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CpG island methylator phenotype association with elevated serum alpha-fetoprotein level in hepatocellular carcinoma.
Clin Cancer Res. 2007 Feb 01; 13(3):944-52.CC

Abstract

PURPOSE

CpG island methylator phenotype (CIMP) involves hypermethylation targeted toward the promoters of multiple genes. To gain insight into the role of epigenetic aberration of tumor-related genes in hepatocarcinogenesis, we determined a hypermethylation profile in hepatocellular carcinoma (HCC).

EXPERIMENTAL DESIGN

We examined the promoter methylation status of nine genes in 50 HCCs, 50 paired nontumor tissues, and 6 normal liver tissues by methylation-specific PCR. CIMP+ was defined as having five genes that are concordantly methylated.

RESULTS

The frequency of promoter methylation of nine genes in 50 HCCs varied from 10% in P53 to 94% in c-Myc. The methylation status of P14, P15, P16, ER, RASSF1A, WT1, and c-Myc was significantly correlated with HCC and nontumor tissues (P<0.05). Hypermethylation of one or more genes was found in 96% of HCC. CIMP was more frequent in HCC than in nontumor tissues (70% and 12%, P<0.001). There is a significant association between CIMP and methylation of P14, P15, P16, ER, RSAAF1A, and WT1 (P<0.05) and serum alpha-fetoprotein (AFP) level (P=0.017). CIMP+ was more frequent in HCC with AFP>or=30 microg/L than those with AFP<30 microg/L (P=0.005). In addition, the promoter hypermethylation of P15 and P16 was associated with elevated serum AFP levels in 35 HCC samples with CIMP+ (P<0.05).

CONCLUSIONS

Positive correlation of CIMP and AFP levels in HCC suggests that CIMP can serve as a molecular marker of late-stage HCC development.

Authors+Show Affiliations

Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17289889

Citation

Zhang, Changsong, et al. "CpG Island Methylator Phenotype Association With Elevated Serum Alpha-fetoprotein Level in Hepatocellular Carcinoma." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 13, no. 3, 2007, pp. 944-52.
Zhang C, Li Z, Cheng Y, et al. CpG island methylator phenotype association with elevated serum alpha-fetoprotein level in hepatocellular carcinoma. Clin Cancer Res. 2007;13(3):944-52.
Zhang, C., Li, Z., Cheng, Y., Jia, F., Li, R., Wu, M., Li, K., & Wei, L. (2007). CpG island methylator phenotype association with elevated serum alpha-fetoprotein level in hepatocellular carcinoma. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 13(3), 944-52.
Zhang C, et al. CpG Island Methylator Phenotype Association With Elevated Serum Alpha-fetoprotein Level in Hepatocellular Carcinoma. Clin Cancer Res. 2007 Feb 1;13(3):944-52. PubMed PMID: 17289889.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CpG island methylator phenotype association with elevated serum alpha-fetoprotein level in hepatocellular carcinoma. AU - Zhang,Changsong, AU - Li,Zhengyou, AU - Cheng,Yue, AU - Jia,Fengqi, AU - Li,Rong, AU - Wu,Mengchao, AU - Li,Ke, AU - Wei,Lixin, PY - 2007/2/10/pubmed PY - 2007/5/5/medline PY - 2007/2/10/entrez SP - 944 EP - 52 JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin Cancer Res VL - 13 IS - 3 N2 - PURPOSE: CpG island methylator phenotype (CIMP) involves hypermethylation targeted toward the promoters of multiple genes. To gain insight into the role of epigenetic aberration of tumor-related genes in hepatocarcinogenesis, we determined a hypermethylation profile in hepatocellular carcinoma (HCC). EXPERIMENTAL DESIGN: We examined the promoter methylation status of nine genes in 50 HCCs, 50 paired nontumor tissues, and 6 normal liver tissues by methylation-specific PCR. CIMP+ was defined as having five genes that are concordantly methylated. RESULTS: The frequency of promoter methylation of nine genes in 50 HCCs varied from 10% in P53 to 94% in c-Myc. The methylation status of P14, P15, P16, ER, RASSF1A, WT1, and c-Myc was significantly correlated with HCC and nontumor tissues (P<0.05). Hypermethylation of one or more genes was found in 96% of HCC. CIMP was more frequent in HCC than in nontumor tissues (70% and 12%, P<0.001). There is a significant association between CIMP and methylation of P14, P15, P16, ER, RSAAF1A, and WT1 (P<0.05) and serum alpha-fetoprotein (AFP) level (P=0.017). CIMP+ was more frequent in HCC with AFP>or=30 microg/L than those with AFP<30 microg/L (P=0.005). In addition, the promoter hypermethylation of P15 and P16 was associated with elevated serum AFP levels in 35 HCC samples with CIMP+ (P<0.05). CONCLUSIONS: Positive correlation of CIMP and AFP levels in HCC suggests that CIMP can serve as a molecular marker of late-stage HCC development. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/17289889/CpG_island_methylator_phenotype_association_with_elevated_serum_alpha_fetoprotein_level_in_hepatocellular_carcinoma_ L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&amp;pmid=17289889 DB - PRIME DP - Unbound Medicine ER -