Integrative Computational Analysis of TP53 Exon 5-6 Mutations in Oral Cavity, Prostate, and Breast Cancers in a

Mouhamed Mbaye1, Fatimata Mbaye2, Mbacke Sembene2

  • 1Pharmaceutical Biophysics Laboratory, Department of Pharmacy, Faculty of Medicine, Pharmacy and Odontology, Cheikh Anta Diop University, Dakar BP. 5005, Senegal.

Genes
|February 27, 2026
PubMed

Insights

TP53 mutations in Senegalese oral, prostate, and breast cancers show distinct patterns. Exon 6 mutations in prostate and breast cancers may stabilize the TP53 protein, impacting BCL-2 interactions.

Area of Science:

  • Genomics and Bioinformatics
  • Cancer Research
  • Molecular Biology

Background:

  • The tumor suppressor gene TP53 is frequently mutated in human cancers, particularly in its DNA-binding domain.
  • The mutational landscape and functional impact of TP53 variants are understudied in African populations.
  • Understanding TP53 alterations is crucial for cancer research and therapeutic development.

Purpose of the Study:

  • To characterize TP53 mutations in exons 5-6 in oral cavity cancer (OCC), prostate cancer (PC), and breast cancer (BC) in a Senegalese population.
  • To assess the structural effects, functional consequences, and impact on p53-BCL-2 interactions of these TP53 variants.
  • To investigate cancer and exon-specific mutation patterns and their potential oncogenic implications.

Main Methods:

  • Analysis of 78 archived tumor DNA samples from Senegalese patients with OCC, PC, and BC.
  • Variant annotation using COSMIC and dbSNP databases.
  • In silico evaluation of functional impact (PolyPhen-2), structural stability (FoldX), conformational dynamics (ENCoM), and p53-BCL-2 interaction (DDMut-PPI).

Main Results:

  • Breast cancer (BC) showed the highest TP53 mutation frequency; oral cavity cancer (OCC) exhibited greater mutational diversity.
  • Exon 5 mutations were predominantly destabilizing and loss-of-function across cancers; exon 6 mutations in PC and BC (e.g., V217L, V218M) were predicted to stabilize the p53 structure.
  • All analyzed mutations were predicted to stabilize the p53-BCL-2 interaction, with significant conformational dynamics differences observed in PC.

Conclusions:

  • Identified cancer and exon-specific TP53 mutation patterns in a Senegalese population.
  • Exon 6 emerges as a context-dependent hotspot with potential oncogenic roles in PC and BC.
  • The study provides valuable in silico insights into TP53 variant impacts, warranting further experimental investigation.

Related Concept Videos

Cancers Originate from Somatic Mutations in a Single Cell02:21

Cancers Originate from Somatic Mutations in a Single Cell

Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
15.1K
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
7.4K
Tumor Progression02:07

Tumor Progression

Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
7.6K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
9.9K