Jingcui Yu " /> Peng Liu " /> " /> " /> " /> Rongwei Guan " /> " /> " /> " /> Yuzhen Zhao" /> " /> Yan Jin " /> Jing Bai " /> Ki-Young Lee " /> *" /> Jingcui Yu, Peng Liu, Xiaobo Cui, Yu Sui, Guohua Ji, Rongwei Guan, Donglin Sun, Wei Ji, Fangli Liu, An Liu, Yuzhen Zhao, Yang Yu, Yan Jin, Jing Bai, Jingshu Geng, Yingwei Xue, Jiping Qi, Ki-Young Lee, Songbin Fu*" /> Jingcui Yu, Peng Liu, Xiaobo Cui, Yu Sui, Guohua Ji, Rongwei Guan, Donglin Sun, Wei Ji, Fangli Liu, An Liu, Yuzhen Zhao, Yang Yu, Yan Jin, Jing Bai, Jingshu Geng, Yingwei Xue, Jiping Qi, Ki-Young Lee, Songbin Fu*. Mol. Cells 2011;32:47-55. https://doi.org/10.1007/s10059-011-2316-4">
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Mol. Cells 2011; 32(1): 47-55

Published online July 31, 2011

https://doi.org/10.1007/s10059-011-2316-4

© The Korean Society for Molecular and Cellular Biology

Identification of Novel Subregions of LOH in Gastric Cancer and Analysis of the HIC1 and TOB1 Tumor Suppressor Genes in These Subregions

Jingcui Yu1,2,7, Peng Liu1,7, Xiaobo Cui1,7, Yu Sui1, Guohua Ji1, Rongwei Guan1, Donglin Sun1, Wei Ji1, Fangli Liu1, An Liu1, Yuzhen Zhao1, Yang Yu1, Yan Jin1,3, Jing Bai1, Jingshu Geng4, Yingwei Xue4, Jiping Qi5, Ki-Young Lee6, Songbin Fu1,*

1Laboratory of Medical Genetics, Harbin Medical University, Harbin 150081, China, 2The Second Affiliated Hospital, Harbin Medical University, Harbin 150081, China, 3Key Laboratory of Medical Genetics, Harbin Medical University, Heilongjiang Higher Education Institutions, China, 4The Third Affiliated Hospital, Harbin Medical University, Harbin 150081, China, 5The First Affiliated Hospital, Harbin Medical University, Harbin 150081, China, 6Department of Cell Biology and Anatomy, University of Calgary, Calgary, Canada, 7These authors contributed equally to this work.

Correspondence to : *Correspondence: fusb@ems.hrbmu.edu.cn

Received: December 21, 2011; Revised: March 25, 2011; Accepted: April 4, 2011

Abstract

Previously, we identified 3 overlapping regions showing loss of heterozygosity (LOH, R1-R3 from 11 to 30 cM) on chromosome 17 in 45 primary gastric cancers (GCs). The data indicated the presence of tumor suppressor genes (TSGs) on chromosome 17 involved in GC. Among the putative TSGs in these regions, HIC1 (in SR1) and TOB1 (in SR3) remain to be examined in GC. By immunohistochemistry (IHC), methylation-specific PCR (MSP) and western blot, we evaluated the expression and regulation status for HIC1 and TOB1 protein in GC. We narrowed down the deletion intervals on chromosome 17 and defined five smaller LOH subregions, SR1-SR5 (0.54 to 3.42 cM), in GC. We found that HIC1 had downregulated expression in 86% (91/106) and was methylated in 87% (26/30) of primary GCs. Of the primary GCs showing downregulation of HIC1 protein, 75% (18/24) had methylated HIC1 gene. TOB1 was either absent or expressed at reduced levels in 75% (73/97) of the GC samples. In addition, a general reduction was found in total and the ratio of unphosphorylated to phosphorylated TOB1 protein levels in the differentiated GC cell lines. Further analysis revealed significant simultaneous downregulation of both HIC1 and TOB1 protein in GC tissue microarray samples (67%, 52/78) and in primary GCs (65%, 11/17). These results indicate that silencing of HIC1 and TOB1 expression is a common occurrence in GC and may contribute to the development and progression of the disease.

Keywords gastric cancer, HIC1, loss of heterozygosity, methylation, TOB1

Article

Research Article

Mol. Cells 2011; 32(1): 47-55

Published online July 31, 2011 https://doi.org/10.1007/s10059-011-2316-4

Copyright © The Korean Society for Molecular and Cellular Biology.

Identification of Novel Subregions of LOH in Gastric Cancer and Analysis of the HIC1 and TOB1 Tumor Suppressor Genes in These Subregions

Jingcui Yu1,2,7, Peng Liu1,7, Xiaobo Cui1,7, Yu Sui1, Guohua Ji1, Rongwei Guan1, Donglin Sun1, Wei Ji1, Fangli Liu1, An Liu1, Yuzhen Zhao1, Yang Yu1, Yan Jin1,3, Jing Bai1, Jingshu Geng4, Yingwei Xue4, Jiping Qi5, Ki-Young Lee6, Songbin Fu1,*

1Laboratory of Medical Genetics, Harbin Medical University, Harbin 150081, China, 2The Second Affiliated Hospital, Harbin Medical University, Harbin 150081, China, 3Key Laboratory of Medical Genetics, Harbin Medical University, Heilongjiang Higher Education Institutions, China, 4The Third Affiliated Hospital, Harbin Medical University, Harbin 150081, China, 5The First Affiliated Hospital, Harbin Medical University, Harbin 150081, China, 6Department of Cell Biology and Anatomy, University of Calgary, Calgary, Canada, 7These authors contributed equally to this work.

Correspondence to:*Correspondence: fusb@ems.hrbmu.edu.cn

Received: December 21, 2011; Revised: March 25, 2011; Accepted: April 4, 2011

Abstract

Previously, we identified 3 overlapping regions showing loss of heterozygosity (LOH, R1-R3 from 11 to 30 cM) on chromosome 17 in 45 primary gastric cancers (GCs). The data indicated the presence of tumor suppressor genes (TSGs) on chromosome 17 involved in GC. Among the putative TSGs in these regions, HIC1 (in SR1) and TOB1 (in SR3) remain to be examined in GC. By immunohistochemistry (IHC), methylation-specific PCR (MSP) and western blot, we evaluated the expression and regulation status for HIC1 and TOB1 protein in GC. We narrowed down the deletion intervals on chromosome 17 and defined five smaller LOH subregions, SR1-SR5 (0.54 to 3.42 cM), in GC. We found that HIC1 had downregulated expression in 86% (91/106) and was methylated in 87% (26/30) of primary GCs. Of the primary GCs showing downregulation of HIC1 protein, 75% (18/24) had methylated HIC1 gene. TOB1 was either absent or expressed at reduced levels in 75% (73/97) of the GC samples. In addition, a general reduction was found in total and the ratio of unphosphorylated to phosphorylated TOB1 protein levels in the differentiated GC cell lines. Further analysis revealed significant simultaneous downregulation of both HIC1 and TOB1 protein in GC tissue microarray samples (67%, 52/78) and in primary GCs (65%, 11/17). These results indicate that silencing of HIC1 and TOB1 expression is a common occurrence in GC and may contribute to the development and progression of the disease.

Keywords: gastric cancer, HIC1, loss of heterozygosity, methylation, TOB1

Mol. Cells
Jan 31, 2023 Vol.46 No.1, pp. 1~67
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RNAs form diverse shapes and play multiple functions as central molecules of gene expression. In this special issue on RNA, seven minireviews illustrate how basic concepts and recent RNA biology findings are transformed into new and exciting RNA therapeutics.

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