Deletions of LPL and NKX3.1 in Prostate Cancer Progression: Game Changers or By-Standers in Tumor Evolution

The tumor suppressor gene <i>NKX3</i>.1 and the <i>LPL</i> gene are located in close proximity on chromosome 8, and their deletion has been reported in multiple studies. However, the significance of <i>LPL</i> loss may be misinterpreted due to its co-deletion with <i>NKX3.1</i>, a well-established event in prostate carcinogenesis. This study investigates whether <i>LPL</i> deletion represents a biologically relevant event or occurs merely as a bystander to <i>NKX3.1</i> loss. We analyzed 28 formalin-fixed paraffin-embedded prostate cancer samples with confirmed <i>LPL</i> deletion and 28 without. Immunohistochemical staining was performed, and previously published whole-genome sequencing data from 103 prostate cancer patients were reanalyzed. Deletion of the 8p21.3 region was associated with higher Gleason grade groups. While NKX3.1 expression was significantly reduced in prostate cancer compared to benign prostatic hyperplasia, LPL protein expression showed no significant difference between cancerous and benign tissue, nor was it affected by the 8p21.3 deletion status. Copy number analysis confirmed the co-deletion of <i>NKX3.1</i> and <i>LPL</i> in 54 patients. Notably, <i>NKX3.1</i> loss without accompanying <i>LPL</i> deletion was observed in eight additional cases. These findings suggest that <i>LPL</i> deletion is a passenger event secondary to <i>NKX3.1</i> loss and underscore the importance of cautious interpretation of cytogenetic findings involving the <i>LPL</i> locus.