Molecular Heterogeneity and Cellular Diversity: Implications for Precision Treatment in Medulloblastoma

Abstract

Medulloblastoma, the most common pediatric malignant brain tumor, continues to have a high rate of morbidity and mortality in childhood. Recent advances in cancer genomics, single-cell sequencing, and sophisticated tumor models have revolutionized the characterization and stratification of medulloblastoma. In this review, we discuss heterogeneity associated with four major subgroups of medulloblastoma (WNT, SHH, Group 3, and Group 4) on the molecular and cellular levels, including histological features, genetic and epigenetic alterations, proteomic landscape, cell-of-origin, tumor microenvironment, and therapeutic approaches. The intratumoral molecular heterogeneity and intertumoral cellular diversity clearly underlie the divergent biology and clinical behavior of these lesions and highlight the future role of precision treatment in this devastating brain tumor in children.

Keywords: clinical trials; genetic and epigenetic heterogeneity; intertumoral diversity; medulloblastoma; molecular subgroups.

Figure 1

Relation of histological types and molecular types. The two columns represent histological classification and molecular classification, respectively. Different heights correspond to different ratios. Lines between the columns represent the overlapping classification systems. The broader a line, the more overlapping patients it has. This figure was made based on the date from the reference [12]. CLA: classic medulloblastoma; DN: desmoplastic/nodular medulloblastoma; LCA: large cell/anaplastic medulloblastoma; MBEN: medulloblastoma with extensive nodularity.

Figure 2

Clinical characteristics of MB subgroups. Pie chart illustrating the frequency, age, gender, and clinical features of the four subgroups of MB. The figure was made based on data from the following references [10,21,55,56,57].

Figure 3

Distinct subtypes of MB originate from different progenitor cells and developmental stages. The dotted arrow represents developmental process, while the solid arrow represents tumorigenic process. Cells with same color have the same origination. This figure was made based on data from the references [17,18].