Cells Comprising the Prostate Cancer Microenvironment Lack Recurrent Clonal Somatic Genomic Aberrations

Area of Science:

• Oncology
• Genomics
• Cancer Biology

Background:

• Prostate cancer-associated stroma (CAS) influences tumor progression and metastasis.
• Gene expression changes in CAS are significant, but the role of genomic alterations in benign cells of the tumor microenvironment (TME) is debated.

Purpose of the Study:

• To evaluate the nuclear and mitochondrial DNA integrity of prostate carcinoma cells and CAS.
• To determine if genomic alterations in the TME underlie observed gene expression changes and oncogenic phenotypes.

Main Methods:

• Whole-genome copy-number analyses (aCGH)
• Targeted sequencing of TP53
• Fluorescence in situ hybridization (FISH)
• Analysis of mitochondrial DNA (mtDNA)

Main Results:

• CAS exhibited a copy-neutral diploid genome with rare somatic copy-number aberrations (SCNA).
• Prostate carcinoma cells showed recurrent SCNAs (e.g., gains at 3q, 7p, 8q; losses at 8p, 10q).
• Few somatic mtDNA mutations were found in stroma compared to neoplastic epithelial cells.

Conclusions:

• Gene expression changes in prostate cancer-adjacent stroma are not driven by frequent genomic alterations in the TME.
• The stroma's contribution to prostate cancer development and progression is not explained by TME genomic instability.