Artikel
MYCN-amplified medulloblastomas: biological and clinical heterogeneity
Suche in Medline nach
Autoren
Veröffentlicht: | 11. September 2012 |
---|
Gliederung
Text
Amplifications of MYC define a subset of high-risk medulloblastoma patients. However, the prognostic role of MYCN oncogene amplification remains unresolved. We aimed to evaluate the prognostic value of this alteration in 67 medulloblastomas with MYCN amplification (MYCN-MB). Twenty-one tumors were examined using gene expression profiling and array-CGH, whereas for 46 MYCN-MB immunohistochemical analysis and FISH were performed.
Considerable heterogeneity within MYCN-MB in terms of genetics, tumor biology, and clinical outcome was found. Transcriptomic analysis revealed SHH-driven tumorigenesis in a subset of MYCN-MBs indicating a biological dichotomy of MYCN-MB. Activation of SHH was accompanied by variant-specific cytogenetic aberrations including deletion of 9q. Non-SHH MYCN-MB were associated with gain of 7q and isochromosome 17q. Among clinically relevant variables, SHH signature (detected by expression profiling and/or immunohistochemistry) and 10q loss for non-SHH tumors comprised the most powerful markers of favorable prognosis in MYCN-MB.
Thus assessment of molecular signature and 10q copy-number status may improve risk stratification and delineate MYCN-MB with the same dismal prognosis as MYC amplified tumors. Furthermore, based on the enrichment of MYCN and GLI2 co-amplifications in SHH-driven medulloblastoma, high-level gains of these downstream signaling intermediates should be taken into account before a patient is enrolled into a clinical trial using SMO inhibitors.