Related Experiment Video

Updated: Jun 28, 2026

Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells
09:37

Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells

Published on: August 25, 2021

A role for the p53 pathway in the pathology of meningiomas with NF2 loss

ZeNan Chang1, Chin-Lin Guo, Iris Ahronowitz

  • 1Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.

Journal of Neuro-Oncology
|November 1, 2008
PubMed

Insights

The p53 codon 72 polymorphism is linked to higher-grade meningiomas, but only when the neurofibromatosis 2 (NF2) gene is also lost. This suggests p53 influences tumor progression in NF2-inactivated meningiomas.

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • Neurofibromatosis 2 (NF2) gene inactivation occurs in 40-65% of sporadic meningiomas.
  • The role of the p53 tumor suppressor pathway in meningioma development is not fully understood.
  • A p53 codon 72 polymorphism (arginine-to-proline) has been linked to cancer outcomes in other tumor types.

Purpose of the Study:

  • To investigate the association of the p53 codon 72 arginine-to-proline polymorphism with sporadic meningioma initiation and progression.
  • To determine if this polymorphism correlates with tumor grade or NF2 loss of heterozygosity (LOH).

Main Methods:

  • Analysis of p53 codon 72 polymorphism incidence in 92 sporadic meningioma samples.
  • Assessment of tumor histological grade (WHO classification).
  • Determination of NF2 LOH using polymorphic microsatellite markers on chromosome 22q.

Main Results:

  • The Pro72 allele was not found to be selected for in the overall cohort.
  • In meningiomas with NF2 LOH, carriers of Pro72 showed a significantly higher incidence of high-grade tumors (50.0%) compared to those without NF2 LOH (14.3%).
  • The association between Pro72 and high-grade tumors was only significant when NF2 LOH status was considered (OR = 6.0, P = 0.012).

Conclusions:

  • The p53 codon 72 polymorphism may play a role in the progression of meningiomas with concurrent NF2 inactivation.
  • Accounting for NF2 LOH status is crucial for future studies investigating the p53 pathway in meningiomas.
  • This finding highlights the complex interplay between genetic alterations in meningioma pathogenesis.

More Related Videos

Genetic Profiling and Genome-Scale Dropout Screening to Identify Therapeutic Targets in Mouse Models of Malignant Peripheral Nerve Sheath Tumor09:33

Genetic Profiling and Genome-Scale Dropout Screening to Identify Therapeutic Targets in Mouse Models of Malignant Peripheral Nerve Sheath Tumor

Published on: August 25, 2023

Identifying, Diagnosing, and Grading Malignant Peripheral Nerve Sheath Tumors in Genetically Engineered Mouse Models08:57

Identifying, Diagnosing, and Grading Malignant Peripheral Nerve Sheath Tumors in Genetically Engineered Mouse Models

Published on: May 17, 2024

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...