Skip to main content

Advertisement

SpringerLink
Log in

Analysis of genome instability in breast cancer

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Breast cancer is a heterogeneous disease, previously associated with genomic instability. Our aim was to analyze microsatellite markers in order to determine patterns and levels of instability, as well as possible correlations with histopathological parameters. Polymerase chain reaction was used to characterize microsatellite instability (MSI) and loss of heterozygosity (LOH) in 107 breast carcinomas at twelve microsatellite loci. Some of the markers were selected because of their relation to steroid hormone metabolism, which seems to be related to sporadic breast cancer risk. D5S346 and D17S250 markers showed a statistically significant frequency of MSI. LOH in D3S1611, D17S250, AR and ER-β were associated with some parameters of worse prognosis. Marker group analysis showed that CYP19, AR and ER-β were related to histological grade III, ER-negative and PR-negative cases. Our results suggest that marker group analysis may be preferred to the single marker strategy, being predictive of worst prognosis when single markers are unable to provide such information. A further evaluation of steroid metabolism genes and their association with low penetrance genes in breast cancer may be useful.

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

Similar content being viewed by others

References

  1. Ashton-Prolla P, Giacomazzi J, Schmidt AV, Roth FL, Palmero EI, Kalakun L, Aguiar ES, Moreira Susana M, Batassini E, Belo-Reyes V, Schuler-Faccini L, Giugliani R, Caleffi M, Camey SA (2009) Development and validation of a simple questionnaire for the identification of hereditary breast cancer in primary care. BMC Cancer. doi:10.1186/1471-2407-9-283

    PubMed  Google Scholar 

  2. Conde J, Silva SN, Azevedo AP, Teixeira V, Pina JE, Rueff J, Gaspar JF (2009) Association of common variants in mismatch repair genes and breast cancer susceptibility: a multigene study. BMC Cancer. doi:10.1186/1471-2407-9-344

    PubMed  Google Scholar 

  3. Kelkar YD, Strubczewski N, Hile SE, Chiaromonte F, Eckert KA, Makova KD (2010) What is a microsatellite: a computational and experimental definition based upon repeat mutational behavior at A/T and GT/AC repeats. Genome Biol Evol 2:620–635

    Article  PubMed  Google Scholar 

  4. Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW, Meltzer SJ, Rodriguez-Bigas MA, Fodde R, Ranzani GN, Srivastava S (1998) A National Cancer Institute workshop on microsatellite instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res 58:5248–5257

    PubMed  CAS  Google Scholar 

  5. Lee S, Berg KD, Sherman ME, Griffin CA, Eshleman JR (2001) Microsatellite instability is infrequent in medullary breast cancer. Am J Clin Pathol 115:823–827

    Article  PubMed  CAS  Google Scholar 

  6. Peltomäki P (2003) Role of DNA mismatch repair defects in the pathogenesis of human cancer. J Clin Oncol 21:1174–1179

    Article  PubMed  Google Scholar 

  7. Ando Y, Iwase H, Ichihara S, Toyoshima S, Nakamura T, Yamashita H, Toyama T, Omoto Y, Karamatsu S, Mitsuyama S, Fujii Y, Kobayashi S (2000) Loss of heterozygosity and microsatellite instability in ductal carcinoma in situ of the breast. Cancer Lett 156:207–214

    Article  PubMed  CAS  Google Scholar 

  8. Thiagalingam S, Foy RL, Cheng KH, Lee HJ, Thiagalingam A, Ponte JF (2002) Loss of heterozygosity as a predictor to map tumor suppressor genes in cancer: molecular basis of its occurrence. Curr Opin Oncol 14:65–72

    Article  PubMed  CAS  Google Scholar 

  9. Schwarzenbach H, Müller V, Beeger C, Gottberg M, Stahmann N, Pantel K (2007) A critical evaluation of loss of heterozygosity detected in tumor tissues, blood serum and bone marrow plasma from patients with breast cancer. Breast Cancer Res. doi:10.1186/bcr1772

    PubMed  Google Scholar 

  10. Halford SE, Sawyer EJ, Lambros MB, Gorman P, Macdonald ND, Talbot IC, Foulkes WD, Gillett CE, Barnes DM, Akslen LA, Lee K, Jacobs IJ, Hanby AM, Ganesan TS, Salvesen HB, Bodmer WF, Tomlinson IP, Roylance RR (2003) MSI-low, a real phenomenon which varies in frequency among cancer types. J Pathol 201(3):389–394

    Article  PubMed  CAS  Google Scholar 

  11. Yee CJ, Roodi N, Verrier CS, Parl FF (1994) Microsatellite instability and loss of heterozygosity in breast cancer. Cancer Res 54:1641–1644

    PubMed  CAS  Google Scholar 

  12. Tokunaga E, Okada S, Yamashita N, Akiyoshi S, Kitao H, Morita M, Kakeji Y, Maehara Y (2012) High incidence and frequency of LOH are associated with aggressive features of high-grade HER2 and triple-negative breast cancers. Breast Cancer 19(2):161–169

    Article  PubMed  Google Scholar 

  13. Saleh EM, Wahab AH, Elhouseini ME, Eisa SS (2004) Loss of heterozygosity at BRCA1, TP53, nm-23 and other loci on chromosome 17q in human breast carcinoma. J Egypt Natl Canc Inst 16(1):62–68

    PubMed  Google Scholar 

  14. Anghel A, Raica M, Marian C, Ursoniu S, Mitrasca O (2006) Combined profile of the tandem repeats CAG, TA and CA of the androgen and estrogen receptor genes in breast cancer. J Cancer Res Clin Oncol 132(11):727–733

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Part of this study was sponsored by Fibria Celulose. E.V. Wolfgramm was supported by a FAPES doctorate scholarship. L. N. R. Alves, E. Stur, T. T. Tovar and M. P. D. N. Sartori were supported by a CNPq scholarships.

Author information

Authors and Affiliations

  1. Núcleo de Genética Humana e Molecular, Departamento de Ciências Biológicas, Centro de Ciências Humanas e Naturais, Universidade Federal do Espirito Santo, Av. Marechal Campos, 1468, Campus de Maruípe, Vitoria, ES, 29040-090, Brazil

    Eldamária de Vargas Wolfgramm, Lyvia Neves Rebello Alves, Elaine Stur, Thaís Tristão Tovar, Mariana Penha De Nadai Sartori & Iúri Drumond Louro

  2. Serviço de Patologia, Hospital Santa Rita de Cássia, Avenida Marechal Campos, 1579, Santa Cecília, Vitoria, 29043-260, ES, Brazil

    Allan Kardec de Castro Neto

Authors
  1. Eldamária de Vargas Wolfgramm
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lyvia Neves Rebello Alves
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Elaine Stur
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Thaís Tristão Tovar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mariana Penha De Nadai Sartori
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Allan Kardec de Castro Neto
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Iúri Drumond Louro
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Iúri Drumond Louro.

Rights and permissions

Reprints and permissions

About this article

Cite this article

de Vargas Wolfgramm, E., Alves, L.N.R., Stur, E. et al. Analysis of genome instability in breast cancer. Mol Biol Rep 40, 2139–2144 (2013). https://doi.org/10.1007/s11033-012-2272-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-012-2272-x

Keywords

Search

Navigation