At the third hotspot located on chromosome 13, mutated tumors had on average a 3-fold decrease in SPG20 expression (Wilcoxon P = 0.045, adjusted P = 0.65; Fig. 5g–i). However, only three tumors with expression data were mutated at this hotspot, and the expression change was not significant after correcting for multiple testing. A larger sample size is needed to evaluate if this is a spurious or true correlation. A similar trend in SPG20 expression is observed using the expression data from the SG cohort (Supplementary Fig. 11c). SPG20 is involved in epidermal growth factor receptor trafficking47 and was previously found to be significantly mutated in the exome of esopheagal cancer48.