+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

High frequency of promoter hypermethylation of RASSF1A and p16 and its relationship to aflatoxin B1-DNA adduct levels in human hepatocellular carcinoma

, : High frequency of promoter hypermethylation of RASSF1A and p16 and its relationship to aflatoxin B1-DNA adduct levels in human hepatocellular carcinoma. Molecular Carcinogenesis 35(2): 85-92

Epigenetic changes in gene expression due to extensive CpG island methylation is now accepted as the main cause of inactivation of the p16 gene. More recently, it has been suggested that the human ras association domain family (RASSF) 1 gene, cloned from the lung tumor-suppressor locus 3p21.3, also may be inactivated by methylation. It consists of two major alternative transcripts, RASSF1A and RASSF1C. Epigenetic inactivation of isoform A was observed in several carcinomas and tumor cell lines. In this study, promoter hypermethylation of RASSF1A and p16 was investigated in 83 hepatocellular carcinoma (HCC) tissue samples from Taiwan and in two HCC cell lines (Hep3B and HepG2). High frequencies (85% and 47%, respectively) of methylation of the CpG island promoters of RASSF1A and p16 were found in the HCC tissues. The methylation of RASSF1A also was detected in Hep3B cells but not in HepG2 cells; p16 was not methylated in either cell line. Methylation status was determined in 12 normal control liver tissues and 10 adjacent nontumor tissues. No methylation was found in normal liver control tissues for both RASSF1A and p16; methylation was detected in one of 10 and seven of 10 adjacent nontumor tissue sampless for p16 and RASSF1A, respectively, in subjects with positive tumors. These data indicate that aberrant methylation of the CpG island promoters of both genes is a frequent occurrence in hepatocarcinogenesis. The high frequency of RASSF1A methylation in adjacent tissues suggests that this may be an early event. The relationship between methylation status and clinical parameters and tumor markers, including DNA damage resulting from aflatoxin B(1) (AFB(1)), an environmental carcinogen, and p53 status, also was analyzed. A statistically significant association was found between RASSF1A methylation status and the level of AFB(1)-DNA adducts in tumor tissues. No association was found between methylation status and p53 status. These results suggest the hypothesis that exposure to environmental carcinogens may be involved in altered methylation of genes involved in cancer development.


PMID: 12325038

DOI: 10.1002/mc.10076

Other references

Lebedeva, G.V.; Gel'fand, Y.V.; Riznichenko, G.Y.; Turovetskii, V.B., 1993: Fluctuations in intracellular pH and the character of its distribution in a population of immunocompetent cells. Biophysics (English Translation of Biofizika) 38(3): 439-443

Tomaz, R.A.; Harman, J.L.; Karimlou, D.; Weavers, L.; Fritsch, L.; Bou-Kheir, T.; Bell, E.; Del Valle Torres, I.; Niakan, K.K.; Fisher, C.; Joshi, O.; Stunnenberg, H.G.; Curry, E.; Ait-Si-Ali, S.; Jørgensen, H.F.; Azuara, Véronique., 2017: Jmjd2c facilitates the assembly of essential enhancer-protein complexes at the onset of embryonic stem cell differentiation. Jmjd2 H3K9 demethylases cooperate in promoting mouse embryonic stem cell (ESC) identity. However, little is known about their importance at the exit of ESC pluripotency. Here, we reveal that Jmjd2c facilitates this process by stabilising the assem...

WangJie; TianGuoZhong; XuQiCong; LiuYongGuang; GaoRui; LiXiangDong; ZhuXiaoPing, 2010: Molecular detection of phytoplasma strains from several plants around diseased paulownia infected with paulownia witches-broom phytoplasma. Objective: The objective of this study is to investigate and identify the alternative host plants of paulownia witches'-broom phytoplasma (PaWB) in natural condition. Method: Using universal primers for phytoplasmal 16S rRNA gene, nested PCR...

Schulenburg-Brand, D.; Kumar, N.; Zouwail, S., 2014: The impact of local guidelines on the tumour marker requesting patterns of a General Surgery Department. The inappropriate use of tumour markers (TMs) is a common problem. The aim of this audit was to evaluate the impact of local guidelines on the TM requesting patterns of a General Surgery Department. CA 125, CA 19-9, CA15-3, CEA, AFP and HCG reques...

Anonymous, 1956: CASE RECORDS of the Massachusetts General Hospital; case 42432. New England Journal of Medicine 255(17): 823-825

Loog Aadu; Petersell Valter; Aruvali Jaan; Kalkun Mare, 1998: Methods for the determination of the texture and mineral composition of the Dictyonema Shale. The Tremadoc (Lower Ordovician) Dictyonema Shale is an organic-rich lithified clay. To determine its texture and mineral composition, the samples of strongly compacted but not metamorphosed shale were disintegrated, and the organic matter, amorpho...

Elliott, J.; Hems, D.A.; Beloff-Chain, A., 1971: Carbohydrate metabolism of the isolated perfused liver of normal and genetically obese--hyperglycaemic (ob-ob) mice. 1. A technique for perfusion of the mouse liver has been developed, and aspects of carbohydrate metabolism have been investigated in the perfused liver of normal and genetically obese mice, homozygous for the recessive gene ob. 2. Rates of glucone...

Nelson, P.; Glenny, A-M.; Kirk, S.; Caress, A-L., 2012: Parents' experiences of caring for a child with a cleft lip and/or palate: a review of the literature. This review brings together for the first time the existing quantitative and qualitative research evidence about the experiences of parents caring for a child with a cleft. It summarizes salient themes on the emotional, social and service-related...

Nyhlen, A.; Johansson, J., 1964: Controlled atmosphere storage of apples, 1957-1960. Ingrid Marie apples from orchards on 3 different soil types were harvested on 4 or 5 dates, were graded and then stored in CA storage (8% CO2 and 13% O2), in a refrigerated store or in plastic liners. In all stores the temperature was 3.5 degrees...

Friedman, M., 1966: The changing image of human nature. The philosophical aspect. American Journal of Psychoanalysis 26(2): 138-147