WNT-activated embryonal tumors of the pineal region: ectopic medulloblastomas or a novel pineoblastoma subgroup?

Excerpt

Pineoblastoma (PB) is a CNS embryonal tumor of childhood with propensity to metastasize and a 5-year overall survival of 61% [5]. Originating from the pineal gland, PBs carry molecular profiles distinct from medulloblastomas (MBs), the most frequent embryonal tumors that by definition are located in the posterior fossa [2]. Based on methylation profiling, independent studies have identified biologically and clinically relevant subgroups in PB, driven by discrete genomic alterations [4, 5, 7]. In addition to tumors comprising these bona fide PB subgroups, rare outliers have anecdotally been described. Here, we present a multi-institutional series of patients (n = 7) with WNT-activated embryonal tumors epicentered at the pineal region, including three unreported patients and four that had been briefly described [4, 5, 8]. Findings from DNA methylation array, tumor sequencing, and immunohistochemistry were reported. Clustering and copy-number analysis of methylation profiles were performed as previously described, adopting a radiographically and molecularly verified in-house cohort of MB and PB as reference [5]. …