Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

Loss of Tumor Suppressor Gene Functions

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...

In-vitro Mutagenesis

In-vitro Mutagenesis

To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by

Same author

Cell death-induced release of the pro-aging protein acyl CoA binding protein (ACBP) into the circulation.

Cell death and differentiation·2026

Same author

Low-penetrance TP53 variants are mainly hypomorphic: an underestimated issue with high clinical significance.

NPJ genomic medicine·2026

Same author

Acyl-CoA-binding protein (ACBP): a poor-prognosis biomarker in sepsis and a target for disease mitigation.

Signal transduction and targeted therapy·2026

Same author

Neutralization of acyl-CoA-binding protein attenuates glucocorticoid-mediated suppression of cancer immunosurveillance.

Proceedings of the National Academy of Sciences of the United States of America·2026

Same author

Urinary miR-191-5p levels are significantly reduced after radical prostatectomy in patients with prostate cancer.

Cancer cell international·2026

Same author

Association of immune relevant single nucleotide polymorphisms with ALK-positive anaplastic large cell lymphoma presentation and outcome: results of the immuno ALCL study.

Journal of translational medicine·2025

Search research articles

Related Experiment Video

Updated: Nov 29, 2025

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

Comprehensive assessment of TP53 loss of function using multiple combinatorial mutagenesis libraries.

Vincent Carbonnier¹, Bernard Leroy², Shai Rosenberg^3,4

¹Centre de Recherche des Cordeliers, INSERM, U1138, Paris, France.

Scientific Reports

|November 24, 2020

Summary

Accurately predicting TP53 variant pathogenicity is crucial for cancer diagnosis. This study integrates functional data from over 10,000 TP53 variants, revealing insights into splicing impacts for improved clinical predictions.

More Related Videos

Integration of Wet and Dry Bench Processes Optimizes Targeted Next-generation Sequencing of Low-quality and Low-quantity Tumor Biopsies

Integration of Wet and Dry Bench Processes Optimizes Targeted Next-generation Sequencing of Low-quality and Low-quantity Tumor Biopsies

Published on: April 11, 2016

Comparative Lesions Analysis Through a Targeted Sequencing Approach

Comparative Lesions Analysis Through a Targeted Sequencing Approach

Published on: November 5, 2019

Related Experiment Videos

Last Updated: Nov 29, 2025

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

Integration of Wet and Dry Bench Processes Optimizes Targeted Next-generation Sequencing of Low-quality and Low-quantity Tumor Biopsies

Integration of Wet and Dry Bench Processes Optimizes Targeted Next-generation Sequencing of Low-quality and Low-quantity Tumor Biopsies

Published on: April 11, 2016

Comparative Lesions Analysis Through a Targeted Sequencing Approach

Comparative Lesions Analysis Through a Targeted Sequencing Approach

Published on: November 5, 2019

Area of Science:

Genetics and Genomics
Cancer Biology
Molecular Diagnostics

Background:

TP53 mutations are critical in human tumors and cancer predisposition, with clinical diagnostic implications.
Accurate prediction of TP53 variant pathogenicity is essential for effective cancer management and genetic counseling.

Purpose of the Study:

To enhance the accuracy of predicting TP53 variant pathogenicity by integrating diverse functional data.
To investigate the impact of TP53 missense mutations on splicing and their contribution to pathogenicity.

Main Methods:

Compiled functional data from three large-scale saturation mutagenesis screening studies (>10,000 TP53 variants).
Utilized correlation analysis and multidimensional scaling to assess agreement between different experimental settings and readouts (yeast/mammalian, transcription/growth arrest/apoptosis).
Analyzed TP53 expression data from The Cancer Genome Atlas to identify splicing defects associated with missense mutations.

Main Results:

Demonstrated excellent agreement between functional data from independent studies and various experimental readouts.
Identified missense mutations in TP53 exons that impair RNA splicing.
Highlighted the necessity of combining protein and RNA prediction for accurate variant pathogenicity assessment.

Conclusions:

Integrating large-scale functional data significantly improves TP53 variant pathogenicity prediction.
Splicing alterations represent an important mechanism by which TP53 variants can impact pathogenicity.
A multi-modal approach combining protein and RNA analysis is vital for precise variant classification in the genomic era.