Aberrant DNA methylation precedes loss of heterozygosity on chromosome 16 in chronic hepatitis and liver cirrhosis.

作者: Yae Kanai , Saori Ushijima , Hitoshi Tsuda , Michiie Sakamoto , Setsuo Hirohashi

DOI: 10.1016/S0304-3835(99)00316-X

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摘要: The aim of this study was to examine the significance aberrant DNA methylation, participation which in genetic instability is controversial, hepatocarcinogenesis. methylation status region around promoter E-cadherin tumor suppressor gene, located on 16q22.1, and allelic at D16S421 locus, adjacent were examined using microdissected liver specimens from 38 hepatocellular carcinoma (HCC) patients. Almost all non-cancerous tissues showed histological findings compatible with chronic hepatitis cirrhosis, are considered be precancerous conditions. hypermethylation detected 61% tissues. incidence patients HCCs also showing (72%) significantly higher than that without their (53%, P<0.05). Loss heterozygosity (LOH) locus 35% LOH 78%, whereas not HCCs. Fifty-two percent both or neither LOH; alone noncancerous tissue 41%. (7%) lower compared those former two cases (P<0.0001). These data suggest participates stage hepatocarcinogenesis by preceding, causing, LOH.

参考文章(35)
P. Rabbitts, R. Rudd, G. Sinha, P. Hasleton, P. Ganly, N. M. Bleehen, V. Sundaresan, p53 and chromosome 3 abnormalities, characteristic of malignant lung tumours, are detectable in preinvasive lesions of the bronchus Oncogene. ,vol. 7, pp. 1989- 1997 ,(1992)
T L Kautiainen, P A Jones, DNA methyltransferase levels in tumorigenic and nontumorigenic cells in culture. Journal of Biological Chemistry. ,vol. 261, pp. 1594- 1598 ,(1986) , 10.1016/S0021-9258(17)35981-1
Peter A Jones, Peter W Laird, Cancer-epigenetics comes of age Nature Genetics. ,vol. 21, pp. 163- 167 ,(1999) , 10.1038/5947
Joshua M. Stolker, Stephen B. Baylin, Nita Ahuja, Jean Pierre J. Issa, Avinash L. Mohan, James G. Herman, Stanley R. Hamilton, Qing Li, Association between CpG Island Methylation and Microsatellite Instability in Colorectal Cancer Cancer Research. ,vol. 57, pp. 3370- 3374 ,(1997)
Richard Z. Chen, Ulf Pettersson, Caroline Beard, Laurie Jackson-Grusby, Rudolf Jaenisch, DNA hypomethylation leads to elevated mutation rates Nature. ,vol. 395, pp. 89- 93 ,(1998) , 10.1038/25779
Rikuo Machinami, Okio Hino, Keiko Ohtake, Tomoyuki Kitagawa, Hideaki Yasui, Clonal Growth of Hepatitis B Virus-integrated Hepatocytes in Cirrhotic Liver Nodules Cancer Research. ,vol. 52, pp. 6810- 6814 ,(1992)
Setsuo Hirohashi, Koichi Kobayashi, Yae Kanai, Keisuke Eguchi, DNA Hypermethylation at the D17S5 Locus in Non-Small Cell Lung Cancers: Its Association with Smoking History Cancer Research. ,vol. 57, pp. 4913- 4915 ,(1997)
J Toguchida, T Sakai, N Ohtani, D W Yandell, T P Dryja, J M Rapaport, Allele-specific hypermethylation of the retinoblastoma tumor-suppressor gene. American Journal of Human Genetics. ,vol. 48, pp. 880- 888 ,(1991)
Yae Kanai, Ai-Min Hui, Lin Sun, Saori Ushijima, Michiie Sakamoto, Hitoshi Tsuda, Setsuo Hirohashi, DNA hypermethylation at the D17S5 locus and reduced HIC-1 mRNA expression are associated with hepatocarcinogenesis. Hepatology. ,vol. 29, pp. 703- 709 ,(1999) , 10.1002/HEP.510290338