Choroid plexus tumors (CPTs) are rare neuroepithelial neoplasms arising from the choroid plexus epithelium, displaying significant clinical and molecular heterogeneity. The 2021 WHO classification categorizes CPTs into choroid plexus papillomas (CPP, grade 1), atypical CPP (grade 2), and choroid plexus carcinomas (CPC, grade 3). This study aimed to investigate the molecular alterations in CPTs across age groups, sexes, and histological grades to elucidate their pathogenesis and identify potential therapeutic targets.
We analyzed 58 CPT samples using comprehensive genomic profiling (CGP) with hybrid capture-based DNA sequencing (FoundationOne®CDx). The study was conducted in a CAP/CLIA-accredited laboratory and included histopathological confirmation by board-certified neuropathologists. DNA was extracted from paraffin-embedded samples, and sequencing targeted 236–315 cancer-associated genes. Mutations, amplifications, and deletions were analyzed in relation to patient demographics and tumor grades.
The cohort included 11 CPP (grade 1), 16 atypical CPP (grade 2), and 31 CPC (grade 3) cases, with a median patient age of 11.5 years (range: 1–72 years). CPCs occurred predominantly in younger patients (median age: 3 years) compared to CPPs (median age: 34 years; p<0.01). TP53 mutations were identified in 43.1% of cases, predominantly in CPCs (45.2%) and pediatric patients (median age: 2 years). TERT promoter (TERTp) mutations were exclusive to adults, primarily in CPPs (14.8%) and one CPC (3.2%), with all mutations located at c.-124 bp (C228T). DAXX mutations were found in 8.6% of cases, occurring in both CPC and CPP. Other alterations included PTEN mutations, MYCN amplifications, and CDKN2A/B deletions, predominantly in CPCs. A significant proportion of CPP cases (81.1% grade 1, 68.5% grade 2) lacked identifiable pathogenic mutations.
Our findings reveal age- and grade-dependent genetic differences in CPTs, with pediatric CPCs characterized by TP53 mutations and adult CPPs frequently harboring TERTp mutations. These results underscore the importance of telomere biology, particularly involving TERTp and DAXX, in CPT pathogenesis. The heterogeneity across CPT subtypes highlights the necessity of molecular profiling for accurate diagnosis and prognosis.