Analysis of TP53 Gene Mutations in the Korean Patients with Lung Cancer

Sang Bong Jung; Hee Kyung Chang; Seok Cheol Choi; Kyeong-Cheol Shin; Kwan-Ho Lee; Chang Ho Jeon

doi:10.3343/lmo.2011.1.4.6

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Jung, Chang, Choi, Shin, Lee, and Jeon: Analysis of TP53 Gene Mutations in the Korean Patients with Lung Cancer

Original Article

Diagnostic Genetics

Laboratory Medicine Online

Laboratory Medicine Online 2011; 1(4): 202-208.

Published online: 7 October 2011

DOI: https://doi.org/10.3343/lmo.2011.1.4.6

Analysis of TP53 Gene Mutations in the Korean Patients with Lung Cancer

Sang Bong Jung, MS¹, Hee Kyung Chang, M.D.¹, Seok Cheol Choi, Ph.D.², Kyeong-Cheol Shin, M.D.³, Kwan-Ho Lee, M.D.³, Chang Ho Jeon, M.D.⁴

¹Department of Pathology, Kosin University College of Medicine, Busan, Korea.

²Department of Clinical Laboratory Science, Catholic University, Busan, Korea.

³Department of Internal Medicine, College of Medicine, Yeungnam University, Daegu, Korea.

⁴Department of Laboratory Medicine, Daegu Catholic Medical Center, Daegu, Korea.

Corresponding author: Chang Ho Jeon, M.D. Department of Laboratory Medicine, Daegu Catholic Medical Center, 3056-6 Daemyung 4-dong, Nam-gu, Daegu 705-718, Korea. Tel: +82-53-650-4144, Fax: +82-53-653-8672, chjeon@cu.ac.kr

Received 5 March 2011 Revised 21 April 2011 Accepted 30 May 2011

(open-access):

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Lung cancer is one of the leading causes of cancer-related deaths throughout the world. The gene tumor protein 53 (TP53) is frequently mutated in cases of lung cancer. This study was performed to investigate the frequencies and types of mutations in the TP53 gene in Korean patients with lung cancer.

Methods

We obtained tissue samples from 80 lung cancer patients and synthesized TP53 cDNA by using RNA isolated from these tissues by performing reverse transcriptase polymerase chain reaction. Hybridization and denaturing high-performance liquid chromatography were performed to identify the TP53 gene mutations, and then, the mutations were validated by direct sequencing.

Results

Forty mutations out of the 80 patients (50.0%) were noted in the TP53 gene. The frequencies of TP53 gene mutation for different cancer types, namely, squamous cell carcinoma, adenocarcinoma, and small cell carcinoma were 61.1%, 27.3%, and 26.7%, respectively. The mutation frequencies in the different regions of the gene were 10.0% for exon 4, 35.0% for exon 5, 12.5% for exon 6, 22.5% for exon 7, 17.5% for exon 8, and 2.5% for exon 9. The frequently mutated positions were codon 179 in exon 5, codons 202 and 220 in exon 6, and codons 266 and 273 in exon 8.

Conclusions

Exon 5 was the most frequently mutated region in the TP53 gene. Compared to the patients with the other types of cancers, patients with squamous cell carcinoma showed a higher frequency of TP53 mutation. Codon 179 was the most frequently mutated codon in the TP53 gene.

Keywords: TP53 gene mutation, denaturing high performance liquid chromatography, exon, codon

Figures and Tables

Fig. 1

Denaturing high-performance liquid chromatography (DHPLC) analysis of exons 4-5 and 6-9.

Chromatograms obtained by performing DHPLC for exons 4-5 (A) and 6-9 (B) of wild type (a) and mutated (b) TP53 gene. The chromatograms for both the regions of the wild type gene were similar to those for the corresponding regions of the controls, while those for both the regions of the mutant genes were different from those for the corresponding regions of the controls.

Table 1

Characteristics of the lung cancer patients

Abbreviations: Sqcc, squamous cell carcinoma; Smcc, small cell carcinoma; Adeno, adenocarcinoma.

Table 2

Primer sequences used for detecting mutations in exons 4 to 9 of the TP53 gene

Abbreviation: bp, base pairs.

Table 3

TP53 mutation frequencies for the different types of lung carcinomas

^*One patient had a compound mutation at exon 6 and 8.

Table 4

Types of TP53 mutations in Korean patients with lung cancer

^*Novel mutation.

Abbreviations: Adeno, adenocarcinoma; Smcc, small cell carcinoma; Sqcc, squamous cell carcinoma; FS, frameshift; M, male; F, female; c, codon; p, protein.

Table 5

Comparison of our results with those of previous studies on lung cancer

Abbreviation: NT, not tested.

Notes

This article is available from http://www.labmedonline.org

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