title: Loss of heterozygosity and microsatellite instability at chromosomal sites 1Q and 10Q in morphologically distinct regions of late stage prostate lesions.
abstract: OBJECTIVE
  We investigated the incidence of loss of heterozygosity (LOH) and microsatellite instability in sporadic prostate cancer and surrounding tissue at loci encompassing the HPC1 and PTEN genes.
  
  
  METHODS
  Surgical specimens from 63 patients with sporadic stage T3 or T4 prostatic adenocarcinoma were analyzed for LOH and microsatellite instability. Microdissected tissue included morphologically normal foci, benign prostatic hyperplasia (BPH) and prostatic adenocarcinoma. LOH analysis was performed using 4 microsatellite markers that map in the region of the 1q24 to 25 locus of the putative prostate cancer susceptibility gene HPC1 and 4 that map in the region of the 10q23 locus of the PTEN gene.
  
  
  RESULTS
  The incidence of LOH on 10q was consistent with that previously reported in prostatic tumors. LOH associated with the PTEN locus was recorded in morphologically normal foci, BPH and adenocarcinoma. Sequence analysis of PTEN in a limited number of lesions revealed mutations in nontumor and tumor tissue. Analysis of the DS10215 locus showed significant LOH in tumor but not in benign tissue, suggestive of a tumor suppressor gene in this region associated with prostatic neoplastic progression. In contrast, no significant LOH was observed in the same tissues at 4 loci on chromosome 1q. In this study we recorded elevated levels of microsatellite instability in benign prostatic tissue with an additional increase associated with prostatic adenocarcinoma.
  
  
  CONCLUSIONS
  The low incidence of LOH in the region of the HPC1 locus in all prostate lesions studied suggests that this putative hereditary prostate cancer susceptibility locus does not appear to have a role in sporadic prostate cancer, at least not in the context of LOH. In contrast, analysis of the same tissues for LOH at chromosome 10q confirmed frequent alterations in this region linked to late stage prostate cancer. PTEN mutations in microdissected morphologically normal and BPH tissue showed alterations in nontumor tissue surrounding adenocarcinoma. Microsatellite instability was increased in adenocarcinomas over an elevated background recorded in surrounding tissues.
authors.affiliation: Department of Urology, Lahey Clinic, Burlington, Massachusetts, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Latini
authors.forename: K M
authors.initials: KM
authors.lastname: Rieger-Christ
authors.forename: D S
authors.initials: DS
authors.lastname: Wang
authors.forename: M L
authors.initials: ML
authors.lastname: Silverman
authors.forename: J A
authors.initials: JA
authors.lastname: Libertino
authors.forename: I C
authors.initials: IC
authors.lastname: Summerhayes
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000954:Antigens, Surface / Q000235:genetics; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009367:Neoplasm Staging; D009419:Nerve Tissue Proteins / Q000235:genetics; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics; D017354:Point Mutation; D011470:Prostatic Hyperplasia / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D050827:Syntaxin 1; D025521:Tumor Suppressor Proteins
chemical_list: D000954:Antigens, Surface; D009419:Nerve Tissue Proteins; D050827:Syntaxin 1; D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human