Familial Cancer

, Volume 13, Issue 2, pp 205–211 | Cite as

Large genomic rearrangement of BRCA1 and BRCA2 genes in familial breast cancer patients in Korea

  • Ja Young Cho
  • Dae-Yeon Cho
  • Sei Hyun Ahn
  • Su-Youn Choi
  • Inkyung Shin
  • Hyun Gyu Park
  • Jong Won Lee
  • Hee Jeong Kim
  • Jong Han Yu
  • Beom Seok Ko
  • Bo Kyung Ku
  • Byung Ho SonEmail author
Original Article


We screened large genomic rearrangements of the BRCA1 and BRCA2 genes in Korean, familial breast cancer patients. Multiplex ligation-dependent probe amplification assay was used to identify BRCA1 and BRCA2 genomic rearrangements in 226 Korean familial breast cancer patients with risk factors for BRCA1 and BRCA2 mutations, who previously tested negative for point mutations in the two genes. We identified only one large deletion (c.4186-1593_4676-1465del) in BRCA1. No large rearrangements were found in BRCA2. Our result indicates that large genomic rearrangement in the BRCA1 and BRCA2 genes does not seem like a major determinant of breast cancer susceptibility in the Korean population. A large-scale study needs to validate our result in Korea.


BRCA1 BRCA2 Hereditary breast cancer Korean population Large genomic rearrangement 



This study was supported by a grant from the Industrial Strategic Technology Development Program funded by the Ministry of Knowledge Economy (#10038662), Republic of Korea, and a Grant (09-364) from the Asan Institute for Life Sciences, Seoul, Korea.

Conflict of interest

The authors have no competing financial interests or conflicts of interest to declare.


  1. 1.
    Iwasaki M, Tsugane S (2011) Risk factors for breast cancer: epidemiological evidence from Japanese studies. Cancer Sci 102(9):1607–1614. doi: 10.1111/j.1349-7006.2011.01996.x PubMedCrossRefGoogle Scholar
  2. 2.
    Jemal A, Center MM, DeSantis C, Ward EM (2010) Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol Biomarkers Prev 19(8):1893–1907. doi: 10.1158/1055-9965.EPI-10-0437 PubMedCrossRefGoogle Scholar
  3. 3.
    Natioinal Cancer Institute SEER cancer statistics review 1975–2007. Accessed 6 Sep 2010
  4. 4.
    Jung YS, Na KY, Kim KS et al (2011) Nation-wide Korean breast cancer data from 2008 using the breast cancer registration program. J Breast Cancer 14(3):229–236. doi: 10.4048/jbc.2011.14.3.229 PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Ford D, Easton DF (1995) The genetics of breast and ovarian cancer. Br J Cancer 72(4):805–812PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Wooster R, Bignell G, Lancaster J et al (1995) Identification of the breast cancer susceptibility gene BRCA2. Nature 378(6559):789–792. doi: 10.1038/378789a0 PubMedCrossRefGoogle Scholar
  7. 7.
    Miki Y, Swensen J, Shattuck-Eidens D et al (1994) A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 266(5182):66–71PubMedCrossRefGoogle Scholar
  8. 8.
    Brody LC, Biesecker BB (1998) Breast cancer susceptibility genes. BRCA1 and BRCA2. Medicine (Baltimore) 77(3):208–226CrossRefGoogle Scholar
  9. 9.
    Unger MA, Nathanson KL, Calzone K et al (2000) Screening for genomic rearrangements in families with breast and ovarian cancer identifies BRCA1 mutations previously missed by conformation-sensitive gel electrophoresis or sequencing. Am J Hum Genet 67(4):841–850PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Puget N, Torchard D, Serova-Sinilnikova OM et al (1997) A 1-kb Alu-mediated germ-line deletion removing BRCA1 exon 17. Cancer Res 57(5):828–831PubMedGoogle Scholar
  11. 11.
    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(2):325–349. doi: 10.1007/s10549-010-0817-z PubMedCrossRefGoogle Scholar
  12. 12.
    Montagna M, Dalla Palma M, Menin C et al (2003) Genomic rearrangements account for more than one-third of the BRCA1 mutations in northern Italian breast/ovarian cancer families. Hum Mol Genet 12(9):1055–1061PubMedCrossRefGoogle Scholar
  13. 13.
    Moisan AM, Fortin J, Dumont M et al (2006) No Evidence of BRCA1/2 genomic rearrangements in high-risk French-Canadian breast/ovarian cancer families. Genet Test 10(2):104–115. doi: 10.1089/gte.2006.10.104 PubMedCrossRefGoogle Scholar
  14. 14.
    Walsh T, Casadei S, Coats KH 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. doi: 10.1001/jama.295.12.1379 PubMedCrossRefGoogle Scholar
  15. 15.
    Mazoyer S (2005) Genomic rearrangements in the BRCA1 and BRCA2 genes. Hum Mutat 25(5):415–422. doi: 10.1002/humu.20169 PubMedCrossRefGoogle Scholar
  16. 16.
    Yap KP, Ang P, Lim IH, Ho GH, Lee AS (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. doi: 10.1111/j.1399-0004.2006.00637.x PubMedCrossRefGoogle Scholar
  17. 17.
    Miki Y, Katagiri T, Kasumi F, Yoshimoto T, Nakamura Y (1996) Mutation analysis in the BRCA2 gene in primary breast cancers. Nat Genet 13(2):245–247. doi: 10.1038/ng0696-245 PubMedCrossRefGoogle Scholar
  18. 18.
    Lim YK, Lau PT, Ali AB 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. doi: 10.1111/j.1399-0004.2007.00773.x PubMedCrossRefGoogle Scholar
  19. 19.
    Kang P, Mariapun S, Phuah SY et al (2010) Large BRCA1 and BRCA2 genomic rearrangements in Malaysian high risk breast-ovarian cancer families. Breast Cancer Res Treat 124(2):579–584. doi: 10.1007/s10549-010-1018-5 PubMedCrossRefGoogle Scholar
  20. 20.
    Seong MW, Cho SI, Noh DY 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. doi: 10.1007/s10689-009-9279-z PubMedCrossRefGoogle Scholar
  21. 21.
    Gad S, Scheuner MT, Pages-Berhouet S et al (2001) Identification of a large rearrangement of the BRCA1 gene using colour bar code on combed DNA in an American breast/ovarian cancer family previously studied by direct sequencing. J Med Genet 38(6):388–392PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Thomassen M, Gerdes AM, Cruger D, Jensen PK, Kruse TA (2006) Low frequency of large genomic rearrangements of BRCA1 and BRCA2 in western Denmark. Cancer Genet Cytogenet 168(2):168–171. doi: 10.1016/j.cancergencyto.2005.12.016 PubMedCrossRefGoogle Scholar
  23. 23.
    Engert S, Wappenschmidt B, Betz B 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. doi: 10.1002/humu.20723 PubMedCrossRefGoogle Scholar
  24. 24.
    Smith TM, Lee MK, Szabo CI et al (1996) Complete genomic sequence and analysis of 117 kb of human DNA containing the gene BRCA1. Genome Res 6(11):1029–1049PubMedCrossRefGoogle Scholar
  25. 25.
    Machado PM, Brandao RD, Cavaco BM et al (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(15):2027–2034. doi: 10.1200/JCO.2006.06.9443 PubMedCrossRefGoogle Scholar
  26. 26.
    Agata S, Dalla Palma M, Callegaro M et al (2005) Large genomic deletions inactivate the BRCA2 gene in breast cancer families. J Med Genet 42(10):e64. doi: 10.1136/jmg.2005.032789 PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Bunyan DJ, Eccles DM, Sillibourne J et al (2004) Dosage analysis of cancer predisposition genes by multiplex ligation-dependent probe amplification. Br J Cancer 91(6):1155–1159. doi: 10.1038/sj.bjc.6602121 PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Hartmann C, John AL, Klaes R et al (2004) Large BRCA1 gene deletions are found in 3% of German high-risk breast cancer families. Hum Mutat 24(6):534. doi: 10.1002/humu.9291 PubMedCrossRefGoogle Scholar
  29. 29.
    Palma MD, Domchek SM, Stopfer J et al (2008) The relative contribution of point mutations and genomic rearrangements in BRCA1 and BRCA2 in high-risk breast cancer families. Cancer Res 68(17):7006–7014. doi: 10.1158/0008-5472.CAN-08-0599 PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Han SA, Park SK, Ahn SH et al (2011) The Korean Hereditary Breast Cancer (KOHBRA) study: protocols and interim report. Clin Oncol (R Coll Radiol) 23(7):434–441. doi: 10.1016/j.clon.2010.11.007 CrossRefGoogle Scholar
  31. 31.
    Seo JH, Cho DY, Ahn SH et al (2004) BRCA1 and BRCA2 germline mutations in Korean patients with sporadic breast cancer. Hum Mutat 24(4):350. doi: 10.1002/humu.9275 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Ja Young Cho
    • 1
  • Dae-Yeon Cho
    • 2
  • Sei Hyun Ahn
    • 1
  • Su-Youn Choi
    • 2
  • Inkyung Shin
    • 2
  • Hyun Gyu Park
    • 3
  • Jong Won Lee
    • 1
  • Hee Jeong Kim
    • 1
  • Jong Han Yu
    • 1
  • Beom Seok Ko
    • 1
  • Bo Kyung Ku
    • 1
  • Byung Ho Son
    • 1
    Email author
  1. 1.Division of Breast and Endocrine Surgery, Department of Surgery College of Medicine, University of UlsanAsan Medical CenterSeoulKorea
  2. 2.LabGenomics Clinical Research InstituteLabGenomicsSeongnamKorea
  3. 3.Department of Chemical and Biomolecular EngineeringKAISTDaejeonKorea

Personalised recommendations