The Molecular Landscape of Primary CNS Lymphomas (PCNSLs) in Children and Young Adults

Zhi-Feng Shi ^1,2, Kay Ka-Wai Li ³, Anthony Pak-Yin Liu ^4,5

⁰Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China.

Cancers +

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May 11, 2024

View abstract on PubMed

Summary

Pediatric primary CNS lymphomas (PCNSLs) show distinct molecular profiles compared to adult cases. Gene rearrangements and CDKN2A homozygous deletions were less common and associated with different outcomes in young patients.

Area Of Science

Oncology
Molecular Biology
Neurology

Background

Pediatric primary CNS lymphomas (PCNSLs) are rare and poorly understood, especially regarding their molecular characteristics.
Adult PCNSLs have established molecular features, but these are not well-defined in younger populations.

Purpose Of The Study

To investigate the molecular features of PCNSLs in pediatric and young adult patients.
To compare these findings with those in older adult PCNSLs and assess their impact on prognosis.

Main Methods

Analysis of gene rearrangements (BCl2, BCL6, CCND1, IRF4, IGH, IGL, IGK, MYC) and homozygous deletions (CDKN2A, HLA) using fluorescence in situ hybridization (FISH).
Whole exome sequencing (WES), panel target sequencing, or Sanger sequencing for molecular analysis.
Evaluation of overall survival (OS) and immunophenotypic characteristics (GCB).

Main Results

Only 5% of young patients exhibited gene rearrangements, which were associated with older age (p=0.029).
CDKN2A homozygous deletions were significantly linked to shorter overall survival (p<0.001).
MYD88 and CARD11 mutations were observed in a subset of cases (32% and 33%, respectively), without significant prognostic impact. The majority of cases were GCB immunophenotype (61%).

Conclusions

Pediatric and young adult PCNSLs display molecular profiles that largely differ from those found in older adults.
Specific molecular alterations common in adult PCNSLs are infrequently detected in younger individuals.
These molecular differences may contribute to the distinct clinical behavior observed in young patients with PCNSLs.

Keywords:

CNS lymphoma children young adult