Analysis of the role of mutations in the KMT2D histone lysine methyltransferase in bladder cancer

Histone lysine methyltransferases ( HMT ) comprise a subclass of epigenetic regulators; dysregulation of these enzymes affects gene expression, which may lead to tumorigenesis. Here, we performed an integrated analysis of 50 HMT s in bladder cancer and found intrinsic links between copy number alterations, mutations, gene expression levels, and clinical outcomes. Through integrative analysis, we identified six HMT genes ( PRDM 9 , ASH 1L , SETD 3 , SETD 5 , WHSC 1L1 , and KMT 2D ) that may play a key role in the development and progression of bladder cancer. Of these six HMT s, histone lysine N ‐methyltransferase 2D ( KMT2D ) exhibited the highest mutation rate in bladder cancer. Our comparison of the mRNA and mi RNA expression profiles of mutated and wild‐type KMT 2D suggested that two signaling pathways ( FOX 1–miR‐1224‐5p– DLK 1 and HIF / GATA 5–miR‐133a‐3p– DRD 5) may mediate the tumor suppressive effect of the KMT 2D mutation. In summary, our findings indicate that mutations in HMT genes, especially KMT 2D mutation, may play a role in the development of bladder cancer.