Pediatric embryonal brain tumors in the molecular era

ABSTRACT

Introduction: Embryonal brain tumors (EBTs) are highly aggressive malignancies predominantly affecting children. They include medulloblastoma (MB), atypical rhabdoid/teratoid tumors (ATRT), pineoblastoma (PB), embryonal tumor multiple rosettes (ETMR)/C19MC-altered tumors, and newly recognized embryonal tumors with FOXR2 activation or BCOR alteration.

Areas covered: This review will provide a comprehensive overview and updated of the literature on each of these EBTs. The evolution from location- and histopathology-based diagnosis to more specific and robust molecular-based classification schemes, as well as treatment modalities, will be discussed.

Expert commentary: The subgrouping of EBTs with multi-omic profiling has had important implications for risk stratification and discovery of targetable driver pathways. However, these innovations are unlikely to significantly improve survival among high-risk patients until robust preclinical studies are conducted, followed by validation in biology-informed clinical trials.

KEYWORDS:

• Atypical teratoid rhabdoid tumor ATRT
• C19MC-altered tumor
• embryonal tumor multiple rosettes ETMR
• medulloblastoma
• pineoblastoma

Article highlights

• EBTs are aggressive malignancies primarily seen in children.

• EBTs include entities such as medulloblastoma, ATRT, pineoblastoma, ETMR/C19MC-altered tumors, and embryonal tumors with FOXR2 activation or BCOR alteration.

• Diagnosis and treatment of these entities are evolving from being based on location/histopathology towards more recently established molecular classification schemes.

• Specific molecular markers have expanded or enabled the recognition of certain EBTs (loss of SMARCB1/INI1 for ATRTs and alteration of the C19MC amplicon for ETMRs).

• Multi-omic profiling have uncovered subgroups for several types of EBTs with distinct clinical and molecular features.

• These revised classification methods may have an emerging role for risk stratification, but the introduction of much-needed novel targeted therapies is still under evaluation.

Declaration of interest

Bryan Li is funded by the Sick Kids Garron Family Cancer Centre Fellowship. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewers Disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.