title: Haploinsufficiency of 8p22 may influence cancer-specific survival in prostate cancer.
abstract: Although Knudson's two-hit hypothesis with functional loss of a tumor suppressor gene has been widely accepted, accumulating evidence suggests that several genes are regulated by the quantity of their product in a dose-dependent manner (gene dosage effect). The study was designed to identify the influence of gene dosage effect of 8p22 on patient prognosis. With a median age of 71 years, 40 patients with prostate cancer (11 organ-confined, 13 capsular penetrating, and 16 nodal and/or distant metastatic) were followed for a median of 68.5 months. A fluorescence in situ hybridization (FISH) technique was applied using a region-specific cosmid probe combined with centromeric probe. Allelic losses of 8p22, 8p21.3, 8p21.1 approximately 2, and 8p12 were found in 23, 22, 14, and 9 patients, respectively. A Cox proportional hazard model revealed that decreased fraction (i.e., the fraction of nuclei with a lesser number of cosmid signals than of centromeric probe signals) of 8p22 proved to be the sole independent prognostic factor predicting cancer-specific death, as well as disease progression--but allelic loss of 8p22 was not predictive. Cytogenetic estimation of 8p22 by FISH can yield quantitative evaluation of relevant gene dosage, which may become a useful biomolecular marker predicting poor patient prognosis.
authors.affiliation: Department of Urology, Yamaguchi University School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.
authors.forename: Hideyasu
authors.initials: H
authors.lastname: Matsuyama
authors.forename: Kazuo
authors.initials: K
authors.lastname: Oba
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsuda
authors.forename: Satoru
authors.initials: S
authors.lastname: Yoshihiro
authors.forename: Manabu
authors.initials: M
authors.lastname: Tsukamoto
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Kinjo
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Sagiyama
authors.forename: Mineo
authors.initials: M
authors.lastname: Takei
authors.forename: Akito
authors.initials: A
authors.lastname: Yamaguchi
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Sasaki
authors.forename: Katsusuke
authors.initials: K
authors.lastname: Naito
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D018628:Gene Dosage / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics; D006238:Haploidy; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D008677:Metaphase; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D011467:Prostate / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D016019:Survival Analysis; D016896:Treatment Outcome