J Korean Med Sci.  2010 May;25(5):698-705. 10.3346/jkms.2010.25.5.698.

TP53 Mutations in Korean Patients with Non-small Cell Lung Cancer

• Lee EB
• Jin G
• Lee SY
• Park JY
• Kim MJ
• Choi JE
• Jeon HS
• Cha SI
• Cho S
• Kim CH
• Park TI
• Jung TH
• Son JW
• Park JY

• KMID: 1713952
• DOI: http://doi.org/10.3346/jkms.2010.25.5.698

Abstract

Although TP53 mutations have been widely studied in lung cancer, the majority of studies have focused on exons 5-8 of the gene. In addition, TP53 mutations in Korean patients with lung cancers have not been investigated. We searched for mutations in the entire coding exons, including splice sites of the gene, in Korean patients with non-small cell lung cancer (NSCLC). Mutations of the gene were determined by direct sequencing in 176 NSCLCs. Sixty-nine mutations (62 different mutations) were identified in 65 tumors. Of the 62 mutations, 12 were novel mutations. TP53 mutations were more frequent in males, ever-smokers and squamous cell carcinomas than in females, never-smokers and adenocarcinomas, respectively (all comparisons, P<0.001). Missense mutations were most common (52.2%), but frameshift, nonsense, and splice-site mutations were frequently observed at frequencies of 18.8%, 15.9% and 10.1%, respectively. Of the 69 mutations, 9 (13.0%) were found in the oligomerization domain. In addition, the proportion of mutations in the oligomerization domain was significantly higher in adenocarcinomas than in squamous cell carcinomas (23.5% vs. 2.9%, P=0.01). Our study provides clinical and molecular characteristics of TP53 mutations in Korean patients with NSCLCs.

Keyword

Lung Neoplasms; Mutation; Genes, p53

MeSH Terms

Carcinoma, Non-Small-Cell Lung/*epidemiology/*genetics
Female
Genetic Predisposition to Disease/*epidemiology/*genetics
Humans
Incidence
Korea/epidemiology
Lung Neoplasms/*epidemiology/*genetics
Male
Middle Aged
Polymorphism, Single Nucleotide/genetics
Risk Assessment/methods
Risk Factors
Tumor Suppressor Protein p53/*genetics
Tumor Suppressor Protein p53

Figure

• 

  Fig. 1 Overview of 69 TP53 mutations. E2-E11 do not reflect the real size of each exon, but are approximately proportional to the frequency of mutations. The position of each bar indicates the approximate location of each mutation. The height of each bar correlates with the frequency of the mutation at each location. *1, P128_A129 del; *2, P177_C182 del; *3, I195_N200 del. E, exon; TAD, transactivation domain; DBD, DNA-binding domain; OD, oligomerization domain.

• 

  Fig. 2 TP53 mutation pattern. SCC, squamous cell carcinoma; AC, adenocarcinoma. Number in parentheses, percentage.

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