Genetic changes in breast carcinomas in an Icelandic population.
We have examined breast tumour samples from 109 unselected breast cancer patients for genetic changes on chromosomes 13 and 17. We have looked for allelic losses, firstly, at the retinoblastoma locus, RB1, on chromosome 13q, and secondly, on both arms of chromosome 17. We have also studied the same samples for amplification of the erbB2 oncogene. We searched for mutations in four well conserved areas of the p53 gene using constant denaturant gradient electrophoresis (CDGE). Allelic loss or rearrangement was detected in a large proportion of the tumours, affecting 37-51% of cases with different probes. The areas most frequently affected were 17p13.1 and 17p13.3. Point mutations and small deletions in the p53 gene on 17p13.1 were detected in 16% of the tumours. The data on genetic changes were then analyzed for three different correlations: 1) co-operation between different lesions, 2) association with family history of breast cancer, 3) correlation with clinical factors and prognosis. There was association between losses at the retinoblastoma locus and losses on 17p and 17q. We also found an association between p53 mutations and amplification of the erbB2 oncogene. Relatives of patients having deletions at the retinoblastoma locus and/or sites on chromosome 17 in the tumours have a significantly increased relative risk of developing breast cancer. No such correlation is found for p53 mutations or erbB2 amplification. No p53 germline mutations were detected. P53 mutations do, however, appear to be a strong indication of poor prognosis in this population.
Eyfjörd
J E
JE
Molecular and Cell Biology Laboratory, Icelandic Cancer Society, Reykjavik.
Thorlacius
S
S
D000483:Alleles; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D002869:Chromosome Aberrations; D002882:Chromosomes, Human, Pair 13; D002886:Chromosomes, Human, Pair 17; D004252:DNA Mutational Analysis; D005260:Female; D005784:Gene Amplification; D016161:Genes, Retinoblastoma; D016158:Genes, p53; D006801:Humans; D007055:Iceland / Q000453:epidemiology; D009857:Oncogenes; D011379:Prognosis