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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 <i>IGF2</i>, 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. <i>p</i> = 2.74 × 10⁻³) of <i>HM13</i> (Histocompatibility Minor 13), a signal peptide peptidase involved in epitope generation. <i>HM13</i> LOI samples featured <i>HM13</i> overexpression, both compared to normal solid tissues (<i>p</i> = 3.00 × 10⁻⁷) and non-LOI (<i>p</i> = 1.27 × 10⁻²) samples. Upon adjustment for age and sex, <i>HM13</i> expression was significantly associated with poor survival (<i>p</i> = 7.10 × 10⁻⁵). Moreover, <i>HM13</i> overexpression consistently exacerbated with increasing tumor stage (<i>p</i> = 2.90 × 10⁻⁸). For <i>IGF2</i>, LOI was observed in normal solid tissues, but the prevalence did not increase in cancer. In conclusion, <i>HM13</i> LOI is an early event in ccRCC, causing overexpression leading to poor prognosis.