Prognostic Significance of Biallelic Loss of PTEN in Clear Cell Renal Cell Carcinoma

Purpose: We investigated the clinical implications of biallelic loss of PTEN in clear cell renal cell carcinoma and whether PTEN biallelic loss would induce p53 dependent cellular senescence. Materials and Methods: Data were obtained using the CGDS-R package from the TCGA data set kirc_tcga_pub. PTEN allelic status was classified into 3 groups, including biallelic PTEN loss (homozygous deletion or combined heterozygous deletion and mutation), monoallelic PTEN loss (heterozygous deletion or mutation) and absent allelic loss. Univariate and multivariate overall survival analysis was performed. TP53 allelic loss and mean expression of genes related to p53 dependent cellular senescence were compared. Results: Of 416 patients with clear cell renal cell carcinoma 11 (2.6%) had biallelic PTEN loss and 69 (16.6%) had monoallelic loss. PTEN allelic loss was associated with late tumor stage and high histological grade. Patients with biallelic loss showed worse overall survival after adjusting for age and AJCC tumor stage (HR 3.1, 95% CI 1.4-6.8, p = 0.005). About half of the patients with PTEN biallelic loss had accompanying TP53 allelic loss. Biallelic loss of PTEN did not increase the expression of genes related to p53 dependent cellular senescence. Conclusions: PTEN biallelic loss may be a prognostic marker for clear cell renal cell carcinoma. It does not seem to induce p53 dependent cellular senescence, partly due to allelic loss of TP53.