Figure 1.
Relapsed Medulloblastomas Maintain the Molecular Subgroup but Are Enriched for Multiple High-Risk Clinical and Molecular Features
(A) Consensus clustering (left) and principal component analysis (PCA) (right) of medulloblastoma subgroups at diagnosis and relapse. Consensus molecular subgroups: red, MBSHH; blue, MBWNT; yellow, MBGroup3; green, MBGroup4. In the PCA plot, subgroups assigned at diagnosis are represented by circles, and those assigned at relapse are represented by squares.
(B) Frequency of high-risk disease features within the present paired relapse study cohort sampled at diagnosis and relapse, compared to large historic cohorts sampled at disease diagnosis. p, Fisher’s exact test.
(C) Acquisition of molecular and clinical disease features between diagnosis (top) and relapse (bottom). Left to right: immunohistochemical analysis of p53 protein accumulation; TP53 homozygous missense mutation (Pro152Leu); interphase fluorescence in situ hybridization (iFISH) showing MYCN amplification (green versus centromeric control (red); H&E showing LCA acquisition and magnetic resonance imaging (MRI) showing metastatic spread (arrows indicate tumor site). Scale bars, 50 μM (immunohistochemistry, H&E) or 5 μM (iFISH).