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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Evidence for selective expression of the p53 codon 72 polymorphs: implications in cancer development
Mobin M Siddique1, Chowbay Balram, Lucja Fiszer-Maliszewska
1Laboratory of Molecular Carcinogenesis, National Cancer Centre, Singapore.
Summary
The p53 gene
Area of Science:
- Genetics
- Molecular Biology
- Cancer Research
Background:
- The p53 tumor suppressor protein plays a crucial role in preventing cancer.
- Polymorphism at codon 72 of the p53 gene results in arginine (arg) or proline (pro) variants, with debated functional implications in carcinogenesis.
- Ethnic variations in p53 polymorphism expression and their association with cancer susceptibility are not fully understood.
Purpose of the Study:
- To investigate the selective regulation of p53 arginine/proline (arg/pro) polymorph expression in different ethnic populations.
- To determine if p53 polymorph expression differs between healthy individuals and breast cancer patients of Asian and Caucasian descent.
- To explore the potential of p53 polymorph expression status as an indicator of cancer susceptibility.
Main Methods:
- Analysis of p53 gene expression using mRNA from peripheral blood of healthy Chinese (Asian) and Polish (Caucasian) subjects heterozygous for the arg/pro polymorphism.
- Comparison of p53 polymorph expression in healthy individuals versus heterozygote Chinese breast cancer patients.
- Examination of p53 polymorph expression in histologically normal tissues from Chinese breast cancer patients.
Main Results:
- Healthy Asians preferentially expressed the p53 proline (pro) allele, while healthy Caucasians preferentially expressed the arginine (arg) allele.
- Approximately 75% of Chinese breast cancer patients (heterozygotes) preferentially expressed the arg allele, which rarely had somatic mutations.
- Histologically normal tissues from Chinese breast cancer patients showed selective arg allele expression, contrasting with the preferential pro allele expression in healthy Chinese breast tissues.
Conclusions:
- p53 polymorph expression is selectively regulated and varies significantly between different ethnic groups.
- The arginine allele of p53 appears to be activated during breast cancer development in Asian populations.
- The expression status of p53 polymorphs, not just the genotype, may serve as a valuable biomarker for cancer susceptibility.
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