Visit our Expo - Redox and Inflammation signaling 2012

Session XIV : Transcriptional and translational control Poster XIV, 30
Expression and Regulation of various tumor suppressor genes in Gastrointestinal
Stromal Tumor
Keun Hur, Hyuk-Joon Lee, Han-Kwang Yang.
Cancer Research Institute Seoul National University College of Medicine 28 Yongon-
Dong, Chongno-Gu, Seoul, Korea 110-744. E-mail: blue2001@snu.ac.kr (alternate email:
longcoat@hanmail.net )
Gastrointestinal stromal tumors (GISTs) are Kit/CD117 expressing mesenchymal tumors.
Aberrant hypermethylation of promoter CpG islands is an important mechanism for the
inactivation of tumor suppressor genes. CpG island hypermethylation occurs in relation to
tumorigenesis in many human tumors. Moreover, we have previously reported that
transcriptional repression of Cox-2 is caused by hyper-methylation of the Cox-2 promoter
region CpG island in human gastric carcinoma (BBRC., 310(3), 844-851, 2003). The
pathogenesis of GISTs involves a gain-of-function mutation in the KIT proto-oncogene,
leading to ligand-independent constitutive activation of the KIT receptor. KIT-wild-type
GISTs have shown mutually exclusive platelet-derived growth factor receptor (PDGFR)
mutation and activation. However, the data on the methylation status of various tumor
suppressor genes and mutation status of KIT and PDGFR in GISTs has been very limited. We
attempted to determine the methylation status of 12 genes (APC, COX-2, GSTP1, MGMT,
p14, p16, RUNX-3, THBS-1, TIMP-3, DAP-kinase, E-cadherin, RASSF1A), in 30 human
gastrointestinal stromal tumor tissues. In addition, we confirmed the mutation status of KIT
and PDGFR genes in 30 human gastrointestinal stromal tumor tissues. Thirty c-kit-positive
Gastrointestinal stromal tumors were selected for this study. Genomic DNAs and RNAs from
human Gastrointestinal stromal tumors were analyzed for the relationship between expression
and methylation status by cDNA microarray and methylation specific PCR (MSP). CpG
island hyper-methylation was found in 40% for APC, 46% for COX-2, 16% for GSTP1, 26%
for MGMT, 60% for p14, 30% for p16, 16% for RUNX-3, 23% for THBS-1, 10% for TIMP-
3, 20% for DAP-kinase, 36% for E-cadherin, 10% for RASSF1A. Our results suggest that the
DNA methylation-mediated transcriptional silencing of various tumor suppressor genes is a
predominant mechanism for the down-regulation of various tumor suppressor genes
expression in human gastrointestinal stromal tumors.
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