Each panel depicts -log10 p-values for the association of the indicated genomic feature with prednisolone LC50, and the aggregated gene-level linear model p-value based on all genomic features is shown for each gene at the top right. Red triangles represent mRNA probes within the gene body, orange diamonds depict copy number variants, blue squares are DNA methylation probes, grey circles SNVs, and purple circles miRNAs within 50kb upstream or downstream of gene region (n=203 patients). (a.)
SMARCA4, a component of the SWI/SNF complex, has been previously linked to glucocorticoid resistance in pediatric ALL19
(b.)
NLRP3 encodes NALP3, an inflammasome component that activates caspase 1, and has been previously associated with ALL resistance to glucocorticoids.15
(c.)
PTTG1IP encodes the pituitary tumor-transforming gene 1 proteininteracting protein that interacts with the proto-oncogene PTTG1 (also known as securin). (d.)
CELSR2 is a G-protein coupled receptor involved in non-canonical Wnt signaling. PTTG1IP and CELSR2 are novel genes from the current study associated with glucocorticoid resistance.