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Large BRCA1 and BRCA2 genomic rearrangements in Malaysian high risk breast-ovarian cancer families

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Abstract

Early studies of genetic predisposition due to the BRCA1 and BRCA2 genes have focused largely on sequence alterations, but it has now emerged that 4–28% of inherited mutations in the BRCA genes may be due to large genomic rearrangements of these genes. However, to date, there have been relatively few studies of large genomic rearrangements in Asian populations. We have conducted a full sequencing and large genomic rearrangement analysis (using Multiplex Ligation-dependent Probe Amplification, MLPA) of 324 breast cancer patients who were selected from a multi-ethnic hospital-based cohort on the basis of age of onset of breast cancer and/or family history. Three unrelated individuals were found to have large genomic rearrangements: 2 in BRCA1 and 1 in BRCA2, which accounts for 2/24 (8%) of the total mutations detected in BRCA1 and 1/23 (4%) of the mutations in BRCA2 detected in this cohort. Notably, the family history of the individuals with these mutations is largely unremarkable suggesting that family history alone is a poor predictor of mutation status in Asian families. In conclusion, this study in a multi-ethnic (Malay, Chinese, Indian) cohort suggests that large genomic rearrangements are present at a low frequency but should nonetheless be included in the routine testing for BRCA1 and BRCA2.

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References

  1. Mazoyer S (2005) Genomic rearrangements in the BRCA1 and BRCA2 genes. Hum Mutat 25(5):415–422

    Article  CAS  PubMed  Google Scholar 

  2. Sluiter MD, van Rensburg EJ (2010) Large genomic rearrangements of the BRCA1 and BRCA2 genes: review of the literature and report of a novel BRCA1 mutation. Breast Cancer Res Treat. doi:10.1007/s10549-010-0817-z

  3. Kwong A et al (2009) A BRCA2 founder mutation and seven novel deleterious BRCA mutations in southern Chinese women with breast and ovarian cancer. Breast Cancer Res Treat 117(3):683–686

    Article  PubMed  Google Scholar 

  4. Lim YK et al (2007) Identification of novel BRCA large genomic rearrangements in Singapore Asian breast and ovarian patients with cancer. Clin Genet 71(4):331–342

    Article  CAS  PubMed  Google Scholar 

  5. Ang P et al (2007) BRCA1 and BRCA2 mutations in an Asian clinic-based population detected using a comprehensive strategy. Cancer Epidemiol Biomarkers Prev 16(11):2276–2284

    Article  CAS  PubMed  Google Scholar 

  6. Yap KP et al (2006) Detection of a novel Alu-mediated BRCA1 exon 13 duplication in Chinese breast cancer patients and implications for genetic testing. Clin Genet 70(1):80–82

    Article  PubMed  Google Scholar 

  7. Seong MW et al (2009) Low contribution of BRCA1/2 genomic rearrangement to high-risk breast cancer in the Korean population. Fam Cancer 8(4):505–508

    Article  CAS  PubMed  Google Scholar 

  8. Miki Y et al (1996) Mutation analysis in the BRCA2 gene in primary breast cancers. Nat Genet 13(2):245–247

    Article  CAS  PubMed  Google Scholar 

  9. Sharifah NA, et al (2010) Identification of novel large genomic rearrangements at the BRCA1 locus in Malaysian women with breast cancer. Cancer Epidemiol. doi:10.1016/j.canep.2010.04.010

  10. Thirthagiri E et al (2008) Evaluation of BRCA1 and BRCA2 mutations and risk-prediction models in a typical Asian country (Malaysia) with a relatively low incidence of breast cancer. Breast Cancer Res 10(4):R59

    Article  CAS  PubMed  Google Scholar 

  11. Rao NY et al (2009) Evaluating the performance of models for predicting the BRCA germline mutations in Han Chinese familial breast cancer patients. Breast Cancer Res Treat 116(3):563–570

    Article  PubMed  Google Scholar 

  12. Toh GT et al (2008) BRCA1 and BRCA2 germline mutations in Malaysian women with early-onset breast cancer without a family history. PLoS One 3(4):e2024

    Article  PubMed  Google Scholar 

  13. Colella S et al (2007) QuantiSNP: an objective Bayes Hidden–Markov Model to detect and accurately map copy number variation using SNP genotyping data. Nucleic Acids Res 35(6):2013–2025

    Article  CAS  PubMed  Google Scholar 

  14. Walsh T et al (2006) Spectrum of mutations in BRCA1, BRCA2, CHEK2, and TP53 in families at high risk of breast cancer. JAMA 295(12):1379–1388

    Article  CAS  PubMed  Google Scholar 

  15. Ratajska M et al (2008) BRCA1 and BRCA2 point mutations and large rearrangements in breast and ovarian cancer families in Northern Poland. Oncol Rep 19(1):263–268

    CAS  PubMed  Google Scholar 

  16. Hansen TO et al (2009) Large BRCA1 and BRCA2 genomic rearrangements in Danish high risk breast-ovarian cancer families. Breast Cancer Res Treat 115(2):315–323

    Article  CAS  PubMed  Google Scholar 

  17. Pylkas K et al (2008) Analysis of large deletions in BRCA1, BRCA2 and PALB2 genes in Finnish breast and ovarian cancer families. BMC Cancer 8:146

    Article  PubMed  Google Scholar 

  18. Engert S et al (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(7):948–958

    Article  CAS  PubMed  Google Scholar 

  19. Miramar MD et al (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(2):353–358

    Article  CAS  PubMed  Google Scholar 

  20. Purnomosari D et al (2007) BRCA1 and BRCA2 germline mutation analysis in the Indonesian population. Breast Cancer Res Treat 106(2):297–304

    Article  CAS  PubMed  Google Scholar 

  21. Veschi S et al (2007) High prevalence of BRCA1 deletions in BRCAPRO-positive patients with high carrier probability. Ann Oncol 18(6):vi86–vi92

    Article  PubMed  Google Scholar 

  22. Vasickova P et al (2007) High occurrence of BRCA1 intragenic rearrangements in hereditary breast and ovarian cancer syndrome in the Czech Republic. BMC Med Genet 8:32

    Article  PubMed  Google Scholar 

  23. Gutierrez-Enriquez S et al (2007) Screening for large rearrangements of the BRCA2 gene in Spanish families with breast/ovarian cancer. Breast Cancer Res Treat 103(1):103–107

    Article  PubMed  Google Scholar 

  24. Palanca Suela S et al (2008) Identification of a novel BRCA1 large genomic rearrangement in a Spanish breast/ovarian cancer family. Breast Cancer Res Treat 112(1):63–67

    Article  CAS  PubMed  Google Scholar 

  25. Weitzel JN et al (2007) Evidence for common ancestral origin of a recurring BRCA1 genomic rearrangement identified in high-risk Hispanic families. Cancer Epidemiol Biomarkers Prev 16(8):1615–1620

    Article  CAS  PubMed  Google Scholar 

  26. Casilli F et al (2006) The contribution of germline rearrangements to the spectrum of BRCA2 mutations. J Med Genet 43(9):e49

    Article  CAS  PubMed  Google Scholar 

  27. Buffone A et al (2007) Prevalence of BRCA1 and BRCA2 genomic rearrangements in a cohort of consecutive Italian breast and/or ovarian cancer families. Breast Cancer Res Treat 106(2):289–296

    Article  CAS  PubMed  Google Scholar 

  28. Armaou S et al (2007) Novel genomic rearrangements in the BRCA1 gene detected in Greek breast/ovarian cancer patients. Eur J Cancer 43(2):443–453

    Article  CAS  PubMed  Google Scholar 

  29. Tournier I et al (2004) Significant contribution of germline BRCA2 rearrangements in male breast cancer families. Cancer Res 64(22):8143–8147

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank participants and their families for taking part in this study and Lee Sheau Yee, Eswary Thirthagiri and Daphne Lee for assistance with DNA preparation, pathology data and helpful discussions. This study was funded by research grants from the Malaysian Ministry of Science, Technology and Innovation, University Malaya and Cancer Research Initiatives Foundation.

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Correspondence to Soo-Hwang Teo.

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Kang, P., Mariapun, S., Phuah, S.Y. et al. Large BRCA1 and BRCA2 genomic rearrangements in Malaysian high risk breast-ovarian cancer families. Breast Cancer Res Treat 124, 579–584 (2010). https://doi.org/10.1007/s10549-010-1018-5

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  • DOI: https://doi.org/10.1007/s10549-010-1018-5

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