Identification and characterization of differentially methylated CpG islands in pancreatic carcinoma.

Abstract:

:To identify CpG islands differentially methylated in pancreatic adenocarcinoma, we used methylated CpG island amplification (MCA) coupled with representational difference analysis. Of 42 CpG islands identified by MCA/representational difference analysis, 7 CpG islands [methylated in carcinoma of the pancreas (MICP)] were differentially methylated in a panel of eight pancreatic cancer cell lines compared with normal pancreas. In a larger panel of 75 pancreatic adenocarcinomas, these 7 MICPs (ppENK, Cyclin G, ZBP, MICP25, 27, 36, and 38) were methylated in 93, 3, 9, 15, 48, 19, and 41% of cancers, respectively, by methylation-specific PCR but not in any of 15 normal pancreata. In pancreatic cancer cell lines, methylation of ppENK, a gene with known growth suppressive properties, was associated with transcriptional silencing that was reversible with 5-aza-2'-deoxycytidine treatment. Relationships between the methylation patterns of pancreatic adenocarcinomas and their clinicopathological features were also determined. Larger pancreatic cancers and those from older patients (P = 0.017) harbored more methylated loci than smaller tumors and those from younger patients (P = 0.017). ppENK, MICP25, and 27 were variably methylated in normal gastric, duodenal, and colonic mucosae. These data indicate that aberrant methylation of ppENK and its transcriptional repression is a common event in pancreatic carcinogenesis.

journal_name

Cancer Res

journal_title

Cancer research

authors

Ueki T,Toyota M,Skinner H,Walter KM,Yeo CJ,Issa JP,Hruban RH,Goggins M

subject

Has Abstract

pub_date

2001-12-01 00:00:00

pages

8540-6

issue

23

eissn

0008-5472

issn

1538-7445

journal_volume

61

pub_type

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