Allelic loss on distal chromosome 17p is associated with poor prognosis in a group of Brazilian breast cancer patients.
We examined loss of heterozygosity (LOH) for two loci on chromosome 17p (D17S5 and TP53), and erbB-2 gene amplification, in primary breast cancers from 67 Brazilian patients. We identified two distinct regions of LOH on chromosome 17p, one spanning TP53 and the other a more telomeric region (D17S5). Based on a short-term follow-up, Kaplan-Meier analyses of patients' disease-free survival showed that patients with LOH for D17S5, but retaining heterozygosity for TP53, were at higher risk of recurrence (P = 0.007) than those who retained heterozygosity for D17S5. Bivariate analyses indicated that patients with LOH for D17S5 alone had an increased risk of recurrence (hazard ratio = 7.2) over patients with erbB-2 amplification (hazard ratio = 3.7), when compared with patients with neither alteration (hazard ratio = 1.0). Further, lymph node-positive patients whose tumours had both LOH for D17S5 and erbB-2 gene amplification had a higher risk of recurrence than patients whose tumours had neither of these genetic alterations. Our data confirm previous reports of a putative tumour-suppressor gene, distinct from TP53, on distal chromosome 17p which is associated with breast cancer. They further suggest that LOH for loci in this region may provide an independent indicator to identify patients with poor prognosis.
Nagai
M A
MA
Faculdade de Medicina, Universidade de São Paulo, Brazil.
Pacheco
M M
MM
Brentani
M M
MM
Marques
L A
LA
Brentani
R R
RR
Ponder
B A
BA
Mulligan
L M
LM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001938:Brazil / Q000453:epidemiology; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000401:mortality; D018275:Carcinoma, Lobular / Q000235:genetics / Q000401:mortality; D018276:Carcinoma, Medullary / Q000235:genetics / Q000401:mortality; D002886:Chromosomes, Human, Pair 17; D004273:DNA, Neoplasm / Q000032:analysis; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D016158:Genes, p53; D006579:Heterozygote; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D016016:Proportional Hazards Models; D011518:Proto-Oncogene Proteins / Q000235:genetics; D011519:Proto-Oncogenes / Q000235:genetics*; D018719:Erb-b2 Receptor Tyrosine Kinases; D012307:Risk Factors; D016019:Survival Analysis; D016615:Telomere / Q000473:pathology
D004273:DNA, Neoplasm; D066246:ErbB Receptors; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases