Posterior fossa ependymoma: current insights.
BACKGROUND
Ependymoma is the third most common malignant tumor of the posterior fossa and is a major cause of neurological morbidity and mortality in children. Current treatments, particularly surgery and external beam irradiation result in relatively poor outcomes with significant neurological and cognitive sequelae from treatment. Historical approaches have considered all ependymomas as similar entities based on their morphological appearance.


RESULTS
Recent advances in genomics and epigenetics have revealed, however, that ependymomas from different CNS locations represent distinct entities. Moreover, ependymoma of the posterior fossa, the most common location in children, is actually comprised of two distinct molecular variants. These two variants have marked differences in demographics, transcriptomes, structure, methylation patterns, and clinical outcomes. This allows for the development of new biology-based clinical risk stratification, which can both prioritize patients for de-escalation of therapy and identify those who will benefit from novel therapeutic strategies. Indeed, the identification of these two variants allows an opportunity for robust preclinical modeling for development of novel therapeutic strategies.


CONCLUSIONS
Herein, we have summarized our current clinical approach to diagnosis and treatment of posterior fossa ependymoma, recent advances in understanding the biology of posterior fossa ependymoma and how these new insights can be translated into the clinic to form the basis of the next generation of clinical trials.
Developmental and Stem Cell Biology Program, Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G1X8, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
Yuan Y
YY
Thompson
Developmental and Stem Cell Biology Program, Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G1X8, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.|Division of Hematology/Oncology, Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G1X8, Canada.
Vijay
V
Ramaswamy
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
Phedias
P
Diamandis
Developmental and Stem Cell Biology Program, Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G1X8, Canada.
Craig
C
Daniels
Developmental and Stem Cell Biology Program, Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G1X8, Canada. mdtaylor@sickkids.ca.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada. mdtaylor@sickkids.ca.|Division of Neurosurgery, Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G1X8, Canada. mdtaylor@sickkids.ca.
Michael D
MD
Taylor
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003388:Cranial Fossa, Posterior / Q000473:pathology; D004806:Ependymoma / Q000473:pathology* / Q000601:surgery*; D057890:Epigenomics; D005260:Female; D023281:Genomics; D006801:Humans; D015192:Infratentorial Neoplasms / Q000473:pathology* / Q000601:surgery*; D008297:Male; D055815:Young Adult
Ependymoma; Genomics; Posterior fossa