Skip to main content

Advertisement

SpringerLink
Log in

The deletion of exons 3–5 of BRCA1 is the first founder rearrangement identified in breast and/or ovarian cancer Spanish families

  • Short Communication
  • Published:
Familial Cancer Aims and scope Submit manuscript

Abstract

We recently described a novel g.8097_22733del14637 deletion encompassing exons 3–5 in BRCA1 gene. This rearrangement was detected in 3 of 15 (20 %) breast and/or ovarian cancer families of Eastern Spain. This finding made us suspect that the newly identified deletion could be a founder mutation. To confirm this hypothesis we studied 18 subjects belonging to the three families under study, 11 deletion carriers and 7 non-carriers. We performed a haplotype analysis using two BRCA1 intragenic microsatellite markers and two markers surrounding the BRCA1 locus. The segregation analysis showed one common particular haplotype established by D17S1325, D17S1323, D17S855 and D17S1320 markers detected in the deletion carriers but absent in the non-carriers. Our study sustain that the deletion of exons 3–5 of BRCA1, g.8097_22733del14637, identified in families of southeastern of the Valencian Community is the first founder rearrangement until now reported in Spanish population, confirming the hypothesis that this mutation could have Iberian ancestry.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

References

  1. Petrij-Bosch A, Peelen T, van Vliet M, van Eijk R, Olmer R, Drüsedau M, Hogervorst FB, Hageman S, Arts PJ, Ligtenberg MJ, Meijers-Heijboer H, Klijn JG, Vasen HF, Cornelisse CJ, van ‘t Veer LJ, Bakker E, van Ommen GJ, Devilee P (1997) BRCA1 genomic deletions are major founder mutations in Dutch breast cancer patients. Nat Genet 17:341–345

    Article  PubMed  CAS  Google Scholar 

  2. Sluiter MD, van Rensburg EJ (2011) Large genomic rearrangements of the BRCA1 and BRCA2 genes: review of the literature and report of a novel BRCA1 mutation. Breast Cancer Res Treat 125:325–349

    Article  PubMed  CAS  Google Scholar 

  3. Hogervorst FBL, Nederlof PM, Gille JJP, McElgunn CJ, Grippeling M, Pruntel R, Regnerus R, van Welsem T, van Spaendonk R, Menko FH, Kluijt I, Dommering C, Verhoef S, Schouten JP, van’t Veer LJ, Pals G (2003) Large genomic deletions and duplications in the BRCA1 gene identified by a novel quantitative method. Cancer Res 63:1449–1453

    PubMed  CAS  Google Scholar 

  4. van den Ouweland AM, Dinjens WN, Dorssers LC, van Veghel-Plandsoen MM, Brüggenwirth HT, Withagen-Hermans CJ, Collée JM, Joosse SA, Terlouw-Kromosoeto JN, Nederlof PM (2009) Deletion of exons 1a–2 of BRCA1: a rather frequent pathogenic abnormality. Genet Test Mol Biomarkers 13:399–406

    Article  PubMed  Google Scholar 

  5. Puget N, Sinilnikova OM, Stoppa-Lyonnet D, Audoynaud C, Pages S, Lynch HT, Goldgar D, Lenoir GM, Mazoyer S (1999) An Alu-mediated 6–kb duplication in the BRCA1 gene: a new founder mutation? Am J Hum Genet 64:300–302

    Article  PubMed  CAS  Google Scholar 

  6. The BRCA1 Exon 13 Duplication Screening Group (2000) The exon 13 duplication in the BRCA1 gene is a founder mutation present in geographically diverse populations. Am J Hum Genet 67:207–212

    Article  Google Scholar 

  7. Mazoyer S (2005) Genomic rearrangements in the BRCA1 and BRCA2 genes. Hum Mutat 25:415–422

    Article  PubMed  CAS  Google Scholar 

  8. Machado PM, Brandão RD, Cavaco BM, Eugénio J, Bento S, Nave M, Rodrigues P, Fernandes A, Vaz F (2007) Screening for a BRCA2 rearrangement in high-risk breast/ovarian cancer families: evidence for a founder effect and analysis of the associated phenotypes. J Clin Oncol 25:2027–2034

    Article  PubMed  CAS  Google Scholar 

  9. Peixoto A, Santos C, Rocha P, Pinheiro M, Príncipe S, Pereira D, Rodrigues H, Castro F, Abreu J, Gusmão L, Amorim A, Teixeira MR (2009) The c.156_157insAlu BRCA2 rearrangement accounts for more than one-fourth of deleterious BRCA mutations in northern/central Portugal. Breast Cancer Res Treat 114:31–38

    Article  PubMed  CAS  Google Scholar 

  10. Palanca Suela S, Esteban Cardeñosa E, Barragán González E, Oltra Soler S, de Juan Jiménez I, Chirivella González I, Segura Huerta A, Guillén Ponce C, de Martínez Dueñas E, Bolufer Gilabert P, Group for Assessment of Hereditary Cancer of Valencia Community (2008) Identification of a novel BRCA1 large genomic rearrangement in a Spanish breast/ovarian cancer family. Breast Cancer Res Treat 112:63–67

    Article  PubMed  CAS  Google Scholar 

  11. Rohlfs EM, Puget N, Graham ML, Weber BL, Garber JE, Skrzynia C, Halperin JL, Lenoir GM, Silverman LM, Mazoyer S (2000) An Alu-mediated 7.1 kb deletion of BRCA1 exons 8 and 9 in breast and ovarian cancer families that results in alternative splicing of exon 10. Genes Chromosomes Cancer 28:300–307

    Article  PubMed  CAS  Google Scholar 

  12. Berry DA, Parmigiani G, Sanchez J, Schildkraut J, Winer E (1997) Probability of carrying a mutation of breast-ovarian cancer gene BRCA1 based on family history. J Natl Cancer Inst 89:227–238

    Article  PubMed  CAS  Google Scholar 

  13. Parmigiani G, Berry DA, Aguilar O (1998) Determining carrier probabilities for breast cancer susceptibility genes BRCA1 and BRCA2. Am J Hum Genet 62:145–158

    Article  PubMed  CAS  Google Scholar 

  14. Antoniou AC, Pharoah PP, Smith P, Easton DF (2004) The BOADICEA model of genetic susceptibility to breast and ovarian cancer. Br J Cancer 91:1580–1590

    PubMed  CAS  Google Scholar 

  15. de la Hoya M, Gutiérrez-Enríquez S, Velasco E, Osorio A, de Abajo AS, Vega A, Salazar R, Esteban E, Llort G, Gonzalez-Sarmiento R, Carracedo A, Benitez J, Miner C, Diez O, Diaz-Rubio E, Caldes T (2006) Genomic rearrangements at the BRCA1 locus in Spanish families with breast/ovarian cancer. Clin Chem 52:1480–1485

    Article  PubMed  Google Scholar 

  16. Gutiérrez-Enríquez S, de la Hoya M, Martínez-Bouzas C, Sanchez de Abajo A, Ramón y Cajal T, Llort G, Blanco I, Beristain E, Díaz-Rubio E, Alonso C, Tejada MI, Caldés T, Diez O (2007) Screening for large rearrangements of the BRCA2 gene in Spanish families with breast/ovarian cancer. Breast Cancer Res Treat 103:103–107

    Article  PubMed  Google Scholar 

  17. Miramar MD, Calvo MT, Rodriguez A, Antón A, Lorente F, Barrio E, Herrero A, Burriel J, García de Jalón A (2008) Genetic analysis of BRCA1 and BRCA2 in breast/ovarian cancer families from Aragon (Spain): two novel truncating mutations and a large genomic deletion in BRCA1. Breast Cancer Res Treat 112:353–358

    Article  PubMed  CAS  Google Scholar 

  18. del Valle J, Feliubadaló L, Nadal M, Teulé A, Miró R, Cuesta R, Tornero E, Menéndez M, Darder E, Brunet J, Capellà G, Blanco I, Lázaro C (2010) Identification and comprehensive characterization of large genomic rearrangements in the BRCA1 and BRCA2 genes. Breast Cancer Res Treat 122:733–743

    Article  PubMed  Google Scholar 

  19. Thomassen M, Gerdes A-M, Cruger D, Jensen PKA, Kruse TA (2006) Low frequency of genomic rearrangements of BRCA1 and BRCA2 in western Denmark. Cancer Gen Cyto Genet 168:168–171

    Article  CAS  Google Scholar 

  20. Puget N, Stoppa-Lyonnet D, Sinilnikova OM, Pages S, Lynch HT, Lenoir GM, Mazoyer S (1999) Screening for genomic rearrangements and regulatory mutations in BRCA1 led to the identification of four new deletions. Cancer Res 59:455–461

    PubMed  CAS  Google Scholar 

  21. Gad S, Caux-Moncoutier V, Pages-Berhouet S, Gauthier-Villars M, Coupier I, Pujol P, Frenay M, Gilbert B, Maugard C, Bignon YJ, Chevrier A, Rossi A, Fricker JP, Nguyen TD, Demange L, Aurias A, Bensimon A, Stoppa-Lyonnet D (2002) Significant contribution of large BRCA1 gene rearrangements in 120 French breast and ovarian cancer families. Oncogene 21:6841–6847

    Article  PubMed  CAS  Google Scholar 

  22. Weitzel JN, Lagos VI, Herzog JS, Judkins T, Hendrickson B, Ho JS, Ricker CN, Lowstuter KJ, Blazer KR, Tomlinson G, Scholl T (2007) Evidence for a common ancestral origin of a recurring BRCA1 genomic rearrangement identified in high-risk Hispanic families. Cancer Epidemiol Biomarkers Prev 16:1615–1620

    Article  PubMed  CAS  Google Scholar 

  23. Montagna M, Palma MD, Menin C, Agata S, De Nicolo A, Chieco-Bianchi L, D’Andrea E (2003) Genomic rearrangements account for more than one-third of the BRCA1 mutations in northern Italian breast/ovarian cancer families. Hum Mol Genet 12:1055–1061

    Article  PubMed  CAS  Google Scholar 

  24. Teugels E, De Brakeleer S, Goelen G, Lissens W, Sermijn E, De Grève J (2005) De novo Alu element insertions targeted to a sequence common to the BRCA1 and BRCA2 genes. Hum Mutat 26:284

    Article  PubMed  Google Scholar 

  25. Hendrickson BC, Judkins T, Ward B, Eliason K, Deffenbaugh AE, Burbridge LA, Pyne K, Leclair B, Ward BE, Scholl T (2005) Prevalence of five previously reported and recurrent BRCA1 genetic rearrangement mutations in 20,000 patients from hereditary breast/ovarian cancer families. Genes Chromosomes Cancer 43:309–313

    Article  PubMed  CAS  Google Scholar 

  26. Montagna M, Santacatterina M, Torri A, Menin C, Zullato D, Chieco-Bianchi L, D’Andrea E (1999) Identification of a 3 kb Alu-mediated BRCA1 gene rearrangement in two breast/ovarian cancer families. Oncogene 18:4160–4165

    Article  PubMed  CAS  Google Scholar 

  27. Engert S, Wappenscmidt B, Betz B, Kast K, Kutsche M, Hellebrand H, Goecke TO, Kiechle M, Niederacher D, Schmutzler RK, Meindl A (2008) MLPA screening in the BRCA1 gene from 1,506 German hereditary breast cancer cases: novel deletions, frequent involvement of exon 17, and occurrence in single early onset cases. Hum Mutat 29:948–958

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We should express our gratitude to the ‘‘IIS La Fundación para la Investigación del Hospital Universitario La Fe’’ for giving economical support to Gema Perez Simó, what made possible their participation in the present study, and the ‘‘Fundación de Investigación de la Asociación Española contra el Cáncer’’.

Conflict of interest

The authors declared that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Laboratorio de Biología Molecular, Escuela de Enfermería 7ª planta, Hospital Universitario La Fe, Avd. Campanar 21, 46009, Valencia, Spain

    Sarai Palanca, Inmaculada de Juan, Gema Perez-Simó, Eva Barragán, Óscar Fuster & Pascual Bolufer

  2. Unit of Genetic Counselling in Cancer (Medical Oncology), University Clinical Hospital, Valencia, Spain

    Isabel Chirivella

  3. Unit of Genetic Counselling in Cancer (Medical Oncology), Consorcio Provincial Hospital, Castellón, Spain

    Eduardo Martínez

Authors
  1. Sarai Palanca
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Inmaculada de Juan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gema Perez-Simó
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Eva Barragán
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Isabel Chirivella
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Eduardo Martínez
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Óscar Fuster
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Pascual Bolufer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pascual Bolufer.

Additional information

This study was carried out on behalf of the Group for Assessment of Hereditary Cancer of Valencia Community.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Palanca, S., de Juan, I., Perez-Simó, G. et al. The deletion of exons 3–5 of BRCA1 is the first founder rearrangement identified in breast and/or ovarian cancer Spanish families. Familial Cancer 12, 119–123 (2013). https://doi.org/10.1007/s10689-012-9579-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10689-012-9579-6

Keywords

Search

Navigation