The first hotspot we identified is located in a CBS on chromosome 6 and has mutations in 12 samples (Fig. 5a–c). The expression of two neighboring genes, CENPQ and MUT, ~1 Mb upstream of this hotspot was significantly elevated in the mutated samples (P = 0.007 and 0.0021 respectively, Benjamini–Hochberg adjusted P = 0.026 and 0.042 respectively, two-sided Wilcoxon rank-sum test; Fig. 5a–c). A similar trend of CENPQ expression was observed using the expression data from the SG cohort (Supplementary Fig. 11a). CENPQ is a subunit of a centromeric complex, and is involved in mitotic progression and chromosomal segregation45. Interestingly, the tumor with the highest expression of CENPQ was mutated at the highly conserved position 9 of the CTCF motif, while the other two tumors were mutated at position 2 of the CTCF motif. This indicates that different mutations in the same hotspot may have different disruptive potentials. However, a formal evaluation of such effects requires a larger set of tumor samples with both CBS mutations and RNA-seq data available.