The tumor suppressor gene NKX3.1 and the LPL gene are located in close proximity on chromosome 8, and their deletion has been reported in multiple studies. However, the significance of LPL loss may be misinterpreted due to its co-deletion with NKX3.1, a well-established event in prostate carcinogenesis. This study investigates whether LPL deletion represents a biologically relevant event or occurs merely as a bystander to NKX3.1 loss. We analyzed 28 formalin-fixed paraffin-embedded prostate cancer samples with confirmed LPL 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 NKX3.1 and LPL in 54 patients. Notably, NKX3.1 loss without accompanying LPL deletion was observed in eight additional cases. These findings suggest that LPL deletion is a passenger event secondary to NKX3.1 loss and underscore the importance of cautious interpretation of cytogenetic findings involving the LPL locus.

Department of Applied Mathematics Faculty of Electrical Engineering and Computer Science VSB Technical University of Ostrava 708 00 Ostrava Czech Republic

Department of Biomedical Engineering Faculty of Electrical Engineering and Communication Brno University of Technology 616 00 Brno Czech Republic

Department of Clinical and Molecular Pathology Institute of Molecular and Translational Medicine Palacky University and University Hospital Olomouc 779 00 Olomouc Czech Republic

Department of Deputy Director for Science Research and Education University Hospital Ostrava 703 00 Ostrava Czech Republic

Department of Urology University Hospital Ostrava 703 52 Ostrava Czech Republic

EUC Laboratories CGB a s 703 00 Ostrava Czech Republic

Institute of Clinical and Molecular Pathology and Medical Genetics University Hospital Ostrava and Medical Faculty Ostrava 703 52 Ostrava Czech Republic

Molecular Systems Biology Department of Functional and Evolutionary Ecology Faculty of Life Sciences University of Vienna 1030 Vienna Austria

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