# Molecular and clinical characterization of atypical central neurocytomas: implications for diagnosis and treatment strategies

## TL;DR

This study explores the molecular and clinical features of atypical central neurocytomas to improve diagnosis and treatment strategies.

## Contribution

The study identifies genetic alterations and treatment outcomes in atypical central neurocytomas, offering new insights into their management.

## Key findings

- Complete resection significantly improves survival rates in atypical central neurocytoma patients.
- Genetic alterations in pathways like cAMP, MAPK, and Ras are linked to aggressive tumor behavior.
- Postoperative radiotherapy does not improve outcomes after complete tumor resection.

## Abstract

This study aimed to investigate the histological and molecular characteristics of atypical central neurocytomas (CNs) and evaluate their clinical treatment outcomes, with the aim of identifying reliable biomarkers for differentiation and optimal treatment strategies.

We conducted a retrospective study including 61 patients diagnosed with CNs. Clinical data, neuroimaging, and pathological findings were analyzed. RNA sequencing was performed on tumor tissues to identify differentially expressed genes.

Histological atypia and the Ki-67 index showed no significant impact on progression-free survival (PFS) or overall survival (OS). RNA sequencing identified significant genetic alterations in pathways such as neuroactive ligand–receptor interaction, cAMP, MAPK, and Ras signaling. Differently expressed genes included AMOTL1, PIK3R3, TGFBR1, SMO, COL4A6, MGP, SOX4, IGF2, SLIT1, and CKS2. The five-year OS rate (p = 0.015) and PFS rate (p = 2.00 × 10−6) were significantly higher in the complete resection (CR) group compared to the incomplete resection (IR) group. Postoperative radiotherapy did not affect OS or PFS in the CR group. The five-year PFS rate (p = 3.80 × 10−5) was significantly longer in patients in the CR group who did not receive radiotherapy compared to those in the IR group who did receive radiotherapy. The extent of surgical resection and operative approaches were found to be irrelevant to perioperative complications and dysfunctions at the last follow-up.

CR is crucial for a better prognosis in patients with atypical CNs. Additional radiotherapy after CR offers little benefit. Histological atypia and the Ki-67 index are not effective in distinguishing between atypical and typical CNs. Identified genetic alterations provide insights into the aggressive behavior of atypical CNs, suggesting potential therapeutic targets and underscoring the need for further research to optimize treatment strategies.