Abstract:
:Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Little is known about its molecular pathogenesis and the relevance of DNA methylation for disease initiation and progression. Nevertheless, promoter methylation of some genes has been implicated as potential marker for HCC. Thirty-four HCC, 34 matching non-malignant, cirrhotic livers and 16 normal livers were analyzed for the methylation status of the genes p16(INK4a), GSTP1, MGMT, DAP-K and APC by quantitative methylation-specific PCR. DNA promoter methylation frequencies in HCC and matching non-malignant cirrhotic liver, respectively, were as follows: p16(INK4a) (76% vs. 24%), GSTP1 (53% vs. 32%), MGMT (6 vs. 12%), DAP-K (68 vs. 100%) and APC (100 vs. 100%). GSTP1 and/or p16(INK4a) promoter methylation was observed in 88% of the HCC samples. In normal liver tissue, the p16(INK4a), GSTP1 and MGMT promoter were not methylated. DAP-K was methylated in 31% and APC even in 100% of normal liver samples. Quantitative levels of methylated promoter DNA of all genes were significantly different in the various tissue types except for MGMT. Our results suggest that promoter methylation of tumor-associated genes is a common event in hepatocarcinogenesis. Significantly, higher levels and frequencies of promoter methylation in HCC were found for p16(INK4a) and GSTP1 compared to non-malignant cirrhotic liver. This indicates that these epigenetic events may serve as a good marker for HCC. These data also demonstrate the importance of the quantification of methylated promoter DNA within a given sample and the use of normal tissue as controls. Quantitative analyses of methylated GSTP1 and p16(INK4a) promoter may serve as a powerful molecular marker in detecting HCC in biopsies.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Harder J,Opitz OG,Brabender J,Olschewski M,Blum HE,Nomoto S,Usadel Hdoi
10.1002/ijc.23433subject
Has Abstractpub_date
2008-06-15 00:00:00pages
2800-4issue
12eissn
0020-7136issn
1097-0215journal_volume
122pub_type
杂志文章abstract::Urinary bladder cancer is a heterogeneous disease with tumors ranging from papillary noninvasive (stage Ta) to solid muscle infiltrating tumors (stage T2+). The risk of progression and death for the most frequent diagnosed type, Ta, is low, but the high incidence of recurrences has a significant effect on the patients...
journal_title:International journal of cancer
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abstract::The growth properties of a human melanoma cell line (MeWo) and of a variant (MeWo-LC1) endowed with higher metastatic potential in nude mice were compared using hormonally-defined serum-free media. The two cell lines failed to arrest in G0 following serum deprivation, and responded to INS and MSA but not to EGF, PDGF ...
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