Microsatellite Instability of Nuclear and Mitochondrial DNAs in Gastric Carcinogenesis

Jae-Ho Lee,Dae-Kwang Kim

doi:10.7314/apjcp.2014.15.19.8027

Jae-Ho Lee, Dae-Kwang Kim

Open Access

https://doi.org/10.7314/apjcp.2014.15.19.8027

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Abstract

Genetic instability contributes to the development and progression of gastric cancer, one of the leading causes of cancer death worldwide. Microsatellite instability (MSI) has been hypothesized to be involved in carcinogenesis, althgough its mechanisms and exact roles in gastric cancer remain largely unknown. Our aim was to identify associated clinicopathological characteristics and prognostic value of MSI in gastric cancer and precancerous lesions including gastritis, metaplasia, dysplasia, and adenoma. Because mitochondrial DNA has a different genetic system from nuclear DNA, the results of both nuclear MSI and mitochondrial MSI in gastric cancer were reviewed. This review provides evidence that genetic instability of nuclear and mitochondrial DNAs contributes to early stages of gastric carcinogenesis and suggests possible roles in predicting prognosis.

Highlights

Gastric cancer (GC) is highly prevalent in Asia and the third most common cause of cancer death after lung cancer and liver cancer in Korea (Jung et al, 2012)
This review provides evidence that genetic instability of nuclear and mitochondrial DNAs contributes to early stages of gastric carcinogenesis and suggests possible roles in predicting prognosis
We and other groups investigated mitochondrial genetic instability in GC and precancerous legions (Maximo et al, 2001; Ling et al, 2004; Zhao et al, 2005; Lee et al, 2007; Jeong et al, 2010). These results show the change of mitochondrial DNA may be early event in gastric carcinogenesis and suggest its potential for progression of GC

Summary

Introduction

Gastric cancer (GC) is highly prevalent in Asia and the third most common cause of cancer death after lung cancer and liver cancer in Korea (Jung et al, 2012). In gastric precancerous legions adjacent to GC, the frequency of MSI was different according to the markers examined for MSI detection (Semba et al, 1996; Hamamoto et al, 1997; Kobayashi et al, 2000; Leung et al, 2000; Jin et al, 2001; Kim et al, 2002; Lee et al, 2002; Lee et al, 2004; Zaky et al, 2008). The studies using other markers showed rare frequency of MSI in precancerous legions adjacent to GC (Semba et al, 1996; Hamamoto et al, 1997; Kobayashi et al, 2000; Jin et al, 2001) These results suggested that the pathway of gastric carcinogenesis may be different between precancerous legions adjacent to GC and that without GC. Kashiwagi et al (2000) showed the gastritis with MSI developed into gastric adenoma or adenocarcinoma and suggested MSI as a possible marker for predicting

MSI Markers

Bethesda panel

Findings

Conclusion