MYCN-amplified medulloblastoma

Focal high-level amplifications of MYC (or MYCC) define a subset of high-risk medulloblastoma patients.

Transcriptomic analysis revealed SHH-driven tumorigenesis in a subset of MYCN-MBs indicating a biological dichotomy of MYCN-MB.

Activation of SHH is accompanied by variant-specific cytogenetic aberrations including deletion of 9q in SHH tumors.

Non-SHH MB are associated with gain of 7q and isochromosome 17q/17q gain.

Among clinically relevant variables, SHH subtype and 10q loss for non-SHH tumors comprised the most powerful markers of favorable prognosis in MYCN-MB.

Based on the enrichment of MYCN and GLI2 amplifications in SHH-driven medulloblastoma, amplification of these downstream signaling intermediates should be taken into account before a patient is enrolled into a clinical trial using a smoothened inhibitor.

Open references

 Rapid diagnosis of medulloblastoma molecular subgroups. Schwalbe EC, Lindsey JC, Straughton D, Hogg TL, Cole M, Megahed H, Ryan SL, Lusher ME, Taylor MD, Gilbertson RJ, Ellison DW, Bailey S, Clifford SC. Clin Cancer Res. 2011 Apr 1;17(7):1883-94. PMID: #21325292# (Free)

References

 Biological and clinical heterogeneity of MYCN-amplified medulloblastoma. Korshunov A, Remke M, Kool M, Hielscher T, Northcott PA, Williamson D, Pfaff E, Witt H, Jones DT, Ryzhova M, Cho YJ, Wittmann A, Benner A, Weiss WA, von Deimling A, Scheurlen W, Kulozik AE, Clifford SC, Peter Collins V, Westermann F, Taylor MD, Lichter P, Pfister SM. Acta Neuropathol. 2012 Apr;123(4):515-27. doi: 10.1007/s00401-011-0918-8. PMID: #22160402#

 Integrated genomics identifies five medulloblastoma subtypes with distinct genetic profiles, pathway signatures and clinicopathological features. Kool M, Koster J, Bunt J, Hasselt NE, Lakeman A, van Sluis P, Troost D, Meeteren NS, Caron HN, Cloos J, Mrsić A, Ylstra B, Grajkowska W, Hartmann W, Pietsch T, Ellison D, Clifford SC, Versteeg R. PLoS One. 2008 Aug 28;3(8):e3088. PMID: #18769486# [Free]

 Surace C, Pedeutour F, Trombetta D, Burel-Vandenbos F, Rocchi M, Storlazzi CT. Episomal amplification of MYCN in a case of medulloblastoma. Virchows Arch. 2008 Feb 20; PMID: #18286303#