Pathological and molecular heterogeneity of medulloblastoma.
OBJECTIVE
The outcome of medulloblastoma patients and the quality of life of survivors can be improved by both novel therapies and a better tumor classification. This review will focus on the pathology and molecular biology of medulloblastoma and its potential to influence risk assignment and future therapy.


RESULTS
A risk stratification system of pediatric medulloblastoma based on a combination of histopathological evaluation and targeted molecular analysis can be outlined. Among the four variants recognized by the 2007 WHO classification, the desmoplastic medulloblastoma and the medulloblastoma with extensive nodularity have significantly better survival with respect to classic medulloblastoma, whereas the large-cell and anaplastic have a worse prognosis. Moreover, 17p loss, MYC amplification/expression, and 1q gain are associated with poor prognosis; in contrast, monosomy 6, mutation of CTNNB1, and trkC expression identify tumors with a favorable outcome. Emerging evidence indicates that the different precursor cell populations that form the cerebellum are susceptible to mutations in signal pathways that regulate their functions; these mutations alter normal development programmes and may result in the formation of distinct variants of medulloblastoma.


CONCLUSIONS
Better understanding of the growth control mechanisms involved in the development and progression of medulloblastoma will allow improved therapeutic stratification of patients using existing adjuvant therapy as well as the development of new therapeutic approaches.
Department of Experimental Medicine, University Sapienza of Rome, Rome, Italy.
Alberto
A
Gulino
Antonietta
A
Arcella
Felice
F
Giangaspero
D000293:Adolescent; D001932:Brain Neoplasms / Q000188:drug therapy*; D002531:Cerebellum / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D015972:Gene Expression Regulation, Neoplastic; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008527:Medulloblastoma / Q000188:drug therapy*; D011788:Quality of Life; D051880:Receptors, Notch / Q000378:metabolism; D012306:Risk; D016896:Treatment Outcome; D051153:Wnt Proteins / Q000378:metabolism
D053823:Hedgehog Proteins; D051880:Receptors, Notch; D051153:Wnt Proteins