The HLRCC tumors had significant methylation-associated mRNA downregulation of OVOL1, although OVOL2 had no methylation or downregulation, and this correlated with the expected increased expression of MYC and the markers of EMT including ZEB1, a transcriptional target of OVOL1 (Fig 3). Here, OVOL2 is linked to hereditary leiomyomatosis and renal cell cancer.