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.
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.
Liscia
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Dipartimento Oncologico ASL-1, Torino, Italy.
Morizio
R
R
Venesio
T
T
Palenzona
C
C
Donadio
M
M
Callahan
R
R
D000483:Alleles; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000097:blood / Q000235:genetics* / Q000473:pathology; D002886:Chromosomes, Human, Pair 17; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D016147:Genes, Tumor Suppressor; D016158:Genes, p53; D006801:Humans; D019656:Loss of Heterozygosity; D015999:Multivariate Analysis; D010641:Phenotype; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011379:Prognosis; D016019:Survival Analysis
D004273:DNA, Neoplasm