What question did this study set out to answer?

The study aims to explore the genetic changes and clonal dynamics from normal prostate epithelium to prostate cancer via high-grade prostatic intraepithelial neoplasia.

April 5, 2026

Abstract 3532: Genetic insights into clonal evolution from normal prostate epithelium to cancer via HighGradePIN

Key Points

The study aims to explore the genetic changes and clonal dynamics from normal prostate epithelium to prostate cancer via high-grade prostatic intraepithelial neoplasia.
Performed laser-capture microdissection to obtain samples from normal prostate epithelium, HGPIN, and prostate cancer.
Conducted whole-exome sequencing on collected samples.
Utilized NanoSeq for accurate genome-wide mutation detection.
Identified over 10,000 single nucleotide variations (SNVs) and insertions/deletions (indels) in normal prostate epithelium samples.
Estimated a mutation accumulation rate of 0.205 mutations/year/exon in normal prostate epithelium.
Discovered shared mutations between normal epithelium, HGPIN, and prostate cancer, indicating a possible common clonal origin.

Abstract

Abstract Background Prostate cancer (PC) is one of the most prevalent cancers in the developed world, where its incidence is still increasing. Most PCs are thought to arise from high-grade prostatic intraepithelial neoplasia (HGPIN), a well-recognized precursor lesion. However, the genetic landscape of HGPIN and its relationship with normal prostate epithelium (NPE) and PC remains to be fully explored. To clarify the early genetic events and clonal dynamics underlying PC development, we performed comprehensive genomic profiling of NPE, HGPIN, and PC. Methods We performed laser-capture microdissection (LMD) to obtain samples from PC (n = 49), HGPIN (n = 77), and NEP (n =393), which were subjected to whole-exome sequencing (WES). We measured genome-wide mutation burdens in normal prostate epithelium from 5 patients using a highly accurate sequencing platform, Nanoseq. Results In NanoSeq, a total of 10,047 SNVs Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3532.

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