CT findings of heterotopic pancreas in the stomach appear to be nonspecific for diagnosis, except for location.

The Popeye domain-containing (POPDC) genes BVES, POPDC2 and POPDC3 encode proteins that regulate cell-cell adhesion and cell migration during development. Herein, we report the frequent downregulation of BVES and POPDC3 by promoter hypermethylation in gastric cancer. POPDC expression in 11 gastric cancer cell lines and 96 paired gastric tumor and normal adjacent tissues was analyzed with quantitative reverse transcription-polymerase chain reaction. The methylation status of BVES and POPDC3 was analyzed with methylated DNA immunoprecipitation sequencing, bisulfite sequencing and pyrosequencing. Expression of BVES and POPDC3 was downregulated in 73% of the gastric cancer cell lines and in 69% (BVES) and 87% (POPDC3) of the gastric cancer tissues. The BVES and POPDC3 promoter regions were hypermethylated in the gastric cancer cell lines in which they were silenced. Combined treatment with a DNA methylation inhibitor and a histone deacetylase inhibitor strongly induced BVES and POPDC3 expression. BVES and POPDC3 were hypermethylated in 69% (BVES) and 64% (POPDC3) of the gastric cancer tissues. We knocked down POPDC3 expression with short hairpin RNAs and examined the consequences on cell migration and invasion. Knockdown of POPDC3 in SNU-216 cells caused increased cell migration and invasion. Thus, epigenetic inactivation of BVES and POPDC3 occurs frequently in gastric tumors and may promote gastric cancer cell migration and invasion.

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Leucine-rich repeat-containing 3B (LRRC3B) is an evolutionarily highly conserved leucine-rich repeat-containing protein, but its biological significance is unknown. Using restriction landmark genomic scanning and pyrosequencing, we found that the promoter region of LRRC3B was aberrantly methylated in gastric cancer. Gastric cancer cell lines displayed epigenetic silencing of LRRC3B, but treatment with the DNA methylation inhibitor 5-aza-2 ¶-deoxycytidine and/or the histone deacetylase inhibitor trichostatin A increased LRRC3B expression in gastric cancer cell lines. Real-time reverse transcription-PCR analysis of 96 paired primary gastric tumors and normal adjacent tissues showed that LRRC3B expression was reduced in 88.5% of gastric tumors compared with normal adjacent tissues. Pyrosequencing analysis of the promoter region revealed that LRRC3B was significantly hypermethylated in gastric tumors. Stable transfection of LRRC3B in SNU-601 cells, a gastric cancer cell line, inhibited anchorage-dependent and anchorage-independent colony formation, and LRRC3B expression suppressed tumorigenesis in nude mice. Microarray analysis of LRRC3B-expressing xenograft tumors showed induction of immune responserelated genes and IFN signaling genes. H&E-stained sections of LRRC3B-expressing xenograft tumors showed lymphocyte infiltration in the region. We suggest that LRRC3B is a putative tumor suppressor gene that is silenced in gastric cancers by epigenetic mechanisms and that LRRC3B silencing in cancer may play an important role in tumor escape from immune surveillance. [Cancer Res 2008;68(17):7147-55]

The promoter region of Discoidin, CUB and LCCL domain containing 2 (DCBLD2) was found to be aberrantly methylated in gastric cancer cell lines and in primary gastric cancers, as determined by restriction landmark genomic scanning. DCBLD2 expression was inversely correlated with DCBLD2 methylation in gastric cancer cell lines. Treatment with 5-aza-2 ¶-deoxycytidine and trichostatin A partially reversed DCBLD2 methylation and restored gene expression in DCBLD2-silenced cell lines. In an independent series of 82 paired gastric cancers and adjacent normal tissues, DCBLD2 expression was down-regulated in 79% of gastric cancers as compared with normal tissues as measured by real-time reverse transcription-PCR. Pyrosequencing analysis of the DCBLD2 promoter region revealed abnormal hypermethylation in gastric cancers, and this hypermethylation was significantly correlated with down-regulation of DCBLD2 expression. Furthermore, ectopic expression of DCBLD2 in gastric cancer cell lines inhibited colony formation in both anchorage-dependent and anchorage-independent cultures and also inhibited invasion through the collagen matrix. These data suggest that downregulation of DCBLD2, often associated with promoter hypermethylation, is a frequent event that may be related to the development of gastric cancer. (Mol Cancer Res 2008;6(2):222 -30)