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. 1999 May;80(5-6):821-6. doi: 10.1038/sj.bjc.6690427.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Breast Neoplasms / blood
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Carcinoma, Ductal, Breast / blood
  • Carcinoma, Ductal, Breast / genetics*
  • Carcinoma, Ductal, Breast / pathology
  • Chromosomes, Human, Pair 17*
  • DNA, Neoplasm / genetics
  • Female
  • Genes, Tumor Suppressor*
  • Genes, p53
  • Humans
  • Loss of Heterozygosity*
  • Multivariate Analysis
  • Phenotype
  • Point Mutation
  • Polymerase Chain Reaction
  • Prognosis
  • Survival Analysis

Substances

  • DNA, Neoplasm