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Prognostic significance of loss of heterozygosity at loci on chromosome 17p13.3-ter in sporadic breast cancer is evidence for a putative tumour suppressor gene
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  • Published: 23 April 1999

Prognostic significance of loss of heterozygosity at loci on chromosome 17p13.3-ter in sporadic breast cancer is evidence for a putative tumour suppressor gene

  • D S Liscia1,
  • R Morizio1,
  • T Venesio1,
  • C Palenzona1,
  • M Donadio1 &
  • …
  • R Callahan2 

British Journal of Cancer volume 80, pages 821–826 (1999)Cite this article

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Summary

Several studies indicate that the short arm of chromosome 17 is one of the most frequently altered regions in sporadic breast carcinomas (45–60%). In the present report the 17p13.3-ter locus in tumour DNA of breast cancer patients, along with their matching normal lymphocyte DNA, have been mapped with four markers (D17S5, D17S379, ABR and D17S34), spanning nearly 3 cM of the telomer. Sixty-five of 143 heterozygous tumours had lost at least one of the markers at the minimum region of loss (45%). High levels of loss of these distal markers on 17p13.3 are independent of TP53 mutations and are associated with tumour cell proliferation. A follow-up period of over 7 years demonstrates that loss of these markers correlates both with disease-free (P = 0.004) and overall survival (P = 0.007). In addition we show that for disease-free survival the prognostic power of this genetic alteration is second only to axillary lymph node involvement (3.1 vs 6.3 relative risk), and is a better predictor than the mutational status of TP53 (1.6 relative risk). Our results are further evidence of the presence, within the region, of at least a second tumour suppressor gene distal to TP53, that might be targeted by deletions.

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  • 16 November 2011

    This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication

References

  • Bonadonna, G., Valagussa, P., Tancini, G., Rossi, A., Brambilla, C., Zambetti, M., Bignami, P., Di Fronzo, G. & Silvestrini, R. (1986). Current status of Milan adjuvant chemotherapy trials for node-positive and node-negative breast cancer. Natl Cancer Inst Monogr 1: 45–49.

    Google Scholar 

  • Carrozzo, R. & Ledbetter, D. H. (1993). Dinucleotide repeat polymorphism mapping to the critical region for lissencephaly (17p 13.3). Hum Mol Genet 2: 615

    Article  CAS  Google Scholar 

  • Coles, C., Thompson, A. M., Elder, P. A., Cohen, B. B., Mackenzie, I. M., Cranston, G., Chetty, U., Mackay, J., Macdonald, M., Nakamura, Y., Hoyheim, B. & Steel, C. M. (1990). Evidence implicating at least two genes on chromosome 17p in breast carcinogenesis. Lancet 336: 761–763.

    Article  CAS  Google Scholar 

  • Cox, D. R. (1972). Regression models and life tables. J R Stat Soc 34: 187–220.

    Google Scholar 

  • Gudmundsson, J., Johannesdottir, G., Bergthorsson, J. T., Arason, A., Ingvarsson, S., Egilsson, V. & Barkardottir, R. B. (1995). Different tumor types from BRCA2 carriers show wild-type chromosome deletions on 13q12–q13. Cancer Res 55: 4830–4832.

    CAS  PubMed  Google Scholar 

  • Heisterkamp, N., Kaartinen, V., van Soest, S., Bokoch, G. M. & Groffen, J. (1993). Human ABR encodes a protein with GAP-rac activity and homology to the DBL nucleotide exchange factor domain. J Biol Chem 268: 16903–16906.

    CAS  PubMed  Google Scholar 

  • Isomura, M., Tanigami, A., Saito, H., Harada, Y., Katagiri, T., Inazawa, J., Ledbetter, D. H. & Nakamura, Y. (1994). Detailed analysis of LOH on chromosome band 17p13 in breast carcinoma on the basis of a high-resolution physical map with 29 markers. Genes Chromosomes Cancer 9: 173–179.

    Article  CAS  Google Scholar 

  • Knudson, A. G. (1985). Hereditary cancer, oncogenes and antioncogenes. Cancer Res 45: 1437–1443.

    CAS  PubMed  Google Scholar 

  • Lancaster, J. M., Wooster, R., Mangion, J., Phelan, C. M., Cochran, C., Gumbs, C., Seal, S., Barfoot, R., Collins, N., Bignell, G., Patel, S., Hamoudi, R., Larsson, C., Wiseman, R. W., Berchuck, A., lglehart, J. D., Marks, J. R., Ashworth, A., Stratton, M. R. & Futreal, P. A. (1996). BRCA2 mutations in primary breast and ovarian cancers. Nat Genet 13: 238–240.

    Article  CAS  Google Scholar 

  • Lindblom, A., Skoog, L., Andersen, T. I., Rotstein, S., Nordenskjold, M. & Larsson, C. (1993). Four separate regions on chromosome 17 show loss of heterozygosity in familial breast carcinomas. Hum Genet 91: 6–12.

    Article  CAS  Google Scholar 

  • Mackay, J., Steel, C. M., Elder, P. A., Forrest, A. P. & Evans, H. J. (1988). Allele loss on short arm of chromosome 17 in breast cancers. Lancet ii: 1384–1385.

    Article  Google Scholar 

  • Makos, M., Biel, M. A., Deiry, W. E., Nelkin, B. D., Issa, J. P., Cavenee, W. K., Kuerbitz, S. J. & Baylin, S. B. (1995). p53 activates expression of HIC-1, a new candidate tumour suppressor gene on 17p13.3. Nature Med 1: 570–577.

    Article  Google Scholar 

  • Merlo, G. R., Venesio, T., Bernardi, A., Cropp, C. S., Diella, F., Cappa, A. P. M., Callahan, R. & Liscia, D. S. (1994). Evidence for a second tumour suppressor gene on chromosome 17p linked to high S-phase index in primary human breast carcinomas. Cancer Genet Cytogenet 76: 106–111.

    Article  CAS  Google Scholar 

  • Meroni, G., Reymond, A., Alcalay, M., Borsani, G., Tanigami, A., Tonlorenzi, R., Lo Nigro, C., Messali, S., Zollo, M., Ledbetter, D. H., Brent, R., Ballabio, A. & Carrozzo, R. (1997). Rox, a novel bHLHZip protein expressed in quiescent cells that heterodimerizes with Max, binds a non-canonical E Box and acts as a transcriptional repressor. EMBO J 16: 2892–2906.

    Article  CAS  Google Scholar 

  • Milner, J. & Medcalf, E. A. (1991). Cotranslation of activated mutant p53 with wild type drives the wild type p53 protein into the mutant conformation. Cell 65: 765–774.

    Article  CAS  Google Scholar 

  • Mittra, I. & MacRae, K. D. (1991). A meta-analysis of reported correlations between prognostic factors in breast cancer: does axillary lymph node metastasis represent biology or chronology?. Eur J Cancer 27: 1574–1583.

    Article  CAS  Google Scholar 

  • Morris, C., Benjes, S., Haataja, L., Ledbetter, D. H., Heisterkamp, N. & Groffen, J. (1995). Spatial organization of ABR and CRK genes on human chromosome band 17p13.3. Oncogene 10: 1009–1011.

    CAS  PubMed  Google Scholar 

  • Nagai, M. A., Pacheco, M. M., Brentani, M. M., Marques, L. A., Brentani, R. R., Ponder, B. A. & Mulligan, L. M. (1994). Allelic loss on distal chromosomes 17p is associated with poor prognosis in a group of Brazilian breast-cancer patients. Br J Cancer 69: 754–758.

    Article  CAS  Google Scholar 

  • Nakamura, Y., Ballard, L., Leppert, M., O’Connel, P., Lathrop, G. M., Lalouel, J. M. & White, R. (1988). Isolation and mapping of a polymorphic DNA sequence (pYNZ22) on chromosome 17p [D17S30]. Nucleic Acids Res 16: 570–.

    Google Scholar 

  • Neuhausen, S. L. & Marshall, C. J. (1994). Loss of heterozygosity in familial tumors from three BRCA1-linked kindreds. Cancer Res 54: 6069–6072.

    CAS  PubMed  Google Scholar 

  • Radford, D. M., Fair, K. L., Phillips, N. J., Ritter, J. H., Steinbrueck, T., Holt, M. S. & Donis-Keller, H. (1995). Allelotyping of ductal carcinoma in situ of the breast: deletion of loci on 8p, 13q, 16q, 17p and 17q. Cancer Res 55: 3399–3405.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Schultz, D. C., Vanderveer, L., Berman, D. B., Hamilton, T. C., Wong, A. J. & Godwin, A. K. (1996). Identification of two candidate tumor suppressor genes on chromosome 17p13.3. Cancer Res 56: 1997–2002.

    CAS  PubMed  Google Scholar 

  • Sidransky, D., Takashi, T., Helzlsouer, K., Zehnbauer, B., Rausch, G., Shelton, B., Prestigiacomo, L., Vogelstein, B. & Davidson, N. (1992). Inherited p53 gene mutations in breast cancer. Cancer Res 52: 2984–2986.

    CAS  PubMed  Google Scholar 

  • Sjögren, S., Inganas, M., Norberg, T., Lindgren, A., Nordgren, H., Holmberg, L. & Bergh, J. (1996). The p53 gene in breast cancer: prognostic value of complementary DNA sequencing versus immunohistochemistry. J Natl Cancer Inst 88: 173–182.

    Article  Google Scholar 

  • Stack, M., Jones, D., White, G., Liscia, D. S., Venesio, T., Casey, G., Crichton, D., Varley, J., Mitchell, E., Heighway, J. & Santibanez-Koref, M. (1995). Detailed mapping and loss of heterozygosity analysis suggests a suppressor locus involved in sporadic breast cancer within a distal region of chromosome band 17. Hum Mol Genet 4: 2047–2055.

    Article  CAS  Google Scholar 

  • Theile, M., Hartmann, S., Scherthan, H., Arnold, W., Deppert, W., Frege, R., Glaab, F., Haensch, W. & Scherneck, S. (1995). Suppression of tumorigenicity of breast cancer cells by transfer of human chromosome 17 does not require transferred BRCA1 and p53 genes. Oncogene 10: 439–447.

    CAS  PubMed  Google Scholar 

  • White, G. R. M., Stack, M., Santibanez-Koref, M., Liscia, D. S., Venesio, T., Wang, J. C., Helms, C., Donis-Keller, H., Betticher, D. C., Altermatt, H. J., Hoban, P. R. & Heighway, J. (1996). High levels of loss at the 17p telomere suggest the close proximity of a tumour suppressor. J Cancer 74: 863–870.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Dipartimento Oncologico ASL-1, Servizio di Anatomia Patologica, via Cavour 31, Torino, 10123, CAP, Italy

    D S Liscia, R Morizio, T Venesio, C Palenzona & M Donadio

  2. Oncogenetic Section, LTIB, National Cancer Institute, Bethesda, MD, USA

    R Callahan

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  1. D S Liscia
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  2. R Morizio
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From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/

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Cite this article

Liscia, D., Morizio, R., Venesio, T. et al. Prognostic significance of loss of heterozygosity at loci on chromosome 17p13.3-ter in sporadic breast cancer is evidence for a putative tumour suppressor gene. Br J Cancer 80, 821–826 (1999). https://doi.org/10.1038/sj.bjc.6690427

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  • Received: 11 November 1998

  • Accepted: 09 December 1998

  • Published: 23 April 1999

  • Issue date: 01 May 1999

  • DOI: https://doi.org/10.1038/sj.bjc.6690427

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Keywords

  • breast cancer
  • chromosome 17p13.3
  • LOH
  • survival

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