PMID- 17350463 OWN - NLM STAT- MEDLINE DCOM- 20070411 LR - 20101118 IS - 0165-4608 (Print) IS - 0165-4608 (Linking) VI - 174 IP - 1 DP - 2007 Apr 1 TI - Haploinsufficiency of 8p22 may influence cancer-specific survival in prostate cancer. PG - 24-34 AB - 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. FAU - Matsuyama, Hideyasu AU - Matsuyama H AD - Department of Urology, Yamaguchi University School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan. FAU - Oba, Kazuo AU - Oba K FAU - Matsuda, Kenji AU - Matsuda K FAU - Yoshihiro, Satoru AU - Yoshihiro S FAU - Tsukamoto, Manabu AU - Tsukamoto M FAU - Kinjo, Mitsuru AU - Kinjo M FAU - Sagiyama, Kazuyuki AU - Sagiyama K FAU - Takei, Mineo AU - Takei M FAU - Yamaguchi, Akito AU - Yamaguchi A FAU - Sasaki, Kohsuke AU - Sasaki K FAU - Naito, Katsusuke AU - Naito K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Cancer Genet Cytogenet JT - Cancer genetics and cytogenetics JID - 7909240 SB - IM MH - Aged MH - Aged, 80 and over MH - Chromosomes, Human, Pair 8/*genetics MH - Gene Dosage/*genetics MH - Genome, Human/genetics MH - Haploidy MH - Humans MH - In Situ Hybridization, Fluorescence MH - Kaplan-Meier Estimate MH - Loss of Heterozygosity/genetics MH - Male MH - Metaphase MH - Middle Aged MH - Neoplasm Staging MH - Prognosis MH - Proportional Hazards Models MH - Prostate/pathology MH - Prostatic Neoplasms/*genetics/pathology MH - Survival Analysis MH - Treatment Outcome EDAT- 2007/03/14 09:00 MHDA- 2007/04/12 09:00 CRDT- 2007/03/14 09:00 PHST- 2006/09/01 00:00 [received] PHST- 2006/10/30 00:00 [revised] PHST- 2006/11/03 00:00 [accepted] PHST- 2007/03/14 09:00 [pubmed] PHST- 2007/04/12 09:00 [medline] PHST- 2007/03/14 09:00 [entrez] AID - S0165-4608(06)00735-7 [pii] AID - 10.1016/j.cancergencyto.2006.11.008 [doi] PST - ppublish SO - Cancer Genet Cytogenet. 2007 Apr 1;174(1):24-34. doi: 10.1016/j.cancergencyto.2006.11.008.