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Author: Suzuki, H.; Emi, M.; Komiya, A.; Fujiwara, Y.; Yatani, R.; Nakamura,
Y.; Shimazaki, J.
Year: 1995
Title: Localization of a tumor suppressor gene associated with progression
of human prostate cancer within a 1.2 Mb region of 8p22-p21.3
Journal: Genes Chromosomes Cancer
Volume: 13
Issue: 3
Pages: 168-74
Label: 95399363
Keywords: Adenocarcinoma/*genetics
Chromosome Mapping
*Chromosomes, Human, Pair 8
DNA, Neoplasm/analysis
Gene Deletion
Genes, Suppressor, Tumor/*genetics
Human
Male
Prostatic Neoplasms/*genetics
Support, Non-U.S. Gov't
Abstract: Human prostate cancers frequently show loss of heterozygosity
at loci on the short arm of chromosome 8. In order to take a step
toward isolation of the putative tumor suppressor gene(s) on 8p
via positional cloning, we performed high-resolution deletion
mapping in 46 prostate cancers (stage B, 20 cases; stage C, 8
cases; endocrine therapy- resistant cancer death, 18 cases) using
new 12 restriction fragment length polymorphism markers for this
chromosomal region. Allelic losses were observed in 25 of the
44 cases (57%) that were informative with at least one locus.
Detailed deletion mapping defined a 1.2 Mb commonly deleted region
at 8p22-p21.3 flanked by markers cMSR-32 and C18-1051. A second
region of common deletion was identified between C18-1312 and
C18-494 at 8p21-8p11.22, suggesting that at least two tumor suppressor
genes associated with prostate cancer are present on chromosome
arm 8p. Allelic losses on 8p were observed more frequently in
the cancer death cases (14/17, 82%) than in early-stage tumors
(11/27, 40%; P 0.01, Fisher's exact test). In two out of 7 patients
for whom DNA was available from metastatic cancers as well as
from normal tissues and primary tumors, the primary cancer foci
had no detectable abnormality of 8p, but the metastatic tumors
showed loss of heterozygosity. These results suggest that inactivation
of tumor suppressor genes on 8p plays an important role in the
progression of prostate cancer.