Infrequent microsatellite instability in liver fluke infection-associated intrahepatic cholangiocarcinomas from Thailand
✍ Scribed by Upama Liengswangwong; Takayuki Nitta; Hironobu Kashiwagi; Hiroko Kikukawa; Toru Kawamoto; Takeshi Todoroki; Kazuhiko Uchida; Thiravud Khuhaprema; Anant Karalak; Petcharin Srivatanakul; Masanao Miwa
- Publisher
- John Wiley and Sons
- Year
- 2003
- Tongue
- French
- Weight
- 107 KB
- Volume
- 107
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Abstract
The liver fluke infection‐associated intrahepatic cholangiocarcinoma (ICC) is a major liver cancer in Northeast Thailand. The molecular basis of this ICC is poorly understood. To address possible roles of the DNA mismatch repair (MMR) system in ICC carcinogenesis, a fluorescence‐labeling PCR/laser scanning technique with high sensitivity was employed to analyze genomic instability in the nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) in 24 fresh and 13 formalin‐fixed, paraffin‐embedded tissues of ICC and their corresponding normal parts. Microsatellite instability (MSI) was assessed in nDNA, using 12 highly polymorphic loci including 5 Bethesda markers. These loci were mainly related to major MMR genes, hMSH2 and hMLH1. Also 3 (C)n and/or (C)n(A)n repeat instability at 1 noncoding region in the displacement‐loop (D‐loop) and 2 coding sequences in NADH dehydrogenase subunit 1 and subunit 5 gene in mtDNA were analyzed. MSI was only detected in 1 (2.7%), 6 (16.7%), 1 (2.9%), 1 (2.9%) or 2 (6.3%) out of 37, 36, 35, 35 or 32 cases at BAT‐25, D2S123, D3S1611, D11S904 or D17S250, respectively. LOH was found at D3S1298, D3S1561, D5S346 and TP53 in 4 (18.2%) out of 22, 2 (18.2%) out of 11, 6 (33.3%) out of 18 and 3 (12.5%) out of 24 informative cases, respectively. In mtDNA, none except a single case out of the 37 (2.7%) exhibited repeat sequence instability in the D‐loop. We conclude that the liver fluke infection‐associated ICC in Thailand is classified as low frequency MSI or microsatellite stable type and that DNA MMR system, through hMSH2 and hMLH1 gene mutations, does not play a major role in its carcinogenesis. © 2003 Wiley‐Liss, Inc.