Global DNA methylation differences involving germline structural variation impact gene expression in pediatric brain tumors.

In particular, for each of the genomic region windows 100 kb upstream of the gene, 100 kb downstream of the gene, and within the gene body, we observed highly significant overlap between CGI probes with SV-methylation association ( p < 0.01 by linear model with covariates) and CGI probes for genes with germline SV breakpoint patterns positively associated with pediatric brain tumor patient survival (one-sided Cox p < 0.05, correcting for tumor histologic type, Fig. 6a ).

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The number of nominally significant features expected at a given p -value cutoff (e.g., p < 0.01) due to chance alone, as predicted by probability theory ([total number of features] X [nominal p-value cutoff]), was similarly found when shuffling the 1 Mb germline SV breakpoint and methylation datasets and carrying out the same analyses.

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