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Microsatellite instability and MLH1 promoter hypermethylation in colorectal cancer.结直肠癌中的微卫星不稳定性和MLH1启动子高甲基化
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Gallbladder cancer worldwide: geographical distribution and risk factors.全球胆囊癌：地理分布与风险因素
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High-level microsatellite instability is not involved in gallbladder carcinogenesis.高度微卫星不稳定性与胆囊癌发生无关。
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Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability.遗传性非息肉病性结直肠癌（林奇综合征）和微卫星不稳定性的修订版贝塞斯达指南
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日本和匈牙利高发病区胆囊癌中p53、K-ras的基因变化及微卫星不稳定性

Genetic changes of p53, K-ras, and microsatellite instability in gallbladder carcinoma in high-incidence areas of Japan and Hungary.

作者信息

Nagahashi Masayuki, Ajioka Yoichi, Lang Istvan, Szentirmay Zoltan, Kasler Miklos, Nakadaira Hiroto, Yokoyama Naoyuki, Watanabe Gen, Nishikura Ken, Wakai Toshifumi, Shirai Yoshio, Hatakeyama Katsuyoshi, Yamamoto Masaharu

机构信息

Division of Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata 951-8510, Japan.

出版信息

World J Gastroenterol. 2008 Jan 7;14(1):70-5. doi: 10.3748/wjg.14.70.

DOI:10.3748/wjg.14.70
PMID:18176964
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2673394/
Abstract

AIM

To disclose geographic differences in genetic changes involved in gallbladder carcinogenesis between two distinct high-incidence areas of Japan and Hungary.

METHODS

We examined 42 cases of gallbladder carcinoma: 22 Japanese and 20 Hungarian cases. p53 mutations at exons 5 to 8 and K-ras mutations at codon 12 were tested by direct sequencing. Microsatellite instability was determined from fluorescent dye-labeled PCR amplifications of five-microsatellite markers (BAT-25, BAT-26, D2S123, D5S346, and D17S250).

RESULTS

Mutations of p53 were detected in 11 of 22 Japanese cases and 6 of 18 Hungarian cases (11/22 vs 6/18, P = 0.348). Transition at CpG sites was found in none of 11 Japanese cases and 2 of 6 Hungarian cases; the difference was marginally significant (0/11 vs 2/6, P = 0.110). K-ras mutations were detected in only one of the Hungarian cases. Eight of 19 (42.1%) Japanese cases were MSI-high (presence of novel peaks in more than one of the five loci analyzed), whereas only 1 of 15 (6.7%) Hungarian cases was MSI-high (P = 0.047).

CONCLUSION

It appears that the p53 mutations and MSI differ in patients with gallbladder carcinoma between two distinct high-incidence areas. Geographic variation might exist in the process of gallbladder carcinogenesis.

摘要

目的

揭示日本和匈牙利两个不同高发地区胆囊癌发生过程中基因变化的地理差异。

方法

我们检查了42例胆囊癌病例：22例日本病例和20例匈牙利病例。通过直接测序检测第5至8外显子的p53突变和密码子12处的K-ras突变。微卫星不稳定性通过对五个微卫星标记（BAT-25、BAT-26、D2S123、D5S346和D17S250）进行荧光染料标记的PCR扩增来确定。

结果

在22例日本病例中有11例检测到p53突变，18例匈牙利病例中有6例检测到p53突变（11/22对6/18，P = 0.348）。在11例日本病例中均未发现CpG位点的转换，而6例匈牙利病例中有2例发现；差异具有边缘显著性（0/11对2/6，P = 0.110）。仅在1例匈牙利病例中检测到K-ras突变。19例（42.1%）日本病例中有8例微卫星高度不稳定（在分析的五个位点中的一个以上出现新峰），而15例（6.7%）匈牙利病例中只有1例微卫星高度不稳定（P = 0.047）。

结论

两个不同高发地区胆囊癌患者的p53突变和微卫星高度不稳定似乎存在差异。胆囊癌发生过程中可能存在地理差异。