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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
What 20 years of research has taught us about the TP53 p.R337H mutation
Emilia Modolo Pinto1, Gerard P Zambetti1
1Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee.
Abstract:
The p53 tumor suppressor transcriptionally regulates a myriad of genes involved in cell cycle control, DNA repair, cell survival, and cell metabolism and represents one of the most well-studied inhibitors of tumorigenesis. Since the discovery of TP53 in 1979, somatic mutations have been shown to be extremely common; more than 50% of human cancers carry loss-of-function mutations in TP53. Inherited or germline TP53 mutations are rare and are involved in complex hereditary cancer predisposition disorders, and affected family members can develop diverse tumor types and multiple primary cancers at young ages. In Brazil, a fascinating history of p53 and cancer predisposition began in the year 2000 with identification of the TP53 p.R337H mutation in close association with the development of adrenocortical tumors. In these past 20 years, much has been learned about the genetics and biochemistry of this mutation, which is widespread in Brazil because of a founder effect. This review highlights the contributions of TP53 p.R337H research over the last 20 years, the findings of which have sparked passionate debate among researchers worldwide, to understanding cancer predisposition in Brazilian individuals and families.
Insights
The TP53 p.R337H mutation, common in Brazil due to a founder effect, is linked to adrenocortical tumors and other cancers. Research over 20 years has significantly advanced understanding of this cancer predisposition.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- The p53 tumor suppressor is a key inhibitor of tumorigenesis, regulating genes for cell cycle, DNA repair, survival, and metabolism.
- TP53 mutations are frequent in human cancers (over 50%), while germline mutations are rare, causing hereditary cancer predisposition syndromes.
- In Brazil, the TP53 p.R337H mutation, identified in 2000, is associated with adrenocortical tumors and has a significant founder effect.
Purpose of the Study:
- To review the contributions of TP53 p.R337H research over the past 20 years.
- To highlight advancements in understanding cancer predisposition in Brazilian individuals and families related to this specific mutation.
Main Methods:
- Literature review of studies on TP53 p.R337H.
- Analysis of genetic and biochemical findings related to the mutation.
- Examination of cancer predisposition in Brazilian populations.
Main Results:
- The TP53 p.R337H mutation is widespread in Brazil, linked to adrenocortical tumors and other cancers.
- Twenty years of research have elucidated the genetics and biochemistry of this mutation.
- Findings have stimulated global scientific debate on cancer predisposition.
Conclusions:
- TP53 p.R337H research has substantially improved the understanding of cancer predisposition in Brazil.
- The mutation's prevalence and associated cancers underscore the importance of genetic studies in specific populations.
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