Mutation analysis of TP53 in colorectal cancer, Peshawar, Khyber Pakhtunkhwa, Pakistan (original) (raw)
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Prognostic significance of TP53 gene mutation in 995 cases of colorectal carcinoma
European Journal of Cancer, 2000
Previous studies on the prognostic signi®cance of TP53 gene alterations in colorectal cancer (CRC) have led to con¯icting results. The present study investigated the prognostic signi®cance of TP53 gene mutation in a very large series of 995 Dukes' B and C CRC patients, the majority of whom did not receive chemotherapy. Mutations were found in 385 (39%) cases and were not associated with tumour stage, histological grade, patient age or sex. Signi®cantly more mutations were found in tumours from the left-sided colon compared with those from the right side (43% versus 34%, P=0.006). TP53 gene mutation had no prognostic value in the overall series or in dierent site or stage subgroups. None of the dierent types of TP53 gene mutation showed prognostic value. A trend for association with worse survival was observed in the patient subgroup that received adjuvant chemotherapy (Hazard Ratio (HR) 1.4, 95% con®dence interval (CI) 0.89±2.21, P=0.15). These results indicate that mutation of the TP53 gene is not a useful prognostic marker for CRC patients who do not receive adjuvant chemotherapy. Further study is required to determine whether dierent types of TP53 mutation might be of value in predicting the response of CRC patients to chemotherapy.
Molecular characterization of TP53 tumor suppressor gene in colorectal cancer
Revista Colombiana de Gastroenterologia
Introduction: Colorectal cancer (CRC) is one of the most common malignancies in the world, especially in developed countries. In Colombia, the incidence of CRC ranks fourth in men and women. CRC has great genetic heterogeneity. Purpose: The purpose of this study was to determine the presence of mutations in exons 5 to 8 of the TP53 gene in colorectal tumors by direct sequencing. Patients and Methods: Samples with histopathological diagnoses of sporadic CRC were divided into two groups. Group I included 30 tumor samples from fresh biopsies and Group II included 46 tumor tissue samples embedded in paraffi n blocks. Mutational analysis was performed for exons 5 through 8 of the TP53 gene using PCR and direct sequencing. Results: The frequency of TP53 mutations was only 4.4%, and mutations that were detected were nonsense mutations. In addition, two polymorphisms that segregate together were identifi ed. All mutations and polymorphisms were detected in samples from Group I. Most of the samples were in advanced stages of cancer. Conclusions: The low frequency of mutations in TP53 suggests the existence of alterations on other related genetic pathways in colorectal carcinogenesis. These could include MSI pathways, CIN and epigenetics. Such alterations could not be excluded in the samples tested. Molecular studies of tissue samples embedded in paraffi n are diffi cult to analyze genetically. Molecular characterization of CRC is important for determining the spectrum of mutations and molecular variants present in our population.
Annals of Oncology, 2006
Background: Loss of TP53 function through gene mutation is a critical event in the development and progression of many tumour types including colorectal cancer (CRC). In vitro studies have found considerable heterogeneity amongst different TP53 mutants in terms of their transactivating abilities. The aim of this work was to evaluate whether TP53 mutations classified as functionally inactive (£20% of wildtype transactivation ability) had different prognostic and predictive values in CRC compared with mutations that retained significant activity.
Analysis of P53 mutations and their expression in 56 colorectal cancer cell lines
Proceedings of the National Academy of Sciences, 2006
A comprehensive analysis of the TP53 gene and its protein status was carried out on a panel of 56 colorectal cancer cell lines. This analysis was based on a combination of denaturing HPLC mutation screening of all exons of the p53 gene, sequencing the cDNA, and assessing the function of the p53 protein by assaying the induced expression of phosphorylated p53 and p21 after exposing cells to γ-rays. In a few cases where there was no production of p53 message nor evidence of functional p53 protein, all of the p53 exons were sequenced directly. Thirteen of the 56 cell lines had functional p53, 21 lines had missense mutations (one of which made no detectable protein), 4 lines produced no p53 transcripts, and the remaining 18 lines carried truncating TP53 mutations. Thus, our results showed a relatively high frequency of TP53 mutations (76.8%) in our cell lines, with almost half of the mutations being truncating mutations. This is a rather higher frequency of such mutations than usually r...
TP53 somatic mutations and LOH profile in colorectal cancer in Romania
2017
Somatic mutations in TP53 tumor suppressor gene represent common events in colorectal cancer, followed frequently by loss of heterozygosity in the course of disease progression. In order to study the profile of these genetic alterations in Romanian oncologic patients TP53 gene sequencing and loss of heterozygosity analysis were performed in 62 tumor samples and 60 paired normal colon tissue samples collected during curative surgical resection. The rate of TP53 somatic mutations (46.8%) was concordant with published data while the type of mutations and their association with tumor sites exhibited a different pattern. The most prevalent mutation type was the nucleotide transition GC>AT (62.1% of total mutations) that occurred exclusively at the CpG dinucleotide sites. Allelic imbalance at TP53 locus was detected in 50% of colorectal tumors. The geographical variation of CRC might be explained by large differences in lifestyle habits and diet across various regions and ethnical grou...
Oncogene, 2004
We undertook a case-control study to examine the possible associations of the TP53 variants Arg4Pro at codon 72 and p53PIN3, a 16 bp insertion/duplication in intron 3, with the risk of colorectal cancer (CRC). The p53PIN3 A2 allele (16 bp duplication) was associated with an increased risk (OR 1.55, 95% CI 1.10À2.18, P ¼ 0.012), of the same order of magnitude as that observed in previous studies for other types of cancer. The Pro72 allele was weakly associated with CRC (OR ¼ 1.34, 95% CI 0.98À1.84, P ¼ 0.066). The possible functional role of p53PIN3 was investigated by examining the TP53 mRNA transcripts in 15 lymphoblastoid cell lines with different genotypes. The possibility that the insertion/deletion could lead to alternatively spliced mRNAs was excluded. However, we found reduced levels of TP53 mRNA associated with the A2 allele. In conclusion, the epidemiological study suggests a role for p53PIN3 in tumorigenesis, supported by the in vitro characterization of this variant.
p53 Exon 7 mutations as a predictor of poor prognosis in patients with colorectal cancer
Cancer Letters, 1998
We have studied 61 resected colorectal adenocarcinomas in order to investigate p53 mutations as a prognostic factor for this pathology. Mutations in exons 5-9 of the p53 gene were analyzed by the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) technique followed by sequencing. Our data indicate that p53 exon 7 mutations were prevalent in the latest stages of colorectal carcinogenesis and patients bearing this alteration had the worst prognosis. Therefore, according to our results, mutations affecting exon 7 of the p53 gene could be considered as a useful marker of biological aggressiveness for colorectal cancer.