Genomic Characterization of Prostatic Basal Cell Carcinoma

Area of Science:

• Urology
• Oncology
• Genomics

Background:

• Basal cell carcinoma (BCC) of the prostate is a rare entity, distinct from the common acinar adenocarcinoma (AAC).
• The molecular landscape and genomic alterations of prostatic BCC remain largely undescribed.
• Understanding these differences is crucial for elucidating BCC's unique biology and potential therapeutic targets.

Purpose of the Study:

• To comprehensively describe the molecular spectrum of prostatic basal cell carcinoma.
• To identify specific genomic alterations distinguishing BCC from AAC.
• To investigate the functional role of identified genetic changes in BCC pathogenesis.

Main Methods:

• Whole genome sequencing was performed on archival formalin-fixed, paraffin-embedded specimens from two cases of prostatic BCC.
• Analysis focused on copy number alterations and somatic mutations.
• In vitro experiments assessed the functional impact of CYLD protein depletion on prostatic basal cell proliferation.

Main Results:

• Prostatic BCCs exhibited a low overall copy number and mutational burden.
• A recurrent copy number loss of chromosome 16 was consistently observed across both cases.
• Putative driver gene alterations were identified in KIT, DENND3, PTPRU, MGA, and CYLD.

Conclusions:

• Prostatic BCC displays a distinct genomic profile compared to acinar adenocarcinoma.
• Loss of chromosome 16 may play a significant role in the pathogenesis of this rare prostate tumor.
• CYLD alterations suggest a potential mechanism involving altered prostatic basal cell proliferation.