Aberrant methylation of Reprimo correlates with genetic instability and predicts poor prognosis in pancreatic ductal adenocarcinoma.
Publication/Presentation Date
7-15-2006
Abstract
BACKGROUND: The p53-dependent G2/M checkpoint plays a key role in the maintenance of genomic integrity, thereby protecting cells from neoplastic progression. Reprimo, a gene involved in the p53-induced G2 cell cycle arrest, has been recently identified as a novel target for aberrant methylation in pancreatic and other cancers. The biological and clinical relevance of Reprimo methylation in pancreatic cancer was investigated.
METHODS: The methylation status of Reprimo CpG island was analyzed by methylation-specific polymerase chain reaction in a large series of pancreatic cancers and was correlated with p53 mutation status, genetic instability (as measured by the fractional allelic loss), and clinicopathologic features.
RESULTS: Aberrant methylation of Reprimo was identified in 60% (75 of 125) of pancreatic cancer xenografts and primary pancreatic adenocarcinomas. Reprimo methylation was also detectable in 30% (19 of 63) of pancreatic intraepithelial neoplasias (PanIN), known precursors to infiltrating carcinoma. Reprimo methylation was unrelated to the p53 mutation status and associated with the increased degree of genetic instability (P = .04). Furthermore, we found that patients with Reprimo methylation in their primary pancreatic cancers have significantly worse prognosis than those without Reprimo methylation (P = .007). In contrast, other methylation targets in pancreatic cancers (SPARC and CXCR4) did not correlate with prognosis.
CONCLUSIONS: These results suggest that aberrant methylation of Reprimo is a common event in pancreatic carcinogenesis and is associated with genetic instability and unfavorable outcome after surgical resection.
Volume
107
Issue
2
First Page
251
Last Page
257
ISSN
0008-543X
Published In/Presented At
Sato, N., Fukushima, N., Matsubayashi, H., Iacobuzio-Donahue, C. A., Yeo, C. J., & Goggins, M. (2006). Aberrant methylation of Reprimo correlates with genetic instability and predicts poor prognosis in pancreatic ductal adenocarcinoma. Cancer, 107(2), 251–257. https://doi.org/10.1002/cncr.21977
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
16752411
Department(s)
Administration and Leadership
Document Type
Article