Distal deletion of chromosome Ip in ductal carcinoma of the breast.
By use of recombinant DNA probes that correspond to genetic loci residing on human chromosome 1, DNA samples from 37 ductal breast carcinomas and constitutional DNA from the same individuals were tested for loss of heterozygosity. A high frequency (41%) of reduction to homozygosity was detected with the probe p1-79, which recognizes the highly polymorphic locus D1Z2, localized on 1p36. Loss of heterozygosity at other chromosome 1 loci was much less common, not exceeding a frequency of 10%, and was never observed in the absence of the D1Z2 loss. Somatic loss of heterozygosity at D1Z2 was more frequent in patients with a strong family history of breast cancer (60%), in patients with early diagnosis (before 45 years of age) (70%), and in those with multiple tumors or tumor foci (50%) than in patients with none of the characteristics of hereditary tumors (21%). No associations were observed between loss of heterozygosity and prognostic factors. These results suggest that inactivation of a tumor suppressor gene located on the distal portion of chromosome 1p, alone or combined with other genetic changes, may represent a fundamental step in the pathogenesis of ductal carcinoma of the breast.
Genuardi
M
M
Department of Biochemistry and Molecular Biology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Tsihira
H
H
Anderson
D E
DE
Saunders
G F
GF
D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics*; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged
D004273:DNA, Neoplasm