Loss-of-Imprinting of HM13 Leads to Poor Prognosis in Clear Cell Renal Cell Carcinoma

Genomic imprinting refers to the epigenetic silencing of one of both alleles in a parent-of-origin-specific manner, particularly in genes regulating growth and development. Impaired genomic imprinting leading to the activation of the silenced allele, also called canonical loss-of-imprinting (LOI), is considered an early factor in oncogenesis. As LOI studies in clear cell renal cell carcinoma (ccRCC) are limited to , we performed a genome-wide analysis in 128 kidney normal solid tissue and 240 stage 1 ccRCC samples (TCGA RNA-seq data) to screen for canonical LOI in early oncogenesis. In ccRCC, we observed LOI (adj. = 2.74 × 10 ) of (Histocompatibility Minor 13), a signal peptide peptidase involved in epitope generation. LOI samples featured overexpression, both compared to normal solid tissues ( = 3.00 × 10 ) and non-LOI ( = 1.27 × 10 ) samples. Upon adjustment for age and sex, expression was significantly associated with poor survival ( = 7.10 × 10 ). Moreover, overexpression consistently exacerbated with increasing tumor stage ( = 2.90 × 10 ). For , LOI was observed in normal solid tissues, but the prevalence did not increase in cancer. In conclusion, LOI is an early event in ccRCC, causing overexpression leading to poor prognosis.