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Preproenkephalin hypermethylation in the pure pancreatic juice compared with p53 mutation in the diagnosis of pancreatic carcinoma.
J Gastroenterol. 2006 Aug; 41(8):791-7.JG

Abstract

BACKGROUND

Aberrant methylation of CpG islands is a common mechanism for the dysregulation of tumor suppressor genes in a variety of human malignancies. Preproenkephalin ppENK) hypermethylation is recognized in 90% of pancreatic carcinoma (PCa) tissues, but not in normal pancreas. We analyzed ppENK hypermethylation in pure pancreatic juice (PPJ) in patients with PCa, intraductal papillary mucinous neoplasms (IPMN), and chronic pancreatitis (CP), and elucidated its usefulness as a marker in the diagnosis of PCa compared with p53 mutation.

METHODS

PPJ was collected endoscopically from 28 patients with PCa, 15 patients with IPMN, and 20 patients with CP. DNA was extracted from the supernatant and the sediment of PPJ. Methylation-specific polymerase chain reaction was performed for hypermethylation analysis of ppENK. In addition, single-strand conformation polymorphism and direct sequencing were performed simultaneously to identify p53 mutations.

RESULTS

The incidence of ppENK hypermethylation in the supernatant and/or the sediment of PPJ was 50% (14 of 28) in patients with PCa. In contrast, the incidence of ppENK hypermethylation was 26.7% (4 of 15) in patients with IPMN, and 5% (1 of 20) in patients with CP (P < 0.002). The incidence of p53 mutations in the PPJ was 42.9% (12 of 28) in patients with PCa and 0% (0 of 20) in patients with CP. Furthermore, the incidence of ppENK hypermethylation and/or p53 mutations in the PPJ was enhanced to 67.9% (19 of 28) in patients with PCa in the combination assay.

CONCLUSIONS

These results suggest that ppENK hypermethylation in PPJ is specific for cancer, and the combination assay with p53 enhances the genetic diagnosis of PCa.

Authors+Show Affiliations

Department of Internal Medicine and Medical Oncology, Cancer Research Institute, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

16988769

Citation

Ohtsubo, Koushiro, et al. "Preproenkephalin Hypermethylation in the Pure Pancreatic Juice Compared With P53 Mutation in the Diagnosis of Pancreatic Carcinoma." Journal of Gastroenterology, vol. 41, no. 8, 2006, pp. 791-7.
Ohtsubo K, Watanabe H, Yao F, et al. Preproenkephalin hypermethylation in the pure pancreatic juice compared with p53 mutation in the diagnosis of pancreatic carcinoma. J Gastroenterol. 2006;41(8):791-7.
Ohtsubo, K., Watanabe, H., Yao, F., Okada, G., Mouri, H., Yamaguchi, Y., & Sawabu, N. (2006). Preproenkephalin hypermethylation in the pure pancreatic juice compared with p53 mutation in the diagnosis of pancreatic carcinoma. Journal of Gastroenterology, 41(8), 791-7.
Ohtsubo K, et al. Preproenkephalin Hypermethylation in the Pure Pancreatic Juice Compared With P53 Mutation in the Diagnosis of Pancreatic Carcinoma. J Gastroenterol. 2006;41(8):791-7. PubMed PMID: 16988769.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Preproenkephalin hypermethylation in the pure pancreatic juice compared with p53 mutation in the diagnosis of pancreatic carcinoma. AU - Ohtsubo,Koushiro, AU - Watanabe,Hiroyuki, AU - Yao,Fan, AU - Okada,Gensaku, AU - Mouri,Hisatsugu, AU - Yamaguchi,Yasushi, AU - Sawabu,Norio, PY - 2006/03/14/received PY - 2006/05/22/accepted PY - 2006/9/22/pubmed PY - 2006/12/28/medline PY - 2006/9/22/entrez SP - 791 EP - 7 JF - Journal of gastroenterology JO - J. Gastroenterol. VL - 41 IS - 8 N2 - BACKGROUND: Aberrant methylation of CpG islands is a common mechanism for the dysregulation of tumor suppressor genes in a variety of human malignancies. Preproenkephalin ppENK) hypermethylation is recognized in 90% of pancreatic carcinoma (PCa) tissues, but not in normal pancreas. We analyzed ppENK hypermethylation in pure pancreatic juice (PPJ) in patients with PCa, intraductal papillary mucinous neoplasms (IPMN), and chronic pancreatitis (CP), and elucidated its usefulness as a marker in the diagnosis of PCa compared with p53 mutation. METHODS: PPJ was collected endoscopically from 28 patients with PCa, 15 patients with IPMN, and 20 patients with CP. DNA was extracted from the supernatant and the sediment of PPJ. Methylation-specific polymerase chain reaction was performed for hypermethylation analysis of ppENK. In addition, single-strand conformation polymorphism and direct sequencing were performed simultaneously to identify p53 mutations. RESULTS: The incidence of ppENK hypermethylation in the supernatant and/or the sediment of PPJ was 50% (14 of 28) in patients with PCa. In contrast, the incidence of ppENK hypermethylation was 26.7% (4 of 15) in patients with IPMN, and 5% (1 of 20) in patients with CP (P < 0.002). The incidence of p53 mutations in the PPJ was 42.9% (12 of 28) in patients with PCa and 0% (0 of 20) in patients with CP. Furthermore, the incidence of ppENK hypermethylation and/or p53 mutations in the PPJ was enhanced to 67.9% (19 of 28) in patients with PCa in the combination assay. CONCLUSIONS: These results suggest that ppENK hypermethylation in PPJ is specific for cancer, and the combination assay with p53 enhances the genetic diagnosis of PCa. SN - 0944-1174 UR - https://www.unboundmedicine.com/medline/citation/16988769/Preproenkephalin_hypermethylation_in_the_pure_pancreatic_juice_compared_with_p53_mutation_in_the_diagnosis_of_pancreatic_carcinoma_ L2 - https://dx.doi.org/10.1007/s00535-006-1857-3 DB - PRIME DP - Unbound Medicine ER -