Silencing of O-6-methylguanine DNA methyltransferase in the absence of promoter hypermethylation in hepatocellular carcinomas from Australia and South Africa

Herath, Nirmitha I., Walsh, Michael D., Kew, Michael, Smith, Jeffery L., Jass, Jeremy R., Young, Joanne, Leggett, Barbara A. and Macdonald, Graeme A. (2007) Silencing of O-6-methylguanine DNA methyltransferase in the absence of promoter hypermethylation in hepatocellular carcinomas from Australia and South Africa. Oncology Reports, 17 4: 817-822.

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Name Description MIMEType Size Downloads
Author Herath, Nirmitha I.
Walsh, Michael D.
Kew, Michael
Smith, Jeffery L.
Jass, Jeremy R.
Young, Joanne
Leggett, Barbara A.
Macdonald, Graeme A.
Title Silencing of O-6-methylguanine DNA methyltransferase in the absence of promoter hypermethylation in hepatocellular carcinomas from Australia and South Africa
Formatted title
Silencing of O6-methylguanine DNA methyltransferase in the absence of promoter hypermethylation in hepatocellular carcinomas from Australia and South Africa
Journal name Oncology Reports   Check publisher's open access policy
ISSN 1021-335X
Publication date 2007
Sub-type Article (original research)
Volume 17
Issue 4
Start page 817
End page 822
Total pages 6
Place of publication Athens, Greece
Publisher Professor D A Spandidos
Language eng
Subject 111299 Oncology and Carcinogenesis not elsewhere classified
Abstract The DNA repair protein O-6-methylguanine-DNA methyltransferase (MGMT) is involved in cellular defences against alkylating agents. Alterations in the MGMT gene may result in an increase in the mutation rate and risk of malignant transformation. We have previously shown that MGMT is implicated in colorectal carcinogenesis particularly in cancers which display microsatellite instability, a marker of impaired DNA repair. The aims of the current study were to assess the roles of MGMT and microsatellite instability in hepatocellular carcinomas (HCCs) from Australia and South Africa. DNA was extracted from malignant and non-malignant liver tissue from 37 Australian and 24 South African patients, and histologically normal liver from 20 transplant donors. MGMT promoter hypermethylation and MGMT protein expression were assessed using methylation specific PCR and immunohistochemistry. Microsatellite instability was examined using a panel of 23 microsatellite markers previously used to detect allelic imbalance and two specific markers for the detection of low levels of microsatellite instability. Methylation specific PCR did not detect any methylation of the MGMT promoter in Australian and South African HCCs. Similarly, no hypermethylation of MGMT was observed in the adjacent nonmalignant liver or histologically normal liver. MGMT staining was predominantly nuclear with some cytoplasmic staining. Overexpression of MGMT protein was detected in 14 (39%) HCCs, while a reduction in protein expression was evident in 14 (39%) HCCs. In the remaining 8 cases the expression of MGMT was comparable in HCCs and adjacent nonmalignant tissue. Interestingly, MGMT expression decreased relative to adjacent non-malignant liver tissue in patients who had aetiologies other than viral hepatitis for their underlying liver diseases (p < 0.02). No microsatellite instability was detected in this series of 61 HCCs. This suggests that epigenetic silencing of MGMT and microsatellite instability does not play an important role in this series of HCCs derived from different populations.
Keyword Oncology
hepatocellular carcinoma
O-6-methylguanine DNA methyltransferase
microsatellite instability
immunohistochemistry
Microsatellite Instability
O6-methylguanine-dna Methyltransferase
Colorectal-cancer
Cpg Islands
Gene
Methylation
Repair
Heterozygosity
Hepatitis
Mgmt
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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Created: Mon, 18 Feb 2008, 16:37:28 EST