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Lack of correlation between survival and allele loss on chromosome 7q31–32 in primary breast cancer

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Pathology & Oncology Research

Abstract

High incidence of loss of heterozygosity (LOH), affecting the 7q31–32 chromosome region in sporadic primary human breast carcinomas suggests the presence of a tumor suppressor gene in this region which seems relevant to the development of breast cancer. To further determine the possible role of this region in the pathogenesis of human primary breast cancer and association with survival, LOH analysis was performed on 52 primary breast cancer patients using a set of highly polymorphic microsatellite markers. Our panel contained twenty biopsy cases of unknown survival, nineteen cases with more than five years survival and fourteen cases with less than two years survival. Corresponding normal and tumor DNAs were analyzed by polymerase chain reaction (PCR). The data presented here demonstrate that all patients were informative at least at one locus and 20 (38%) out of 53 cases showed LOH at one or more loci on chromosome 7q31–32. Relatively high incidence of LOH (34%) was detected at the D7S522 microsatellite marker located near to the cMet proto-oncogene while lower frequencies were observed at D7S523 (19%) and D7S495 (17%) loci, supporting the existence of a putative tumor suppressor gene at the chromosome 7q31.1 region. Our results suggest that allelic imbalance on 7q may occur at an early stage of breast carcinogenesis, as no correlation was observed between allelic loss and clinico-pathological data.

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References

  1. Ali IU, Lidereau R, Theillet C and Callahan R: Reduction to homozygosity of genes on chromosome 11 in human breast neoplasia. Science 238: 185–188. 1987.

    Article  PubMed  CAS  Google Scholar 

  2. Bièche I, Champème MH, Matifas F, Hacène K, Callahan R and Lidereau R: Loss of heterozvgosity on chromosome 7q and aggressive primary breast cancer. Lancet 339: 139–143, 1992.

    Article  PubMed  Google Scholar 

  3. Bièche I and Lidereau R: Loss of heterozygosity. chromosome 7q. and breast cancer - Reply. Lancet 339: 1423–1424. 1992.

    Article  Google Scholar 

  4. Burke RVP, Hutter PVP,and Henson DE: Breast carcinoma. In: “Prognostic factors in cancer”. (Eds.: Hermanek P. Gospodarowicz MK. Henson DE. Hutter RPV and Sobin LH). Springer Publ Co. 1995. pp. 165–176.

  5. Callahan R, Cropp CS, Merlo GR, Liscia DS, M.and Lidereau R: Somatic mutations and human breast cancer. A status report. Cancer 69: 1582–1588, 1992.

    Article  PubMed  CAS  Google Scholar 

  6. Champème M-H, Bièche I, Beuzelin M and Lidereau R: Loss of heterozygosity on 7q3l occurs early during breast tumorigenesis. Gene Chrom Cancer 12: 304–306. 1995.

    Article  Google Scholar 

  7. Cooke A, Kim YT, Harvey TI, Nagy J, and George WD: Loss of heterozygosity on chromosome 7q31 in breast cancer. Lancet 341: 1289, 1993.

    Article  PubMed  CAS  Google Scholar 

  8. Cornelisse CJ: Loss of heterozygosity, chromosome 7q. and breast cancer. Lancet 339: 1423, 1992.

    Article  PubMed  CAS  Google Scholar 

  9. Deng G, Chen L-C, Schott DR, Thor A, Bhargava V, Ljung B-M, Chew K and Smith HS: Loss of heterozygosity and p53 gene mutation in breast cancer. Cancer Res 54: 499–505, 1994.

    PubMed  CAS  Google Scholar 

  10. Devilee P and Cornelisse CJ: Somatic genetic changes in human breast cancer. Biochim Biophys Acta 1198: 113–130, 1994.

    PubMed  Google Scholar 

  11. Devilee P, Van Vliet M, Van Sloun P, et al: Allelotype of human breast carcinoma; a second major site for loss of heterozygosity is on chromosome 6q. Oncogene 6: 1705–1711. 1991.

    PubMed  CAS  Google Scholar 

  12. Klijn JGM, Berns EMJ,and Foekens JA: Prognostic factors and response to therapy in breast cancer. In: “Breast cancer”. (Eds.: Fentiman IS and Taylor-Papadimitriou). Cold Spring Harbor Laboratory Press Publ Co, 1995. pp. 165–198.

  13. Kelsey JN and Horn-Ross P: Breast cancer: magnitude of the problem and descriptive epidemiology. Epidemiol Rev 1: 7–16. 1993.

    Google Scholar 

  14. Kere J, Donis-Kelier H, Ruutu T and de la Chapelle A: Chromosome 7 long-arm deletions in myeloid disorders: terminal DNA sequences are commonly conserved and breakpoints vary. Cytogenet Cell Genet 50: 226–229, 1989.

    Article  PubMed  CAS  Google Scholar 

  15. Knudson AG: Antioneogenes and human cancer. Proc Natl Acad Sei USA 90: 10914–10921. 1993.

    Article  CAS  Google Scholar 

  16. Larsson C, Bystrom C, Skoog L, Rotstein S and Nordenskjold M: Genomic alteration in human breast carcinomas. Genes Chrom Cancer 2: 191–197, 1990.

    Article  PubMed  CAS  Google Scholar 

  17. Lundberg C, Skoog L, Cavenee WK and Nordenskjold M: Loss ol heterozygosity in human ductal breast tumors indicates a recessive mutation on chromosome 13. Proc Natl Acad Sei USA 84: 2372–2376. 1987.

    Article  CAS  Google Scholar 

  18. Ogata T, Ayusawa D, Namba M, Takahashi E, Oshimura M and Oishi M: Chromosome 7 suppresses indefinite division of nontumorigenic immortalized human fibroblast cell lines KMST-6 and SUSM-I. Mol Cell Biol 13: 6036–6043. 1993.

    PubMed  CAS  Google Scholar 

  19. Sato T, Akiyama F, Sakamoto G, Kasumi and Nakamura Y: Accumulation of genetic alteration and progression of primary breast cancer. Cancer Res 51: 5794–5799. 1991.

    PubMed  CAS  Google Scholar 

  20. Sato T, Saito H, Morita R, Koi S, Lee JH and Nakamura Y: Allelotype of human ovarian cancer. Cancer Res 51: 5118–5122. 1991.

    PubMed  CAS  Google Scholar 

  21. Sato T, Tanigami A, Yamakawa K, Akiyama F, Kasumi F, Sakamoto G and Nakamura Y: Allelotype of breast cancer: cumulative allele losses promote tumor progression in primary breast cancer. Cancer Res 50: 7184–7189, 1990.

    PubMed  CAS  Google Scholar 

  22. Tiainen M, Kere J, Taammilehto L, Mattson K and Knuutila S: Abnormalities of chromosomes 7 and 22 in human malignant pleural mesothelioma: correlation between Southern blot and cytogenetic analyses. Genes Chrom Cancer 4: 176–182, 1992.

    Article  PubMed  CAS  Google Scholar 

  23. Weinberg RA: Oncogenes, antioneogenes. and the molecular bases of multistep careinogenesis. Cancer Res 49: 3713–3721. 1989.

    PubMed  CAS  Google Scholar 

  24. Zenklusen JC, Bièche I, Lidereau R and Conti CJ: (C-A)n microsatellite repeat D7S522 is the most commonly deleted region in human primary breast cancer. Proc Natl Acad Sei USA 91: 12155–12158. 1994.

    Article  CAS  Google Scholar 

  25. Zenklusen JC, Oshimura M, Barrett JC and Conti CJ: Inhibition of tumorigenicity of a murine squamous cell carcinoma (SCC) cell line by a putative tumor suppressor gene on human chromosome 7. Oncogene 9: 2817–2825, 1994.

    PubMed  CAS  Google Scholar 

  26. Zenklusen JC, Thompson JC, Klein-Szanto AJ P.and Conti CJ: Frequent loss of heterozygosity in human primary squamous cell and colon carcinomas at 7q31.1: evidence for a broad range tumor suppressor gene. Cancer Res 55: 1347–1350, 1995.

    PubMed  CAS  Google Scholar 

  27. Zenklusen JC, Thompson JC, Troncoso P, Kagan J and Conti CJ: Loss of heterozygosity in human primary prostate carcinomas: a possible tumor suppressor gene at 7q31.1. Cancer Res 54: 6370–6373, 1994.

    PubMed  CAS  Google Scholar 

  28. Zenklusen JC, Weitzel JN, Ball HG and Conti CJ: Allelic loss at 7q31.1 in human primary ovarian carcinomas suggests the existence of a tumor suppressor gene. Oncogene 11: 359–363, 1995.

    PubMed  CAS  Google Scholar 

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This work was supported by Hungarian Research Grants ETT (T-019307) and OMFB (04-1-99-94-0328) given to Edith Olah.

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Sztán, M., Besznyák, I., Kovács, T. et al. Lack of correlation between survival and allele loss on chromosome 7q31–32 in primary breast cancer. Pathol. Oncol. Res. 2, 48–51 (1996). https://doi.org/10.1007/BF02893948

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  • DOI: https://doi.org/10.1007/BF02893948

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