Medulloblastoma—translating discoveries from the bench to the bedside

• Published in: Nature reviews. Clinical oncology Vol. 11; no. 12; pp. 714 - 722
• Main Authors: Gajjar, Amar J., Robinson, Giles W.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.12.2014; Nature Publishing Group
• Subjects: 692/699/67/1922; 692/699/67/2332; 692/699/67/69; 692/700/1720; Adolescent; Brain Neoplasms - pathology; Brain Neoplasms - therapy; Care and treatment; Child; Child, Preschool; Development and progression; Distribution; Gene Expression Profiling; Humans; Infant; Medicine & Public Health; Medulloblastoma; Medulloblastoma - pathology; Medulloblastoma - therapy; Oncology; Prognosis; review-article
• ISSN: 1759-4774; 1759-4782
• DOI: 10.1038/nrclinonc.2014.181

Key Points Medulloblastoma is a malignant brain tumour that occurs predominantly in childhood, but is also seen in infancy and throughout adulthood Although the prognosis of medulloblastoma is favourable with current therapeutic regimens, the heterogeneous nature of this cancer has confounded efforts to substantially improve survival and reduce therapy-related toxicity Advancements in technology and its accessibility have led, through molecular interrogation, to the recognition that medulloblastoma heterogeneity is broadly explained by the existence of four main molecular tumour subtypes Each molecular medulloblastoma subtype, termed Wnt, SHH, group 3, and group 4 medulloblastoma, has unique clinical and molecular characteristics, which influence nearly every facet of the disease, including survival Armed with this knowledge, paediatric oncologists find themselves at an opportune moment to capitalize on these newly elucidated characteristics to improve survival and reduce morbidity by tailoring therapy towards the individual subtypes Medulloblastoma is the most-common form of paediatric brain cancer. Advances in our understanding of the molecular basis of medulloblastoma indicate that it is not a single disease, but a collection of four distinct molecular tumour subtypes. This knowledge has important implications for medulloblastoma research and treatment. In this Review, the characteristic demographic, clinical and genetic features of the four molecular subtypes of medulloblastoma are described, and the implications of molecular distinctions on therapy are discussed. Medulloblastoma is a form of brain cancer that mainly arises during infancy and childhood. Our understanding of this disease has transitioned rapidly; what was once thought of as a single disease entity is now known to be a compendium comprising at least four distinct subtypes of tumour (Wnt, sonic hedgehog [SHH], group 3, and group 4 medulloblastomas) that have characteristic molecular signatures, distinctive clinical features, and are associated with different outcomes. Importantly, medulloblastomas occurring in infants (aged up to 3 years) and adults have unique characteristics, which distinguish the disease from that seen in children aged >3 years. Accordingly, modern treatment approaches in medulloblastoma integrate the molecular and clinical features of the disease to enable provision of the most-effective therapies for each patient, and to reduce long-term sequelae. This Review discusses our current knowledge of medulloblastoma. In particular, we present the genetic and histological features, patient demographics, prognosis, and therapeutic options for each the four molecular tumour subtypes that comprise this disease entity. In addition, the unique features of medulloblastoma in infants and in adults, as compared with childhood and/or adolescent forms, are described.