The final selected eight genes were NFE2L2, CSMD1, CREBBP, KALRN, PRUNE2, NRXN1, AKAP9, and FREM2 (Fig. 7a), among which five genes (NFE2L242, CSMD143, CREBBP44, PRUNE245, and AKAP946) had been reported as tumor-suppressing gene or with dominant gain-of-function mutational hotspots in tumors. This evidence concerns the gene FREM2 and neoplasm.