Molecular subgroups of medulloblastoma: the current consensus

TLDR

Medulloblastoma is a leading pediatric cerebellar malignancy whose prognosis traditionally relies on clinical factors and histology, but transcriptional profiling has revealed multiple molecular subgroups with distinct demographics, genetics, and outcomes, prompting a consensus conference to standardize subgroup definitions. The study outlines the current consensus nomenclature for medulloblastoma subgroups and describes their distinguishing features. A consensus conference identified four main medulloblastoma subgroups—Wnt, Shh, Group 3, and Group 4—and characterized their demographic, transcriptional, genetic, and clinical differences.

Abstract

Medulloblastoma, a small blue cell malignancy of the cerebellum, is a major cause of morbidity and mortality in pediatric oncology. Current mechanisms for clinical prognostication and stratification include clinical factors (age, presence of metastases, and extent of resection) as well as histological subgrouping (classic, desmoplastic, and large cell/anaplastic histology). Transcriptional profiling studies of medulloblastoma cohorts from several research groups around the globe have suggested the existence of multiple distinct molecular subgroups that differ in their demographics, transcriptomes, somatic genetic events, and clinical outcomes. Variations in the number, composition, and nature of the subgroups between studies brought about a consensus conference in Boston in the fall of 2010. Discussants at the conference came to a consensus that the evidence supported the existence of four main subgroups of medulloblastoma (Wnt, Shh, Group 3, and Group 4). Participants outlined the demographic, transcriptional, genetic, and clinical differences between the four subgroups. While it is anticipated that the molecular classification of medulloblastoma will continue to evolve and diversify in the future as larger cohorts are studied at greater depth, herein we outline the current consensus nomenclature, and the differences between the medulloblastoma subgroups.