The DNA methylome of pediatric brain tumors appears shaped by structural variation and predicts survival.

Of the 677 genes with SV-expression associations at p < 0.01 for 1 Mb region (linear model adjusting for covariates) across the CBTN cohort, 126 were also associated with patient overall survival ( p < 0.05, Cox incorporating histologic type) in the same direction (e.g., genes both higher with SV breakpoints and higher in patients with worse survival), representing a highly significant overlap ( p < 1E-9, chi-squared test, Fig. 5a and Supplementary Data 7 ).

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However, highly significant numbers of the nominally significant genes from the earlier cohort overlapped with the significant genes from the additional cohort benefitting from increased tumor numbers and power (Supplementary Fig. 5b and Supplementary Data 8 ), a further indication of these expression differences being reproducible and robust.

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