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Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Acylcarnitine Profiling in Meningiomas with Different NF2 Mutation Statuses
Joanna Bogusiewicz1, Jacek Furtak2,3, Marcin Birski3
1Department of Pharmacodynamics and Molecular Pharmacology, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, 85-089 Bydgoszcz, Poland.
Abstract:
The mutation in NF2 is the most common alteration associated with meningioma oncogenesis, and it is related to the loss of a suppressing protein called merlin. At the same time, alterations in energy production are visible in cancer cells, where increased demands for energy are observed. Fatty acid oxidation could be one of the ways cancer cells obtain energy. This metabolic pathway uses the acylcarnitine shuttle system, which is responsible for the acylation of fatty acids and their transport through the mitochondria. Therefore, this study aimed to profile acylcarnitines with short, medium, and long acyl chain lengths in meningiomas to assess their changes in tumors with different NF2 mutation statuses. For the analysis, solid-phase microextraction (SPME) coupled with liquid chromatography-high-resolution mass spectrometry (LC-HRMS) was used. The presented sampling method enabled less invasive and easy collection of the analytes from the studied lesions, which can be crucial for future analysis of potential biomarkers in the surgery room. It was observed that higher levels of these analytes characterized meningiomas with NF2 mutations. Moreover, the increased energy consumption and elevated levels of acylcarnitines show that these analytes can be considered markers of increased fatty acid oxidation in NF2 mutated cells.
Insights
Meningiomas with NF2 mutations show higher levels of acylcarnitines, indicating increased fatty acid oxidation for energy. This finding suggests acylcarnitines may serve as biomarkers for NF2-mutated tumors.
Area of Science:
- Oncology
- Biochemistry
- Metabolomics
Background:
- NF2 gene mutations are central to meningioma development, leading to merlin protein loss.
- Cancer cells exhibit altered energy metabolism, with increased reliance on pathways like fatty acid oxidation.
- The acylcarnitine shuttle system is crucial for transporting fatty acids into mitochondria for oxidation.
Purpose of the Study:
- To profile acylcarnitines (short, medium, long chain) in meningiomas.
- To evaluate acylcarnitine changes in relation to NF2 mutation status.
- To explore acylcarnitines as potential biomarkers for altered cell metabolism.
Main Methods:
- Solid-phase microextraction (SPME) for sample collection.
- Liquid chromatography-high-resolution mass spectrometry (LC-HRMS) for acylcarnitine analysis.
- Profiling of acylcarnitines across different chain lengths.
Main Results:
- Elevated levels of acylcarnitines were observed in meningiomas with NF2 mutations.
- Increased acylcarnitine levels correlate with heightened fatty acid oxidation.
- The SPME method offers a less invasive approach for analyte collection.
Conclusions:
- Acylcarnitines are elevated in NF2-mutated meningiomas, reflecting increased fatty acid oxidation.
- These acylcarnitines can be considered potential biomarkers for increased energy metabolism in NF2-mutated cancer cells.
- The developed sampling technique is suitable for potential intraoperative biomarker analysis.

