Breast Cancer Research and Treatment

, Volume 124, Issue 2, pp 337–347 | Cite as

Screening for genomic rearrangements in BRCA1 and BRCA2 genes in Czech high-risk breast/ovarian cancer patients: high proportion of population specific alterations in BRCA1 gene

  • Ivana Ticha
  • Zdenek Kleibl
  • Jana Stribrna
  • Jaroslav Kotlas
  • Martina Zimovjanova
  • Martin Mateju
  • Michal Zikan
  • Petr PohlreichEmail author
Preclinical study


Large genomic rearrangements (LGR) represent substantial proportion of pathogenic mutations in the BRCA1 gene, whereas the frequency of rearrangements in the BRCA2 gene is low in many populations. We screened for LGRs in BRCA1 and BRCA2 genes by multiplex ligation-dependent probe amplification (MLPA) in 521 unrelated patients negative for BRCA1/2 point mutations selected from 655 Czech high-risk breast and/or ovarian cancer patients. Besides long range PCR, a chromosome 17-specific oligonucleotide-based array comparative genomic hybridization (aCGH) was used for accurate location of deletions. We identified 14 patients carrying 8 different LGRs in BRCA1 that accounted for 12.3% of all pathogenic BRCA1 mutations. No LGRs were detected in the BRCA2 gene. In a subgroup of 239 patients from high-risk families, we found 12 LGRs (5.0%), whereas two LGRs were revealed in a subgroup of 282 non-familial cancer cases (0.7%). Five LGRs (deletion of exons 1–17, 5–10, 13–19, 18–22 and 21–24) were novel; two LGRs (deletion of exons 5–14 and 21–22) belong to the already described Czech-specific mutations; one LGR (deletion of exons 1–2) was reported from several countries. The deletions of exons 1–17 and 5–14, identified each in four families, represented Czech founder mutations. The present study indicates that screening for LGRs in BRCA1 should include patients from breast or ovarian cancer families as well as high-risk patients with non-familial cancer, in particular cases with early-onset breast or ovarian cancer. On the contrary, our analyses do not support the need to screen for LGRs in the BRCA2 gene. Implementation of chromosome-specific aCGH could markedly facilitate the design of primers for amplification and sequence analysis of junction fragments, especially in deletions overlapping gene boundaries.


BRCA1 gene BRCA2 gene Large genomic rearrangements (LGR) Hereditary breast and ovarian cancer syndrome Multiplex ligation-dependent probe amplification (MLPA) Chromosome-specific array comparative genomic hybridization (aCGH) 



We thank Marie Epsteinova for her excellent technical assistance. Special thanks go to Zbynek Halbhuber PhD from KRD Molecular Technologies, who performed experiments with the oligonucleotide-based array CGH technique. This project was supported by the Internal Grant Agency of the Ministry of Health of the Czech Republic, Grant No. NS 10304-3/2009; and the Ministry of Education Youth and Sports Research Project: MSM 0021620808.


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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Ivana Ticha
    • 1
  • Zdenek Kleibl
    • 1
  • Jana Stribrna
    • 1
  • Jaroslav Kotlas
    • 2
  • Martina Zimovjanova
    • 3
  • Martin Mateju
    • 3
  • Michal Zikan
    • 1
    • 4
  • Petr Pohlreich
    • 1
    Email author
  1. 1.Institute of Biochemistry and Experimental Oncology, First Faculty of MedicineCharles University in PraguePrague 2Czech Republic
  2. 2.Institute of Biology and Medical Genetics, First Faculty of MedicineCharles University in Prague and General University Hospital in PraguePragueCzech Republic
  3. 3.Department of Oncology, First Faculty of MedicineCharles University in Prague and General University Hospital in PraguePragueCzech Republic
  4. 4.Department of Obstetrics and Gynecology, First Faculty of MedicineCharles University in Prague and General University Hospital in PraguePragueCzech Republic

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