Genotypic and phenotypic characterization of a putative tumor susceptibility gene, GNMT, in liver cancer

Tzu Ling Tseng, Yi Ping Shih, Yu Chuen Huang, Chung Kwe Wang, Pao Huei Chen, Jan Gowth Chang, Kun Tu Yeh, Yi Ming Arthur Chen, Kenneth H. Buetow

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Glycine N-methyltransferase (GNMT), a multifunctional protein involved in the maintenance of the genetic stability, is often down-regulated in hepatocellular carcinoma (HCC). Using genotypic characterization of GNMT in hepatoma cell lines and in a Taiwanese population with a high incidence of liver cancer we have investigated the role of this gene in the progression of liver cancer. Six novel polymorphisms, including two short tandem repeats, one 4-nucleotide insertion/deletion polymorphism, and three single nucleotide polymorphisms, in GNMT were identified in this study. The rates of loss of heterozygosity at the GNMT locus in pairs of normal and tumor tissue from the HCC patients were approximately 36-47%. In addition, the observed heterozygosity of GNMT decreases in tumor adjacent liver DNA from HCC patients compared with that observed in blood DNA from normal individuals and HCC patients. This may result from the early event of loss of heterozygosity within the GNMT gene in the liver tissues of HCC patients. However, in this study, we did not observe the association of polymorphic GNMT alleles as inherited risk factors for HCC. We also elucidated the functional impact of genetic markers in the GNMT promoter by performing luciferase reporter gene and gel mobility shift assays. The results indicate that two polymorphisms, short tandem repeat 1 and insertion/deletion polymorphism, in the promoter region could cause allelic specific effects on the transcriptional activity of GNMT. The risk genotypes of GNMT, which presumably have a lower expression level, as estimated from in vitro functional studies, are over-represented in tumor-adjacent tissues from HCC patients. In summary, our results suggest that GNMT alteration may be an early event in HCC development and that GNMT could be a new tumor susceptibility gene for HCC.

Original languageEnglish
Pages (from-to)647-654
Number of pages8
JournalCancer Research
Volume63
Issue number3
Publication statusPublished - Feb 1 2003
Externally publishedYes

Fingerprint

Glycine N-Methyltransferase
Liver Neoplasms
Hepatocellular Carcinoma
Genes
Neoplasms
Loss of Heterozygosity
Microsatellite Repeats
Liver
DNA
Electrophoretic Mobility Shift Assay

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Tseng, T. L., Shih, Y. P., Huang, Y. C., Wang, C. K., Chen, P. H., Chang, J. G., ... Buetow, K. H. (2003). Genotypic and phenotypic characterization of a putative tumor susceptibility gene, GNMT, in liver cancer. Cancer Research, 63(3), 647-654.

Genotypic and phenotypic characterization of a putative tumor susceptibility gene, GNMT, in liver cancer. / Tseng, Tzu Ling; Shih, Yi Ping; Huang, Yu Chuen; Wang, Chung Kwe; Chen, Pao Huei; Chang, Jan Gowth; Yeh, Kun Tu; Chen, Yi Ming Arthur; Buetow, Kenneth H.

In: Cancer Research, Vol. 63, No. 3, 01.02.2003, p. 647-654.

Research output: Contribution to journalArticle

Tseng, TL, Shih, YP, Huang, YC, Wang, CK, Chen, PH, Chang, JG, Yeh, KT, Chen, YMA & Buetow, KH 2003, 'Genotypic and phenotypic characterization of a putative tumor susceptibility gene, GNMT, in liver cancer', Cancer Research, vol. 63, no. 3, pp. 647-654.
Tseng TL, Shih YP, Huang YC, Wang CK, Chen PH, Chang JG et al. Genotypic and phenotypic characterization of a putative tumor susceptibility gene, GNMT, in liver cancer. Cancer Research. 2003 Feb 1;63(3):647-654.
Tseng, Tzu Ling ; Shih, Yi Ping ; Huang, Yu Chuen ; Wang, Chung Kwe ; Chen, Pao Huei ; Chang, Jan Gowth ; Yeh, Kun Tu ; Chen, Yi Ming Arthur ; Buetow, Kenneth H. / Genotypic and phenotypic characterization of a putative tumor susceptibility gene, GNMT, in liver cancer. In: Cancer Research. 2003 ; Vol. 63, No. 3. pp. 647-654.
@article{8c016ef0f6144f5c99f1c6fe5f3c22a9,
title = "Genotypic and phenotypic characterization of a putative tumor susceptibility gene, GNMT, in liver cancer",
abstract = "Glycine N-methyltransferase (GNMT), a multifunctional protein involved in the maintenance of the genetic stability, is often down-regulated in hepatocellular carcinoma (HCC). Using genotypic characterization of GNMT in hepatoma cell lines and in a Taiwanese population with a high incidence of liver cancer we have investigated the role of this gene in the progression of liver cancer. Six novel polymorphisms, including two short tandem repeats, one 4-nucleotide insertion/deletion polymorphism, and three single nucleotide polymorphisms, in GNMT were identified in this study. The rates of loss of heterozygosity at the GNMT locus in pairs of normal and tumor tissue from the HCC patients were approximately 36-47{\%}. In addition, the observed heterozygosity of GNMT decreases in tumor adjacent liver DNA from HCC patients compared with that observed in blood DNA from normal individuals and HCC patients. This may result from the early event of loss of heterozygosity within the GNMT gene in the liver tissues of HCC patients. However, in this study, we did not observe the association of polymorphic GNMT alleles as inherited risk factors for HCC. We also elucidated the functional impact of genetic markers in the GNMT promoter by performing luciferase reporter gene and gel mobility shift assays. The results indicate that two polymorphisms, short tandem repeat 1 and insertion/deletion polymorphism, in the promoter region could cause allelic specific effects on the transcriptional activity of GNMT. The risk genotypes of GNMT, which presumably have a lower expression level, as estimated from in vitro functional studies, are over-represented in tumor-adjacent tissues from HCC patients. In summary, our results suggest that GNMT alteration may be an early event in HCC development and that GNMT could be a new tumor susceptibility gene for HCC.",
author = "Tseng, {Tzu Ling} and Shih, {Yi Ping} and Huang, {Yu Chuen} and Wang, {Chung Kwe} and Chen, {Pao Huei} and Chang, {Jan Gowth} and Yeh, {Kun Tu} and Chen, {Yi Ming Arthur} and Buetow, {Kenneth H.}",
year = "2003",
month = "2",
day = "1",
language = "English",
volume = "63",
pages = "647--654",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "3",

}

TY - JOUR

T1 - Genotypic and phenotypic characterization of a putative tumor susceptibility gene, GNMT, in liver cancer

AU - Tseng, Tzu Ling

AU - Shih, Yi Ping

AU - Huang, Yu Chuen

AU - Wang, Chung Kwe

AU - Chen, Pao Huei

AU - Chang, Jan Gowth

AU - Yeh, Kun Tu

AU - Chen, Yi Ming Arthur

AU - Buetow, Kenneth H.

PY - 2003/2/1

Y1 - 2003/2/1

N2 - Glycine N-methyltransferase (GNMT), a multifunctional protein involved in the maintenance of the genetic stability, is often down-regulated in hepatocellular carcinoma (HCC). Using genotypic characterization of GNMT in hepatoma cell lines and in a Taiwanese population with a high incidence of liver cancer we have investigated the role of this gene in the progression of liver cancer. Six novel polymorphisms, including two short tandem repeats, one 4-nucleotide insertion/deletion polymorphism, and three single nucleotide polymorphisms, in GNMT were identified in this study. The rates of loss of heterozygosity at the GNMT locus in pairs of normal and tumor tissue from the HCC patients were approximately 36-47%. In addition, the observed heterozygosity of GNMT decreases in tumor adjacent liver DNA from HCC patients compared with that observed in blood DNA from normal individuals and HCC patients. This may result from the early event of loss of heterozygosity within the GNMT gene in the liver tissues of HCC patients. However, in this study, we did not observe the association of polymorphic GNMT alleles as inherited risk factors for HCC. We also elucidated the functional impact of genetic markers in the GNMT promoter by performing luciferase reporter gene and gel mobility shift assays. The results indicate that two polymorphisms, short tandem repeat 1 and insertion/deletion polymorphism, in the promoter region could cause allelic specific effects on the transcriptional activity of GNMT. The risk genotypes of GNMT, which presumably have a lower expression level, as estimated from in vitro functional studies, are over-represented in tumor-adjacent tissues from HCC patients. In summary, our results suggest that GNMT alteration may be an early event in HCC development and that GNMT could be a new tumor susceptibility gene for HCC.

AB - Glycine N-methyltransferase (GNMT), a multifunctional protein involved in the maintenance of the genetic stability, is often down-regulated in hepatocellular carcinoma (HCC). Using genotypic characterization of GNMT in hepatoma cell lines and in a Taiwanese population with a high incidence of liver cancer we have investigated the role of this gene in the progression of liver cancer. Six novel polymorphisms, including two short tandem repeats, one 4-nucleotide insertion/deletion polymorphism, and three single nucleotide polymorphisms, in GNMT were identified in this study. The rates of loss of heterozygosity at the GNMT locus in pairs of normal and tumor tissue from the HCC patients were approximately 36-47%. In addition, the observed heterozygosity of GNMT decreases in tumor adjacent liver DNA from HCC patients compared with that observed in blood DNA from normal individuals and HCC patients. This may result from the early event of loss of heterozygosity within the GNMT gene in the liver tissues of HCC patients. However, in this study, we did not observe the association of polymorphic GNMT alleles as inherited risk factors for HCC. We also elucidated the functional impact of genetic markers in the GNMT promoter by performing luciferase reporter gene and gel mobility shift assays. The results indicate that two polymorphisms, short tandem repeat 1 and insertion/deletion polymorphism, in the promoter region could cause allelic specific effects on the transcriptional activity of GNMT. The risk genotypes of GNMT, which presumably have a lower expression level, as estimated from in vitro functional studies, are over-represented in tumor-adjacent tissues from HCC patients. In summary, our results suggest that GNMT alteration may be an early event in HCC development and that GNMT could be a new tumor susceptibility gene for HCC.

UR - http://www.scopus.com/inward/record.url?scp=0037308777&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037308777&partnerID=8YFLogxK

M3 - Article

VL - 63

SP - 647

EP - 654

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 3

ER -