TY - JOUR
T1 - 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
AU - Liscia, D. S.
AU - Morizio, R.
AU - Venesio, T.
AU - Palenzona, C.
AU - Donadio, M.
AU - Callahan, R.
PY - 1999
Y1 - 1999
N2 - 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.
AB - 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.
KW - Breast cancer
KW - Chromosome 17p13.3
KW - LOH
KW - Survival
UR - http://www.scopus.com/inward/record.url?scp=0032941268&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032941268&partnerID=8YFLogxK
U2 - 10.1038/sj.bjc.6690427
DO - 10.1038/sj.bjc.6690427
M3 - Article
C2 - 10360661
AN - SCOPUS:0032941268
VL - 80
SP - 821
EP - 826
JO - British Journal of Cancer
JF - British Journal of Cancer
SN - 0007-0920
IS - 5-6
ER -