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

  • Published online on: January 1, 2003     https://doi.org/10.3892/ijmm.11.1.65
  • Pages: 65-69
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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.

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January 2003
Volume 11 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Kohya N, Kitajima Y, Kitahara K and Miyazaki K: Mutation analysis of K-ras and β-catenin genes related toO6-methylguanin-DNA methyltransferase and mismatch repair protein status in human gallbladder carcinoma. Int J Mol Med 11: 65-69, 2003.
APA
Kohya, N., Kitajima, Y., Kitahara, K., & Miyazaki, K. (2003). Mutation analysis of K-ras and β-catenin genes related toO6-methylguanin-DNA methyltransferase and mismatch repair protein status in human gallbladder carcinoma. International Journal of Molecular Medicine, 11, 65-69. https://doi.org/10.3892/ijmm.11.1.65
MLA
Kohya, N., Kitajima, Y., Kitahara, K., Miyazaki, K."Mutation analysis of K-ras and β-catenin genes related toO6-methylguanin-DNA methyltransferase and mismatch repair protein status in human gallbladder carcinoma". International Journal of Molecular Medicine 11.1 (2003): 65-69.
Chicago
Kohya, N., Kitajima, Y., Kitahara, K., Miyazaki, K."Mutation analysis of K-ras and β-catenin genes related toO6-methylguanin-DNA methyltransferase and mismatch repair protein status in human gallbladder carcinoma". International Journal of Molecular Medicine 11, no. 1 (2003): 65-69. https://doi.org/10.3892/ijmm.11.1.65