Different impacts of TP53 mutations on cell cycle-related gene expression among cancer types

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• TP53 mutations are crucial in cancer development and progression.
• While most TP53 mutations inactivate p53, some gain-of-function (GOF) mutations acquire novel oncogenic roles.
• The impact of TP53 mutations on the p53 signaling pathway's gene expression profile across diverse cancer types remains uninvestigated.

Purpose of the Study:

• To conduct a cross-cancer type analysis of TP53 mutation effects on gene expression.
• To investigate the influence of TP53 mutations on the p53 signaling pathway's gene expression profile.
• To compare the effects of gain-of-function (GOF) versus non-GOF TP53 mutations.

Main Methods:

• Hierarchical cluster analysis was employed to analyze the gene expression profile of the p53 signaling pathway.
• Twenty-one cancer types were classified into two distinct clusters (A1 and A2) based on expression profiles.
• Gene expression changes, particularly for cell cycle genes and MKI67, were assessed in relation to TP53 mutation status.

Main Results:

• Hierarchical clustering separated 21 cancer types into two main groups (A1 and A2).
• TP53 mutations induced more significant changes in cell cycle-related genes and MKI67 expression within cluster A1 compared to cluster A2.
• No discernible difference was observed in the impact on the p53 signaling pathway's gene expression profile between GOF and non-GOF TP53 mutations.

Conclusions:

• TP53 mutations differentially affect gene expression profiles across cancer types, with distinct impacts observed between hierarchical clusters.
• The magnitude of TP53 mutation-driven gene expression changes, specifically for cell cycle regulators, varies across cancer types.
• Gain-of-function and non-gain-of-function TP53 mutations exhibit similar effects on the overall p53 signaling pathway gene expression profile.