Evidence for a second tumor suppressor gene on 17p linked to high S-phase index in primary human breast carcinomas.
The short area of chromosome 17 is a frequent target for deletions in human tumors, including breast cancer. We have investigated by restriction fragment polymorphism analysis the pattern of loss of heterozygosity (LOH) at four loci on 17p13.1-17pter in a panel of 110 primary human breast carcinomas. A copy of the p53 gene was lost in 23% of the informative cases. Point mutations in the p53 gene were statistically associated with LOH at the same locus (p = 0.003) but not at other loci on 17p13.3-17pter. A second region bordered by the loci D17S5/D17S28 (17p13.3) and D17S34 (17pter) is also affected by LOH, independent of point mutations in the p53 gene. We propose the presence of a second tumor suppressor gene within this region. In support of this hypothesis is the significant association (p = 0.005) between LOH at the D17S5/D17S28, but not at the TP53 or D17S34 loci, and tumors having a high S-phase index.
Merlo
G R
GR
Oncogenetics Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Venesio
T
T
Bernardi
A
A
Cropp
C S
CS
Diella
F
F
Cappa
A P
AP
Callahan
R
R
Liscia
D S
DS
D000483:Alleles; D001943:Breast Neoplasms / Q000235:genetics*; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D016158:Genes, p53; D006579:Heterozygote; D006801:Humans; D017354:Point Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D016196:S Phase / Q000235:genetics*