• Asian Pacific Journal of Cancer Prevention
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• 제16권16호
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• pp.6845-6849
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• 2015

Background: Roles of tobacco and alcohol use in etiology of cancer are well established. Alterationin in P53 have essential roles neoplastic change by preventing genome mutation; the aim of this study was to assess the association between P53 mutation and tobacco and alcohol consumption, as well as to assess the epidemiology of tobacco and alcohol use as risk factors for cancer in the adult population of northern Saudi civilians. Materials and Methods: A cross-sectional survey from October 2014 to January 2015, covering 3,398 adults, was performed. P53 mutation molecular detection was performed for 100 tobacco and alcohol users, usingDNA extracted from buccal cells. Results: Of the 3,398 participants 3,253/3398(95.7%) responded, with a male female ratio of 1.10: 1.00. Out of these, 24.8% had smoked tobacco in their lifetime and 2.7% were consumers of alcoholic beverages. None was identified with any P53 mutation. Conclusions: The prevalence of tobacco smoking among the northern Saudi civilians was relatively high. Females' attitudes in tobacco and alcohol related issues were found to be affected by social stigma. Tobacco and alcohol use has no link to P53 gene mutations.

• Asian Pacific Journal of Cancer Prevention
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• 제15권4호
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• pp.1603-1609
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• 2014

Background: The response to treatment and overall survival (OS) of patients with acute myeloid leukemia (AML) is variable, with a median ranging from 6 months to 11.5 years. TP53 is associated with old age, chemotherapy resistance, and worse OS. Using genetic sequencing, we set out to look at our own experience with AML, and hypothesized that both TP53 mutations and SNPs at codon 72 would mimic the literature by occurring in a minority of patients, and conferring a worse OS. Materials and Methods: We performed a pilot study of randomly selected, newly diagnosed AML patients at Mount Sinai Medical Center, diagnosed from 2005-2008 (n=10). TP53 PCR sequencing was performed using DNA from bone marrow smears. Analysis was accomplished using Mutation Surveyor software with confirmation of the variants using the COSMIC and dbSNP databases. Results: Fewer than half of the patients harbored TP53 mutations (40%). There was no significant difference in OS based on gender, AML history, risk-stratified karyotype, or TP53 mutation. There were possible trends toward improved survival among patients less than 60 (11 vs 4 months, p=0.09), Hispanics (8 vs 1 months, p=0.11), and those not harboring SNP P72R (8 vs 2 months, p=0.10). There was a significant improvement in survival among patients with better performance status (28 vs 4 months, p=0.01) and those who did not have a complex karyotype (8 vs 1 months, p=0.03). The most commonly observed TP53 mutation was a missense N310K (40%) and the most commonly observed SNP was P72R (100.0%). Conclusions: Our study confirms previous reports that poor PS and the presence of a complex karyotype are associated with a decreased OS. In our cohort, TP53 mutations were relatively common, occurring more frequently in male patients with an adverse karyotype. Although there was no significant difference in survival between TP53 mutated and un-mutated patients, there was a possible trend toward worse OS among patients with SNP P72R. Larger studies are needed to validate these findings.

• Asian Pacific Journal of Cancer Prevention
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• 제13권11호
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• pp.5535-5538
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• 2012

Background: There have been case reports of oral squamous cell carcinoma arising from gingival overgrowth induced by phenytoin - an antiepileptic drug. However, a detailed analysis for the presence of mutations in p53 and ras genes, which are the two most frequently mutated genes in cancers, in phenytoin induced gingival overgrowth tissues has hitherto not been performed. Methods: Cellular DNA isolated from twenty gingival overgrowth tissues collected from patients undergoing phenytoin therapy were amplified using primers for p53 (exons 5-8) and H-ras (exons 1-2) genes. The PCR amplicons were then gel purified and subjected to direct sequencing analysis to screen for mutations. Results: Direct sequencing of twenty samples of phenytoin induced gingival growth did not identify mutations in any of the exons of p53 and H-ras genes that were analyzed. Conclusion: Our result indicates that mutational alteration of p53 and H-ras genes is infrequent in phenytoin induced gingival growth, which thus suggests a non malignant nature of this pathology. The findings in the present study are clinically significant as a large number of epileptic patients are treated with phenytoin.

• Tuberculosis and Respiratory Diseases
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• 제40권6호
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• pp.653-658
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• 1993

연구배경 : 최근 분자유전학의 진보로 인하여 암은 다단계의 복잡한 과정을 거쳐 발생됨이 밝혀졌으며, 이러한 단계는 크게 암유전자의 활성화와 종양억제 유전자의 비활성화로 구분하게 되었다. 본 연구는 p53 종양억제 유전자에 대하여 연구하였는데, 이는 p53 유전자의 변이는 현재까지 밝혀진 종양억제 유전자중 가장 광범위한 종류의 암에서 변이가 확인되고 있기 때문이다. 폐암은 우리나라에서 비교적 흔한 암이나 분자유전학적 발암기전은 아직 불분명하다. 본 연구에서는 폐암 발생에 있어 p53 유전자의 역할을 연구하고자 사람 폐암세포주를 대상으로 p53 유전자중 변이가 높은 비율로 발생되는 영역으로 알려진 exon 4-8에 대한 유전자 변이를 연구하였다. 방법 : 사람 폐선암 세포주인 PC-9와 PC-14 그리고 사람 소세포폐암 세포주인 H69를 대상으로 proteinase K에 의한 소화와 phenol-chloroform-ethanol 방법으로 genomic DNA를 추출하였다. 추출한 DNA를 p53 유전자중 exon 4-8 영역에 대한 primer를 사용하여 polymerase chain reaction(PCR)을 하여 각 exon에 대한 DNA를 증폭시킨 뒤 single strand conformation polymorphism(SSCP) 방법으로 전기영동과 자기방사기록을 하여 전기영동상 이동변화를 관찰하여 변이를 연구하였다. 결과 : 사람 폐선암세포주인 PC-9와 PC-14 에서는 exon 7에, 사람 소세포폐암 세포주인 H69에서는 exon 5에서 전기영동상 이동변화가 관찰되어 이 영역에 p53 유전자 변이가 있음이 인정되었다. 결론 : 대상으로 하엿던 3종류의 사람 폐암세포주 모두에서 p53 유전자의 변이가 확인된 것은 p53 종양억제 유전자의 변이가 비소세포 및 소세포 폐암 발생에 중요한 역할을 하고 있음을 시사하는 소견으로 사료된다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권6호
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• pp.3503-3507
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• 2013

Background: Although the majority of investigations concerned with TP53 and its protein have focused on coding regions, recently a set of studies highlighted significant roles of regulatory elements located in p53 mRNA, especially 5'UTR. The wrap53${\alpha}$ transcript is one of those that acts as a natural antisense agent, forming RNA-RNA hybrids with p53 mRNA and protecting it from degradation. Materials and Methods: In this study, we focused on the mutation status of exon $1{\alpha}$ of the WRAP53 gene (according to exon 1 of p53) in 160 breast tumor tissue samples and conducted a bioinformatics search for probable miRNA binding site in the p53/wrap53 overlapping region. Mutations were detected, using single stranded conformation polymorphism (SSCP) and sequencing. We applied the miRBase database for prediction of miRNAs which target overlapping region of p53/wrap53 transcripts. Results: Our results showed all samples to have wild type alleles in exon 1 of TP53 gene. We could detect a novel and unreported intronic mutation (IVS1+56, G>C) outside overlapping regions of p53/wrap53 genes in breast cancer tissues and also predict the presence of a binding site for miR-4732-5p in the 5'UTR of Wrap53 mRNA. Conclusions: From our findings we propose designing further studies focused on overexpression of miRNA-4732-5p and introducing different mutations in the overlapping region of wrap53 and p53 genes in order to study their effects on p53 and its ${\Delta}N$ isoform (${\Delta}$40p53) expression. The results may provide new pieces in the p53 targeting puzzle for cancer therapy.

• Asian Pacific Journal of Cancer Prevention
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• 제15권13호
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• pp.5449-5454
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• 2014

Although genetic characteristics are considered to be a factor influencing the geographic variation in the prevalence of gallbladder cancer (GBC), they have not been well studied in Bolivia, which has a high prevalence rate of GBC. The purpose of this study was to examine the frequency of TP53 and K-ras mutations in Bolivian patients with GBC and to compare them with our previous data obtained in other high-GBC-prevalence countries, namely Japan, Chile, and Hungary. DNA was extracted from cancer sites in paraffin-embedded tissue from 36 patients using a microdissection technique. TP53 mutations at exons 5 to 8 and K-ras mutations at codons 12, 13 and 61 were examined using direct sequencing techniques. The data obtained were compared with those in the other high-GBC-prevalence countries. Of the 36 patients, 18 (50.0%) had a TP53 mutation (one mutation in each of 17 patients and three mutations in one patient), and only one (2.8%) had a K-ras mutation. Of the 20 TP53 mutations, 12 were of the transition type (60.0%). This rate was significantly lower than that in Chile (12/12, P<0.05). In addition, three mutations were of the CpG transition type (15.0%), which is a feature of endogenous mutation. All three were found in the hot spot region of the TP53 gene. In contrast, G:C to T:A transversion was found in Bolivia, suggesting the presence of exogenous carcinogens. Our findings suggest that the development of GBC in Bolivia is associated with both exogenous carcinogens and endogenous mechanisms. The identification of an environmental risk factor for GBC is needed to confirm these findings.

• 대한임상검사과학회지
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• 제53권1호
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• pp.41-48
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• 2021

Essential thrombocythemia (ET) is a clonal bone marrow stem cell disorder, primarily involving the megakaryocytic lineage. The WHO 2016 guidelines include the molecular detection of JAK2, MPL, and CALR mutations as a major diagnostic criterion for ET. This study aimed to determine the frequency of JAK2 V617F, MPL W515L, and CALR mutations in Iraqi Kurdish patients afflicted with ET, and to analyze their clinical and hematological features. A total of 73 Iraqi Kurdish patients with ET were enrolled as subjects, and analysis was achieved utilizing real-time PCR. The frequency of JAK2 V617F, CALR, and MPL W515L mutations was determined to be 50.7%, 22%, and 16.4%, respectively. No statistically significant difference was obtained when considering the age and gender among different genotypes. The JAK2 V617F mutated patients had significantly higher white blood cell counts and hemoglobin levels than the CALR-positive patients (P-value=0.000, 0.007, respectively), MPL W515L-positive patients (P-value=0.000, 0.000, respectively), and triple negative patients (P-value=0.000, 0.000, respectively). Also, the JAK2 V617F mutated patients showed higher platelet count as compared to the MPL W515L-positive patients (P-value=0.02) and triple negative patients (P-value=0.04). Furthermore, significantly lower white blood cell count and hemoglobin levels were associated with CALR positivity (P-value=0.000, 0.01, respectively), MPL W515L-positivity (P-value=0.001, 0.000, respectively), and triple negativity (P-value=0.000, 0.000, respectively), as compared to patients with combined mutations. In conclusion, apart from a relatively high frequency of MPL W515L mutation, our data is comparable to earlier reports, and highlights the importance of genotyping the JAK2 V617F, MPL W515L, and CALR mutations for accurate diagnosis of patients with ET.

• Journal of Preventive Medicine and Public Health
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• 제31권1호
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• pp.15-26
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• 1998

p53 돌연변이 여부에 따른 유방암의 위험 인자를 찾아내고, p53 유전자 돌연변이가 유방암 발생에 관여하는 기전을 알아보기 위하여, 1993년 1월부터 1994년 11월 사이에 서울중앙병원에서 유방암으로 진단 받고 수술을 받은 환자 81명과, 이들과 연령, 거주 지역,교육 수준, 그리고 폐경 상태 등에 따라 1:1 혹은 1:2로 짝지은 대조군 121명을 대상으로, 임신력과 중요 영양소 및 총 칼로리 섭취량, 그리고 기타 유방암 관련 요인, p53 유전자 돌연변이 여부, 돌연변이 유형 등을 확인하여 다음과 같은 결과를 얻었다. 유방암 환자 81명중에 돌연변이가 관찰된 예는 25예(30.9%)였다. 이중에서 염기 치환이 20예(24.63%)로서 전이와 변위가 각각 10예(12.3%)였다. 전이 중에는 'C to T' 전이가 8예(9.9%), 'G to A'와 'A to G'는 각각 1예(1.2%)에 불과하였다. 변위는 'C to G'와 'G to T'가 각각 4예(4.9%)였고,'A to T'와 'T to A'가 각각 (1.2%)였다. 삽입과 탈락은 각각 4예(4.9%)와 1예(1.2%)였다. 전체 환자군과 전체 대조군 사이의 비교에서 분만횟수가 증가할수록 유방암의 대응비는 유의하게 감소하는 경향을 보였으며, 열량, 지방 및 단백질의 섭취량이 증가할수록 유방암의 위험도가 유의하게 증가하였다. p53 돌연변이 양성 환자군과 그 대조군 사이의 비교에서 지방과 단백질의 섭취량이 증가할수록 유방암의 위험도가 증가하였으나, 분만횟수증가는 유방암 위험도에 유의한 영향을 미치지 않았다. p53의 돌연변이가 확인되지 않은 경우에도 분만횟수 증가는 유의하지 않았으며, 식이요인 중에는 단백질만이 의미 있는 위험인자로 나타났다. 식이요인에 의한 유방암의 위험도 증가는 p53돌연변이가 존재하는 경우에 특히 두드러지게 나타났다. 이러한 결과는 식이 요인이나 그와 관련된 내분비적 요인에 의하여 p53 변이가 유발되고 이 변이가 유방 세포 암발생의 첫 단계로 작용하거나, 혹은 p53의 변이가 다른 유전자의 변이에 뒤 이어서 발생하는 촉진인자(promoter)로 작용할 수 있음을 시사하는 소견이다.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제26권4호
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• pp.337-344
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• 2000

본 연구에서는 MSI와 구강암과의 상관관계를 규명하기 위하여 17례의 구강암에 대하여 12종류의 marker를 이용하여 MSI 빈도를 조사하였으며, 동시에 p53단백의 과발현과 유전자 돌연변이 양상에 대해서도 알아보았다. 그 결과 4종류 이상의 marker에 대해서 MSI가 나타나는 widespread MSI의 경우 임상병리학적으로 뚜렷한 특징이 없었다. 또한 흡연과 MSI 빈도간에도 연관성이 없었으나 흡연은 p53 유전자의 돌연변이를 증가시켜 암화과정을 촉진하는 작용을 하는 것으로 나타났다.

• Archives of Pharmacal Research
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• 제25권2호
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• pp.208-213
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• 2002

The human polyomavirus JC virus is the etiologic agent of progressive multifocal leukoencephalopathy (PML). As the JC virus early promoter directs cell-specific expression of the viral replication factor large T antigen, transcriptional regulation constitutes a major mechanism of glial tropism in PML. It has been demonstrated that SV4O or JC virus large T antigen interacts with p53 protein and regulates many viral and cellular genes. In this study we founts that p53 represses the JC virus early promoter in both glial and nonglial cells To identify the cis-regulatory elements responsible for p53-mediated repression, deletional and site-directed mutational analyses were performed . Deletion of the enhancer region diminished p53-mediated transcriptional repression. However, point mutations of several transcription factor binding sites in the basal promoter region did not produce any significant changes. In support of this observation, when the enhancer was fused to a heterologous promoter, p53 red reduced the promoter activity about three fold. These results indicate that the enhancer region is important for tole repression of JC virus transcription by p53. Furthermore, coexpression of JC virus T antigen with a p53 protein abolished p53-mediated repression of the JC virus early promoter in non-glial cells, but not in glial cells. This finding suggests that T antigen interacts with p53 and regulates JC virus transcription in a cell-specific manner.