Mutation analysis of K-ras and β-catenin genes related toO6-methylguanin-DNA methyltransferase and mismatch repair protein status in human gallbladder carcinoma

Kohya,Naohiko; Kitajima,Yoshihiko; Kitahara,Kenji; Miyazaki,Kohji

doi:10.3892/ijmm.11.1.65

January 2003 Volume 11 Issue 1

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January 2003 Volume 11 Issue 1

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Article

Mutation analysis of K-ras and β-catenin genes related toO6-methylguanin-DNA methyltransferase and mismatch repair protein status in human gallbladder carcinoma

Authors:
- Naohiko Kohya
- Yoshihiko Kitajima
- Kenji Kitahara
- Kohji Miyazaki
View Affiliations / Copyright

Affiliations: Department of Surgery, Saga Medical School, Saga 849-8501, Japan
Pages: 65-69
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Published online on: January 1, 2003

https://doi.org/10.3892/ijmm.11.1.65
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Abstract

O6-Methylguanin-DNA methyltransferase (MGMT) is a DNA repair enzyme that transfers methyl groups from O6-methylguanine to itself. Alkylation of DNA at the O6 position of guanine is the first step by alkylating agents in inducing DNA mutations in an organism. When MGMT and the mismatch repair (MMR) system are impaired, O6-methylguanine mispairs with thymine during DNA replication, resulting in a G:C↷A:T transitional mutation in DNA. We obtained cancer lesions by manual micro-dissection (MMD) from 26 paraffin-embedded formalin-fixed gallbladder carcinoma and Laser Capture Micro-dissection (LCM) method from 10 fresh frozen specimens. Mutation analysis was performed on the micro-dissected samples for K-ras and β-catenin genes. At codon 12 of the K-ras gene, the MMD and LCM methods detected mutations in 3 (11.5%) and 1 (10%) case, respectively. In exon 3 of β-catenin gene, only 1 (3.8%) case revealed a mutation in MMD cancer foci. Two cases without MGMT or MMR expression revealed a G↷A transition mutation in the K-ras gene. The findings suggested that negative MGMT and MMR status contributed to a G:C↷A:T transitional mutation in the K-ras gene. However, K-ras and β-catenin mutations were actually rare in GB carcinoma. Other gene mutations frequently occurring in gallbladder carcinoma might be affected by this negative MGMT and MMR status.

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Mutation analysis of K-ras and β-catenin genes related toO6-methylguanin-DNA methyltransferase and mismatch repair protein status in human gallbladder carcinoma

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