EBV Conference 2008 Guangzhou - Baylor College of Medicine

175 (RegID: 1132)
Qian Tao
Institution: Chinese University of Hong Kong
e-mail: qtao@clo.cuhk.edu.hk
INTEGRATIVE CANCER EPIGENTICS IDENTIFIES A NOVEL RAB GTPASE AS A
FUNCTIONAL TUMOR SUPPRESSOR FREQUENTLY SILENCED IN NASOPHARYNGEAL
AND MULTIPLE OTHER CARCINOMAS
Jisheng Li, Jianming Ying, Hongyu Li, Ka Man Ng, Qian Tao
Posterabstract:
Epigenetic silencing of tumor suppressor genes (TSGs) through methylation of promoter CpG islands
(CGI) contributes to the pathogenesis of multiple cancers including nasopharyngeal carcinoma (NPC).
TSGs often locate at frequently deleted chromosome regions. We utilized an integrative genomic
epigenetic approach by combining high-resolution array comparative genomic hybridization (aCGH) with
epigenetic profiling to screen for epigenetically inactivated TSGs. A 1.5-Mb deletion at 11q22 was refined
by aCGH in multiple tumor cell lines, indicating the presence of critical TSGs. Semi-quantitative RT-PCR
analysis revealed that TUSC12 gene was downregulated in multiple carcinoma cell lines, in contrast to its
broad expression in normal adult and fetal tissues. TUSC12 belongs to the RAB GTPase family, which is
involved in the regulation of vesicular membrane traffic and associated with multiple human diseases
including cancer. Frequent promoter methylation of TUSC12 was detected in multiple carcinoma cell lines
including esophageal, nasopharyngeal, colon, breast, hepatocellular and gastric carcinomas, as well as
primary tumors, but not in immortalized normal epithelial cell lines. Furthermore, transcriptional silencing
of TUSC12 could be reversed by pharmacologic demethylation with 5-aza-2’-deoxycytidine, indicating a
direct epigenetic inactivation. Ectopic expression of TUSC12 in tumor cells lacking its expression
dramatically inhibited their clonogenicity, confirming the tumor suppressor function of this gene. Thus, a
RAB GTPase TUSC12 was identified as a novel TSG with frequently epigenetic silencing in multiple
carcinomas.
EBV Conference 2008 Guangzhou
- 243 -