Genomic landscape and molecular subtypes of primary central nervous system lymphoma

Category	Detail
Condition	Primary central nervous system lymphoma (PCNSL), a rare extranodal non-Hodgkin lymphoma subtype
Key Mechanisms	Genetically heterogeneous disorder with low-frequency mutations, somatic copy number alterations, and structural variants; distinct molecular subtypes based on single-nucleotide variations
Target Population	Patients with newly diagnosed PCNSL, including Chinese cohorts
Care Setting	Tertiary care cancer centers with access to genomic sequencing and HD-MTX-based immunochemotherapy

PCNSL is molecularly distinct from systemic diffuse large B-cell lymphoma (DLBCL) and exhibits unique genomic heterogeneity.
Three molecular subtypes of PCNSL were defined based on single-nucleotide variations, each associated with distinct clinical outcomes.
Current standard treatment involves high-dose methotrexate-based combination immunochemotherapy, with potential for subtype-based targeted therapies.

Diagnose PCNSL based on WHO criteria with histopathological confirmation by at least two pathologists.
Exclude systemic lymphoma via FDG PET/CT and bone marrow aspiration per International PCNSL Collaborative Group and European Association of Neuro-Oncology guidelines.
Exclude ocular involvement before diagnosis.

Treat PCNSL patients with high-dose methotrexate (HD-MTX)-based combination immunochemotherapy regimens (e.g., HD-MTX with idarubicin, rituximab, or BTK inhibitors).
Consider whole-brain radiation therapy or stem cell transplantation as consolidation therapy.

Perform long-term clinical follow-up post-treatment to monitor disease status and outcomes.

Recognize that PCNSL has an unfavorable prognosis despite standard HD-MTX-based regimens.
Molecular heterogeneity may impact treatment response and prognosis.

140 newly diagnosed PCNSL patients from multiple Chinese tertiary centers, plus an external cohort of 36 Chinese PCNSL patients.

All patients received HD-MTX-based combination immunochemotherapy; molecular subtyping may guide future precision oncology approaches.

Collect paired tumor and blood samples promptly and store appropriately (snap-frozen at -80°C or FFPE with controlled shipment) to ensure DNA integrity for genomic analysis.
Use whole-exome sequencing (WES) and whole-genome sequencing (WGS) for comprehensive genomic profiling.
Integrate molecular subtype classification into clinical decision-making to tailor therapies and improve prognosis.
Exclude patients with prior steroid treatment to avoid confounding molecular analyses.

Clinical Scorecard: Molecular Subtypes and Genomic Characteristics of Primary Central Nervous System Lymphoma