Epigenetic down-regulation of CDKN1C/p57KIP2 in pancreatic ductal neoplasms identified by gene expression profiling.

摘要: Purpose: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is an increasingly identified precursor to infiltrating ductal adenocarcinoma. Although our knowledge clinical and pathologic features IPMNs increasing, molecular mechanisms underlying these neoplasms remain poorly understood. Experimental Designs: To provide further insight into pathobiology IPMNs, global expression profiling was done determine genes that are inactivated/down-regulated in using oligonucleotide microarrays (Affymetrix). Results: In total, 300 unique transcripts (217 known genes) were as highly underexpressed 12 ( P CDKN1C/p57KIP2 . CDKN1C also decreased many pancreatic cancer cell lines restored following treatment with a DNA methylation inhibitor (5-aza-2′-deoxycitidine) or, more potently, histone deacetylase (trichostatin A). Partial promoter CpG island found most, but not all, reduced expression, detectable IPMNs. Furthermore, subset cancers showed complete hypomethylation LIT1 , imprinting control region important for regulation expression. Complete result deletion methylated allele at 11p15.5 rather than loss imprinting. Conclusions: These findings suggest commonly down-regulated through combination hypermethylation, deacetylation, maternal expressing