Genetic Variant of p53 Associated With Poor Breast Cancer Survival Interview with:
Maureen E. Murphy, Ph.D.
Program Leader and Professor
Molecular and Cellular Oncogenesis and
Subhasree Basu PhD
Postdoctoral researcher
The Wistar Institute
Philadelphia, PA 19104 What is the background for this study? What are the main findings?

Response: Unlike most other genes that are intimately involved in the cause of cancer, the p53 gene displays considerable genetic variation; in other words, p53 is unusual among cancer genes in that the amino acids in p53 protein can frequently differ amongst different populations and ethnic groups. Additionally, unlike most other tumor suppressor genes, when p53 is mutated in a tumor, as it is in 50% of human cancers, that mutant protein now has a positive function in cancer progression, changing tumor metabolism and promoting tumor metastasis.

In this study, the authors analyze for the first time the impact of a common genetic variant in p53 (single nucleotide polymorphism, or SNP) in the ability of mutant p53 to promote tumor metabolism and metastasis, and they find significant differences. What should readers take away from your report?

Response: A common SNP in p53 that exists predominantly in individuals who live in Northern latitudes actually makes the mutant form of p53 more aggressive in its ability to promote tumor metastasis. In a cohort of breast cancer patients that contain mutant forms of p53, this SNP is associated with poorer overall survival. What recommendations do you have for future research as a result of this work? 

Response: The SNP of mutant p53 that is associated with poor breast cancer survival, called Pro72Arg, alters the metabolism of tumor cells, rendering them more reliant on mitochondria for metabolism. These tumors therefore may be more susceptible to therapy using mitochondrial inhibitors, such as phenformin or metformin, or with other emerging mitochondrial homeostasis inhibitors like Gamitrinib. Is there anything else you would like to add?

Response: Unlike other tumor suppressor genes or oncogenes, there is considerable genetic variation in the p53 gene. Our laboratory is committed to understanding the impact of this genetic variation on cancer risk and prognosis, using both animal and human studies.

No other disclosures 


Genes Dev 2018 Feb 20. doi: 10.1101/gad.309062.117. [Epub ahead of print]

Mutant p53 controls tumor metabolism and metastasis by regulating PGC-1α.
Basu S1, Gnanapradeepan K1,2, Barnoud T1, Kung CP1, Tavecchio M3, Scott J1, Watters A3, Chen Q3, Kossenkov AV4, Murphy ME1.  

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