Skip to main content

Advertisement

Log in

Genomic instability in invasive breast carcinoma measured by inter-Simple Sequence Repeat PCR

  • brief Communication
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Summary

We have measured genomic instability in invasive breast carcinomas and assessed the relationship of genomic instability to known tumor prognostic factors. DNAs from tumors and adjacent normal tissue of 18 breast cancer patients were subjected to inter-Simple Sequence Repeat (inter-SSR) PCR for quantitation of tumor genomic instability. Associations between genomic instability level and known breast cancer prognostic factors were evaluated using the Pearson Product Moment Correlation, the Kruskal–Wallis test of independent samples and the Mann–Whitney non-parametric test. Genomic instability was detected by inter-SSR PCR in over 90% of the breast tumors. The mean instability index was 3.08% (0–7.59%), approximately the same mean value observed in studies of colorectal and thyroid carcinomas. Significantly higher levels of instability were associated with tumors exhibiting necrosis. Genomic instability as measured is detected in the majority of breast cancers at levels comparable to other tumor types. Hypoxia, such as that observed in necrotic regions of tumors, has been associated with elevated genomic damage. We hypothesize that the higher levels of genomic instability detected in necrotic tumors is a consequence of hypoxia-associated DNA damage.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Anderson GR, Stoler DL, Brenner BM, 2001 Cancer: the evolved consequence of a destabilized genome BioEssays 23: 1037–1046

    Article  CAS  PubMed  Google Scholar 

  2. Hanahan D, Weinberg RA, 2000 The hallmarks of cancer Cell 100: 57–70

    Article  CAS  PubMed  Google Scholar 

  3. Fearon ER, Vogelstein B, 1990 A genetic model for colorectal tumorigenesis Cell 61: 759–767

    Article  CAS  PubMed  Google Scholar 

  4. Renan MJ, 1993 How many mutations are required for tumorigenesis? Implications from human cancer data Mol Carcinogen 7: 139–146

    Article  CAS  Google Scholar 

  5. Loeb LA, 1991 Mutator phenotype may be required for multistage carcinogenesis Cancer Res 51:3075–3079

    CAS  PubMed  Google Scholar 

  6. Jackson AL, Loeb LA, 1998 The mutation rate and cancer Genetics 148: 1483–1490

    CAS  PubMed  Google Scholar 

  7. Loeb LA, 2001 A mutator phenotype in cancer Cancer Res 61: 3230–3239

    CAS  PubMed  Google Scholar 

  8. Greenlee RT, Murray T, Bolden S, Wingo PA, 2000 Cancer Statistics, 2000 CA Cancer J Clin 50: 7–33

    Article  CAS  PubMed  Google Scholar 

  9. Alberg AJ, Singh S, May JW, Helzlsouer KJ, 2000 Epidemiology, prevention and early detection of breast cancer Curr Opin Oncol 12: 515–520

    Article  CAS  PubMed  Google Scholar 

  10. Wolff AC, Davidson NE, 2000 Primary systemic therapy in operable breast cancer J Clin Oncol 18: 1558–1569

    CAS  PubMed  Google Scholar 

  11. Basik M, Stoler DL, Kontzoglou KC, Rodriguez-Bigas MA, Petrelli NJ, Anderson GR, 1997 Genomic instability in sporadic colorectal cancer quantitated by inter-(simple sequence repeat) PCR analysis Gene Chromosome Canc 18: 19–29

    Article  CAS  Google Scholar 

  12. Winer EP, Morrow M, Osborne CK, Harris JR, 2001 Malignant tumors of the breast. In:DeVita VT, Hellman S, Rosenberg SA, eds. Cancer: Principles and Practice of Oncology, 6, Williams & Wilkins, Philadelphia, PA: Lippincott, pp 1651–1716

    Google Scholar 

  13. Przybytkowski E, Girouard S, Allard B, Lamarre L, Basik M, 2003 Widespread bimodal intrachromosomal genomic instability in sporadic breast cancers associated with 13q allelic imbalance Cancer Res 63:4588–4593

    CAS  PubMed  Google Scholar 

  14. Stoler DL, Chen N, Basik M, Kahlenberg MS, Rodriguez-Bigas MA, Petrelli NJ, Anderson GR, 1999 The onset and extent of genomic instability in sporadic colorectal tumor progression Proc Natl Acad Sci USA 96: 15121–15126

    Article  CAS  PubMed  Google Scholar 

  15. Wiseman SM, Loree TR, Rigual NR, Hicks WL Jr, Winston JS, Swede H, Bartos JD, Anderson GR, Stoler DL, 2003 Papillary thyroid cancer: high inter-(simple sequence repeat) genomic instability in a typically indolent cancer Head Neck 25:825–832

    Article  PubMed  Google Scholar 

  16. Thomlinson RH, Gray LH, 1955 The histological structure of some human lung cancers and the possible implications for radiotherapy Brit J Cancer 9: 539–549

    CAS  PubMed  Google Scholar 

  17. Russo CA, Weber TK, Volpe CM, Stoler DL, Petrelli NJ, Rodriguez-Bigas M, Burhans WC, Anderson GR, 1995 An anoxia inducible endonuclease and enhanced DNA breakage as contributors to genomic instability in cancer Cancer Res 55:1122–1128

    CAS  PubMed  Google Scholar 

  18. Reynolds TY, Rockwell S, Glazer PM, 1996 Genetic instability induced by the tumor microenvironment Cancer Res 56: 5754–5757

    CAS  PubMed  Google Scholar 

  19. Nelson DA, Tan TT, Rabson AB, Anderson D, Degenhardt K, White E, 2004 Hypoxia and defective apoptosis drive genomic instability and tumorigenesis Genes Dev 18:2095–2107

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by American Cancer Society Grant No. RPG-98-192-01-CNE (DLS) and NIH grant RO1 CA74127(GRA), and partially supported by shared resources of the Roswell Park Cancer Center support Grant P30 CA16056. We thank Nancy Watroba for her invaluable assistance in collecting patient data.

Author information

Authors and Affiliations

Authors

Additional information

Daniel L. Stoler, Jeremy D. Bartos, and Helen Swede all contributed equally to this manuscript

Rights and permissions

Reprints and permissions

About this article

Cite this article

Stoler, D.L., Bartos, J.D., Swede, H. et al. Genomic instability in invasive breast carcinoma measured by inter-Simple Sequence Repeat PCR. Breast Cancer Res Treat 97, 107–110 (2006). https://doi.org/10.1007/s10549-005-9092-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-005-9092-9

Keywords

Navigation