Frequency of TP53 Mutations in Relation to Arg72Pro Genotypes in Non–Small Cell Lung Cancer

Abstract

Mutations in the TP53 gene are important events during human lung carcinogenesis. The TP53 gene harbors several polymorphisms, and functional studies have shown that the Arg72Pro polymorphism alters both wild-type and mutant p53 protein activity. Thus, we hypothesized that certain Arg72Pro genotypes may influence the frequency and pattern of somatic mutations in TP53. We therefore examined the status of the Arg72Pro polymorphism and TP53 mutations in 260 non -small-cell lung cancer cases. Here we report a significant trend toward lower frequency of TP53 mutations with increasing number of Pro72 alleles (P = 0.02). Overall, Pro72 allele carriers had significantly lower frequency of TP53 mutations compared with Arg72 homozygotes (P = 0.02). In addition, carriage of the Pro72 variant was related to a lower frequency of mutations affecting the hotspot codon 273. Mutations at codon 273 accounted for 10.6% of the mutations in Arg72 homozygotes and 1.7% of the mutations in Pro72 allele carriers. Our results suggest that the genotype of the Arg72Pro polymorphism may modulate the frequency of TP53 mutations in nonsmall-cell lung cancer. (Cancer Epidemiol Biomarkers Prev 2007;16(10):2077 -81)

Association between the TP53 Arg72Pro polymorphism and clinical outcomes in acute myeloid leukemia

“…7 Finally, Pro72 allele carriers show significantly lower frequency of TP53 mutations in specific types of human non-hematologic tumors. 13 Here, we demonstrated that the TP53 Pro/Pro genotype was associated with higher risk of leukemia and favorable outcome in AML patients treated with conventional therapy, particularly those assigned to the intermediate cytogenetic risk group. Therefore, it seems that the TP53 Arg72Pro polymorphism may have different tissue-and context-specific functions, and the prognostic importance of each allele may depend on the type of cancer and on the particular treatment.…”

Functional effect of polymorphisms in 15q25 locus on CHRNA5 mRNA, bulky DNA adducts and TP53 mutations

“…Interassay variation was generally <20%. Analysis of TP53 mutations in lung tumor tissues was performed as previously described 20…”

New targeted approaches against the ubiquitin–proteasome system in gastrointestinal malignancies

“…Alternatively, p53 degradation is prevented by inhibition of the Mdm2 regulator p14 ARF, or by deubquitination by HAUSP [33][34][35][36][37]. The Hdm2 gene is amplified in approximately 10% of solid tumors [36] and mutations in the HAUSP and Hdm2 genes are frequently associated with non-small-cell lung cancer and colorectal cancer [38][39][40].…”