Loss of 18q22.3 involving the carboxypeptidase of glutamate-like gene is associated with poor prognosis in resected pancreatic cancer

Clin Cancer Res. 2012 Jan 15;18(2):524-33. doi: 10.1158/1078-0432.CCR-11-1903. Epub 2011 Nov 29.


Purposes: Pancreatic cancer is the fourth leading cause of cancer-related death, and studies on the clinical relevance of its genomic imbalances are warranted.

Experimental design: Recurrent copy number alterations of cytobands and genes were analyzed by array comparative genomic hybridization (aCGH) in 44 resected pancreatic cancer specimens. Prognostic markers identified by aCGH were validated by PCR gene copy number assay in an independent validation cohort of 61 resected pancreatic cancers. The functions of gene identified were evaluated by proliferation, cell cycle, and migration assays in pancreatic cancer cells.

Results: We showed recurrent copy number gains and losses in the first cohort. Loss of 18q22.3 was significantly associated with short-term overall survival in the first cohort (P = 0.019). This cytoband includes the carboxypeptidase of glutamate-like (CPGL) gene. CPGL gene deletion was associated with shorter overall survival in the validation cohort (P = 0.003). CPGL deletion and mutations of TP53 or Kras seem to be independent events. A Cox model analysis of the two cohorts combined showed that loss of 18q22.3/deletion of the CPGL gene was an independent poor prognostic factor for overall survival (HR = 2.72, P = 0.0007). Reconstitution of CPGL or its splicing variant CPGL-B into CPGL-negative pancreatic cancer cells attenuated cell growth, migration, and induced G(1) accumulation.

Conclusion: Loss of 18q22.3/deletion of the CPGL gene is a poor prognostic marker in resected pancreatic cancer, and functional studies suggest the CPGL gene as growth suppressor gene in pancreatic cancer.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Carcinoma, Pancreatic Ductal / genetics*
  • Carcinoma, Pancreatic Ductal / mortality
  • Carcinoma, Pancreatic Ductal / surgery
  • Cell Line, Tumor
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 18 / genetics*
  • Cohort Studies
  • Comparative Genomic Hybridization
  • DNA Copy Number Variations
  • DNA Mutational Analysis
  • Dipeptidases / genetics*
  • Dipeptidases / metabolism
  • Disease-Free Survival
  • Female
  • Genes, Tumor Suppressor
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / surgery
  • Prognosis
  • Proportional Hazards Models
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins p21(ras)
  • Tumor Suppressor Protein p53 / genetics
  • ras Proteins / genetics


  • KRAS protein, human
  • Proto-Oncogene Proteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Dipeptidases
  • CNDP2 protein, human
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins