Fig. 6: Germline SV breakpoint patterns with differential CGI methylation involving pediatric brain tumor patient survival. | Nature Communications

Fig. 6: Germline SV breakpoint patterns with differential CGI methylation involving pediatric brain tumor patient survival.

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

Fig. 6: Germline SV breakpoint patterns with differential CGI methylation involving pediatric brain tumor patient survival.The alternative text for this image may have been generated using AI.

a Overlapping CGI probes for genes with germline SV breakpoint patterns associated with worse pediatric brain tumor patient survival and CGI probes with SV-methylation association for each of the genomic region windows represented. Enrichment p-values by one-sided Fisher’s exact test. b Combining germline SV data with patient survival data and tumor methylation data across the CBTN patients, 1155 CGI probes had both a positive association between germline SV breakpoints near the gene and worse overall survival and a positive or negative germline SV-methylation association, for the same genomic region window. c Association of the 1155-CGI probe signature from part b with patient survival in the CBTN cohort, based on scoring of the tumor methylation profiles. The direction of each CGI probe in the 1155-CGI probe signature, as applied here to the CBTN methylation dataset, is based on the direction of the germline SV-methylation association. Survival association p-values correct for tumor type. d CGI methylation (purple) and mRNA (orange) levels of POLD4, corresponding to SV breakpoints in the genomic region surrounding the gene. Each point represents a patient. Methylation and mRNA values are respectively normalized to standard deviations from the median (using logit- and log2-transformed values, respectively). e Boxplots of POLD4 CGI methylation (top) and log2 expression (bottom) by germline SV class. P-values versus other by t-test on logit-transformed or log2-transformed values. Boxplots represent 5%, 25%, 50%, 75%, and 95%. f Associations with worse patient survival for POLD4-associated germline SV breakpoint patterns (left), for higher POLD4 CGI methylation (middle), and for lower POLD4 expression (right). POLD4 SV patterns involve breakpoints 412 kb downstream of the gene (as represented in part d). For parts a and b, germline SV breakpoint survival associations by one-sided p < 0.05 by Cox accounting for tumor type (minimum of 10 patients with breakpoint in region), and germline SV-expression associations by p < 0.01 by linear model correcting for covariates. For parts a and b, Cox p-values are one-sided; for part c, Cox p-value is two-sided. For parts c-f, n represents numbers of patients.

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