Angel Carracedo
  • Trinidad Caldés
  • Ana VegaEmail author
Epidemiology

Abstract

It has been demonstrated that monoallelic PALB2 (Partner and Localizer of BRCA2) gene mutations predispose to familial breast cancer. Some of the families reported with germline PALB2 mutations presented male breast cancer as a characteristic clinical feature. Therefore, we wanted to investigate the contribution of germline PALB2 mutations in a set of 131 Spanish BRCA1/BRCA2-negative breast/ovarian cancer families with at least one male breast cancer case. The analysis included direct sequencing of all coding exons and intron/exon boundaries as well as a Multiplex Ligation-dependent Probe Amplification-based analysis of genomic rearrangements. For the first time we have identified a genomic rearrangement of PALB2 gene involving a large deletion from exon 7 to 11 in a breast cancer family. We have also identified several PALB2 variants, but no other obvious deleterious PALB2 mutation has been found. Thus, our study does not support an enrichment of PALB2 germline mutations in the subset of breast cancer families with male breast cancer cases. The identification of intronic and exonic variants indicates the necessity of assessing the implications of variants that do not lead to PALB2 truncation in the pathoghenicity of the PALB2 gene.

Keywords

Familial breast cancer PALB2 Male breast cancer Genomic rearrangement BRCA1/BRCA2-negative families In silico analysis 

Notes

Acknowledgments

We are grateful to the families for their cooperation and to the clinical personnel involved in aspects of recruitment and clinical data collection. This study was supported by grants from the Xunta de Galicia (10PXIB 9101297PR) and FMM Foundation given to AV. TC, M de H, and PPS were supported by PS09/00859, RD06/0020/0021 from RTICC, Instituto de Salud Carlos III. JB and AO were supports by the AECC, and RD06/0020/1060 from RTICC ICO: Contract grant sponsor: Asociación Española Contra el Cáncer, Spanish Health Research Fund; Carlos III Health Institute; Catalan Health Institute and Autonomous Government of Catalonia. Contract grant numbers: ISCIIIRETIC RD06/0020/1051, PI10/01422, PI10/31488, and 2009SGR290. E.V. grants, CSI004A10-2 (Consejería de Educación, Junta de Castilla y León) and BIO39/VA27/10 (Consejería de Sanidad, Junta de Castilla y León).

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

10549_2011_1842_MOESM1_ESM.docx (15 kb)
Supplementary material 1 (DOCX 14 kb)
10549_2011_1842_MOESM2_ESM.ppt (221 kb)
Supplementary Fig. 1. Co-segragation analysis of variants c.212-58A>C, c.1676A>G, c.2014G>C, c.2586 + 58C>T, c.2993G>A, c.3300T>G in one of the six carriers families. Individuals analyzed are indicated by + and − signs: carriers of all the six variants in heterozygous state are indicated with a + sign, individuals that were not carriers of any of the variants are indicated with a − sign. *One family member was heterozygous for variants c.1676A>G and c.2586 + 58C>T, only. Cancer diagnoses are indicated in the affected patient; in brackets the age at diagnosis or the actual age of the individual. (PPT 221 kb)

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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Ana Blanco
    • 1
  • Miguel de la Hoya
    • 2
  • Judith Balmaña
    • 3
  • Teresa Ramón y Cajal
    • 4
  • Alex Teulé
    • 5
  • María-Dolores Miramar
    • 6
  • Eva Esteban
    • 7
  • Mar Infante
    • 8
  • Javier Benítez
    • 9
  • Asunción Torres
    • 10
  • María-Isabel Tejada
    • 11
  • Joan Brunet
    • 12
  • Begoña Graña
    • 13
  • Milagros Balbín
    • 14
  • Pedro Pérez-Segura
    • 15
  • Ana Osorio
    • 9
  • Eladio A. Velasco
    • 8
  • Isabel Chirivella
    • 16
  • María-Teresa Calvo
    • 6
  • Lidia Feliubadaló
    • 5
  • Adriana Lasa
    • 17
  • Orland Díez
    • 18
  • Angel Carracedo
    • 1
  • Trinidad Caldés
    • 2
  • Ana Vega
    • 1
    • 19
    Email author
  1. 1.Fundación Pública Galega de Medicina Xenómica-SERGAS, Grupo de Medicina Xenómica-USCCIBER-ER, IDISSantiago de CompostelaSpain
  2. 2.Laboratorio de Oncología MolecularHospital Clínico San CarlosMadridSpain
  3. 3.Servicio de Oncología MédicaHospital Universitari Vall D’HebronBarcelonaSpain
  4. 4.Servei de OncologíaHospital de la Santa Creu i Sant PauBarcelonaSpain
  5. 5.Programa de Cáncer Hereditario, Instituto Catalán de OncologíaIDIBELL-ICO, L’Hospitalet de LlobregatBarcelonaSpain
  6. 6.Unidad de Genética. Servicio de BioquímicaHospital Universitario Miguel ServetZaragozaSpain
  7. 7.Laboratorio de Biología Molecular, Servicio de Análisis ClínicosHospital Universitario La FeValenciaSpain
  8. 8.Grupo de Genética del CáncerInstituto de Biología y Genética Molecular (UVa-CSIC)ValladolidSpain
  9. 9.Grupo de Genética HumanaCentro Nacional de Investigaciones Oncológicas-CNIO, CIBER-ER MadridMadridSpain
  10. 10.Unitat de Consell GenèticHospital Universitari Sant JoanReusSpain
  11. 11.Laboratorio de Genética Molecular-Servicio de BioquímicaHospital de CrucesBarakaldoSpain
  12. 12.Programa de Cáncer HereditarioInstitut Català d’Oncologia, IDIBGIGironaSpain
  13. 13.Oncoloxía Médica/UARC-Consello XenéticoHospital Arquitecto MarcideA CoruñaSpain
  14. 14.Laboratorio de Oncología Molecular-IUOPA (Instituto Universitario de Oncología del Principado de Asturias)Hospital Universitario Central de AsturiasOviedoSpain
  15. 15.Servicio de Oncología MédicaHospital Clínico San CarlosMadridSpain
  16. 16.Unidad de Consejo Genético en CáncerHospital Clínico UniversitarioValenciaSpain
  17. 17.Servei de GenèticaHospital de la Santa Creu i Sant PauBarcelonaSpain
  18. 18.Laboratori d’Oncogenetica. Vall d’Hebron Institut d’Oncologia (VHIO)Programa de Medicina Molecular. Hospital Universitari Vall d’HebronBarcelonaSpain
  19. 19.Fundación Pública Galega de Medicina XenómicaSantiago de CompostelaSpain

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