Extended Data Fig. 4: Overexpression of BORIS is seen in resistance models of neuroblastoma and correlates with high-risk disease and a poor outcome.
From: BORIS promotes chromatin regulatory interactions in treatment-resistant cancer cells
a, qRT–PCR and immunoblot analysis of BORIS expression in TAE684-resistant Kelly cell xenograft tumours (1 and 2) and sensitive and resistant cells in culture. The qRT–PCR data are mean ± s.d., n = 4 biological replicates for sensitive and resistant cells (**P = 0.0014; unpaired two-sided t-test) and n = 3 technical replicates for each tumour. b, Bisulfite sequencing of the BORIS promoter in sensitive and resistant cells. Black circles represent methylated cytosine residues in a CpG dinucleotide, empty circles are unmethylated cytosines. The B and C TSSs are indicated by arrows. c, Dose–response curves to TAE684 (left) and immunoblot analysis of BORIS expression (right) in TAE684-sensitive and -resistant SK-N-SH neuroblastoma cells (IC50 values: sensitive, 47.9 nM; resistant, 1,739 nM). d, Dose–response curves to the CDK12 inhibitor, E9 (left) and immunoblot analysis of BORIS expression (right) in sensitive and resistant SK-N-BE(2) neuroblastoma cells (IC50 values: sensitive, 9.5 nM; resistant, 638 nM). Data are mean ± s.d., n = 3 biological replicates for c (left) and d (left). e, Immunohistochemical staining of BORIS expression in primary neuroblastoma tumour samples (representative of four independent experiments). Scale bar, 20 μm. f, Box plots showing correlation of BORIS expression with the indicated parameters in a human neuroblastoma dataset (n = 498; Tumour Neuroblastoma-SEQC-498; R2: Genomics Analysis and Visualization Platform (http://r2.amc.nl)). Box plots are as defined in Fig. 4. P values were determined by two-sided Wilcoxon rank-sum test. g, Kaplan–Meier analysis of overall survival based on BORIS expression in the same dataset as in f (n = 498; two-sided log-rank test with Bonferroni correction). In a, c, d (immunoblots) and b, data are representative of two independent experiments. Sample sizes (n) are depicted in parenthesis for f and g (for gel source data, see Supplementary Fig. 1).
