JoVE - Journal of Visualized Experiments
JoVE Visualize
Contact Us

Pitfalls in the evaluation of CDKN2A copy number status in meningioma

  • 0Institute of Neuropathology, DGNN Brain Tumor Reference Center, University Hospital Bonn, Bonn, Germany. valentina.zschernack@ukbonn.de.
Journal of Neuro-Oncology +

|

April 14, 2025

|

April 14, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Accurate molecular testing for CDKN2A deletions is crucial for grading anaplastic meningiomas. MTAP immunohistochemistry (IHC) can be unreliable, necessitating molecular analysis for precise diagnosis.

Area Of Science

  • Neuro-oncology
  • Molecular Pathology
  • Cancer Genomics

Background

  • Anaplastic meningiomas, the most common primary intracranial tumors, carry a poor prognosis.
  • CDKN2A deletions are critical markers of malignancy, integrated into the 2021 WHO classification.
  • p16 and MTAP immunohistochemistry (IHC) are used to detect CDKN2A loss but have accuracy limitations.

Purpose Of The Study

  • To evaluate the concordance between molecular methods and protein expression (p16, MTAP) for assessing CDKN2A loss.
  • To determine the reliability of IHC markers for classifying high-grade meningiomas.
  • To highlight the importance of accurate molecular testing for therapeutic implications.

Main Methods

  • Analysis of nine anaplastic meningiomas.
  • Comparison of DNA methylation profiling, MIP analysis, NGS, and FISH with p16 and MTAP IHC.
  • Assessment of CDKN2A deletion status using various molecular techniques.

Main Results

  • p16 loss showed good correlation with CDKN2A deletions.
  • MTAP protein expression persisted in three cases with homozygous CDKN2A deletions due to hemizygous deletion.
  • A FISH probe for both genes yielded misleading results.

Conclusions

  • MTAP IHC is unreliable as a sole surrogate for CDKN2A loss in anaplastic meningioma.
  • Quantitative copy-number analysis (e.g., chromosomal arrays) precisely determines CDKN2A deletions.
  • Negative p16/MTAP IHC in high-grade meningiomas warrants molecular analysis for CDKN2A deletions.

Related Concept Videos

Comparing Copy Number Variations and SNPs 02:26

16.8K

Sequencing of the human genome has opened up several best-kept secrets of the genome. Scientists have identified thousands of genome variations that exist within a population. These variations can be a single nucleotide or a larger chromosomal variation.
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...

Mismatch Repair 01:20

4.7K

Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...

Abnormal Proliferation 02:23

4.4K

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...