Alterations of CDKN2 (MTS1/p16INK4A) gene in paraffin-embedded tumor tissues of human stomach, lung, cervix and liver cancers.

Jae-Ryong Kim,Seong-Yong Kim,Jung-Hye Kim,Mi-Jin Kim

doi:10.1038/emm.1998.16

Abstract

The CDKN2 (MTS1/p16INK4A) gene, encoding cyclin dependent kinase inhibitor, was found to be homozygously deleted at a high frequency in cell lines from many different types of cancer and some primary cancers. To determine the frequency of CDKN2 mutations in most common human cancers in Korea, PCR and PCR-SSCP analyses for the exon 2 of CDKN2 were performed on each set of 20 formalin-fixed and paraffin-embedded tumor tissues of stomach adenocarcinomas, lung cancers, cervix cancers and hepatocellular carcinomas. No mutations in exon 2 of CDKN2 were found in 20 stomach adenocarcinomas. In contrast to rare mutations in stomach adenocarcinomas, a high frequency of CDKN2 mutations was identified in other 3 cancers, 11 of 20 (55%) lung cancers (7 of 10 NSCLCs and 4 of 10 SCLCs), 14 of 20 (70%) cervix cancers and 11 of 20 (55%) hepatocellular carcinomas. These results suggest that mutations of the CDKN2 gene might be an important genetic change in NSCLCs, cervix cancers and hepatocellular carcinomas.

Highlights

Stomach, lung, cervix and hepatocellular cancers are the most common cancers in Korea
No deletions of exon 2 of the cyclin dependent kinase inhibitor 2 (CDKN2) gene and no mobility shifts of the amplified DNA fragments were identified in the 20 paraffin-embedded specimens of stomach adenocarcinomas (Figure 1)
To investigate the importance of CDKN2 mutations in tumors which occur at a high incidence in Korea, we examined the mutations on exon 2 of the CDKN2 gene in each set of 20 formalin-fixed and paraffin-embedded tumors of stomach adenocarcinomas, lung cancers, cervix cancers and hepatocellular carcinomas using polymerase chain reaction (PCR) and PCR-single strand conformation polymorphism (SSCP) analysis

Summary

Introduction

Lung, cervix and hepatocellular cancers are the most common cancers in Korea. Especially the reported mutation frequency of CDKN2 was controversial, varying from 0 to 52% in esophageal carcinomas (Mori et al, 1994; Okamoto et al, 1994; Suzuki et al, 1995), 7 to 83% in non-small cell lung cancers (de-Vos et al, 1995; Nakagawa et al, 1995; Xiao et al, 1995), and 4 to 36% in B-ALL (Schroder et al, 1995; Guidal-Giroux et al, 1996). In order to evaluate more accurately the alterations of CDKN2 in

Methods

Results

Conclusion