Epco-28. The Molecular Landscape and Its Prognostic Implications in Adult Papillary Tumors of the Pineal Region - A Multicenter Youngnoa Investigation

Papillary tumors of the pineal region (PTPR) are rare central nervous system (CNS) neoplasms with variable clinical behavior, where robust prognostic biomarkers for adult patients remain elusive. Here, we performed comprehensive DNA methylation and copy number variation (CNV) analyses on 64 adult PTPRs from newly assembled (n=21) and public (n=43) cohorts to validate molecular subtypes and refine prognostic stratification. We confirmed distinct PTPR-A and PTPR-B molecular profiles, with PTPR-B showing a non-significant trend towards poorer progression-free survival (PFS) in adult-specific analyses. Exploratory comparisons between Favorable (PFS > 50 months) and Unfavorable (PFS < 50 months) Prognosis Groups consistently revealed hypermethylation of G protein-coupled receptor (GPCR) signaling pathway gene promoters in Unfavorable PTPR across independent cohorts. Unfavorable cases also showed preliminary evidence of accelerated epigenetic aging (epiTOC2/3). Integrative Unsupervised Uniform Manifold Approximation and Projection (UMAP) analysis positioned PTPR-B near WNT-medulloblastoma. Our findings delineate the adult PTPR molecular landscape, suggest novel prognostic avenues beyond the A/B classification implicating GPCR signaling and epigenetic deregulation, and underscore the critical need for larger collaborative studies to develop targeted therapies for this rare tumor.