title: Mapping of genetic deletions on chromosome 3 in colorectal cancer: loss of 3p25-pter is associated with distant metastasis and poor survival.
abstract: OBJECTIVE
  There is no detailed analysis of loss of heterozygosity (LOH) on chromosome 3 in colorectal cancer (CRC). Our aim was to define frequently deleted loci on chromosome 3 and to explore novel prognostic markers and the locations of candidate tumor suppressor genes associated with CRC.
  
  
  METHODS
  LOH at 23 microsatellite markers spanning on chromosome 3 was determined in 112 sporadic CRC by automated fluorescence-based polymerase chain reaction. Genetic loss was assessed for the clinicopathological significance by univariate and multivariate analyses.
  
  
  RESULTS
  Fifty-eight (51.8%) of 112 carcinomas exhibited LOH at one or more loci tested. Among seven loci with high LOH rates, allelic losses at D3S1297 and D3S1266 occurred more frequently in younger patients. A marked gender distortion for genetic deletion was observed at six loci, where LOH was identified more frequently in male cases. For clinical outcome, LOH solely at D3S1297 (3p26.3) was significantly associated with distant metastasis (P = 0.001) and was indicative of a shorter overall survival (P = 0.014). In addition, loss of one common deletion region at 3p25-pter was significantly correlated to distant metastasis (P = 0.009) and had an adverse effect on patients' overall survival in univariate and multivariate tests (P = 0.009 and 0.001, respectively).
  
  
  CONCLUSIONS
  Loss of chromosome 3p25-pter could act as an independent predicator of poor prognosis in CRC, suggesting that microsatellite analysis is a useful means to stratify patients into different risk groups. In addition, inactivation of candidate tumor suppressor genes in this region might involve in CRC progression.
authors.affiliation: School of Medicine, Fu-Jen Catholic University, Taipei, Taiwan.
authors.forename: Ming-Hong
authors.initials: MH
authors.lastname: Tsai
authors.forename: Woei-Horng
authors.initials: WH
authors.lastname: Fang
authors.forename: Shu-Hwa
authors.initials: SH
authors.lastname: Lin
authors.forename: Sheng-Tai
authors.initials: ST
authors.lastname: Tzeng
authors.forename: Chen-Syuan
authors.initials: CS
authors.lastname: Huang
authors.forename: Sou-Jhy
authors.initials: SJ
authors.lastname: Yen
authors.forename: Shao-Jiun
authors.initials: SJ
authors.lastname: Chou
authors.forename: Ya-Chien
authors.initials: YC
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000556:secondary; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011379:Prognosis; D017384:Sequence Deletion; D015996:Survival Rate
chemical_list: D004273:DNA, Neoplasm