Oncology Scan—Molecular Genotyping of Medulloblastoma: A New Treatment Era
International Journal of Radiation Oncology * Biology * Physics
Medulloblastoma is the most common malignant central nervous system tumor of childhood. The current classification schemes are based primarily on histopathology, with treatment dependent upon risk stratification incorporating clinical factors of age, extent of surgical resection, and metastatic disease. For children more than 3 years of age, the current mainstay of treatment involves maximal surgical resection followed by adjuvant craniospinal irradiation (CSI) and boost, in combination with concurrent and maintenance chemotherapy. Although the poor prognostic impact of additional histopathological factors, such as large-cell variant and diffuse anaplasia, have been recognized, the incorporation of molecular genetic features into treatment strategies has previously been elusive. With advances in molecular genetics, it has now been recognized that medulloblastoma comprises a heterogeneous group of tumors with distinct genomic signatures and associated prognostic implications . Four principal transcriptional subgroups of medulloblastoma are recognized, which include: Wnt, Shh (sonic hedgehog), Group 3, and Group 4 . The Wnt and Shh groups are associated with biomarkers of aberrant signaling pathways that drive tumor initiation, whereas Group 3 and Group 4 are more vaguely defined as the underlying genetic alterations driving clinical outcomes that are less well understood. The identification of underlying biology as a clinical driver provides tremendous opportunities for better therapeutic targeting (eg, Shh inhibitors) and allows re-stratification of prognostic groups beyond the clinical markers in use today.
Original Article: http://www.redjournal.org/article/S0360-3016(13)03677-8/abstract?rss=yes
Júlio Pereira
www.neurocirurgiabr.com
www.linkedin.com/in/juliommais
lattes.cnpq.br/7687651239699170
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