Elsevier

European Urology

Volume 69, Issue 5, May 2016, Pages 823-830
European Urology

Platinum Priority – Prostate Cancer
Editorial by Michael C. Haffner and Christopher E. Barbieri on pp. 831–833 of this issue
Genetic Progression of High Grade Prostatic Intraepithelial Neoplasia to Prostate Cancer

https://doi.org/10.1016/j.eururo.2015.10.031Get rights and content
Under a Creative Commons license
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Abstract

Background

Although high grade prostatic intraepithelial neoplasia (HGPIN) is considered a neoplastic lesion that precedes prostate cancer (PCA), the genomic structures of HGPIN remain unknown.

Objective

Identification of the genomic landscape of HGPIN and the genomic differences between HGPIN and PCA that may drive the progression to PCA.

Design, settings, and participants

We analyzed 20 regions of paired HGPIN and PCA from six patients using whole-exome sequencing and array-comparative genomic hybridization.

Outcome measurements and statistical analysis

Somatic mutation and copy number alteration (CNA) profiles of paired HGPIN and PCA were measured and compared.

Results and limitations

The number of total mutations and CNAs of HGPINs were significantly fewer than those of PCAs. Mutations in FOXA1 and CNAs (1q and 8q gains) were detected in both HGPIN and PCA (‘common’), suggesting their roles in early PCA development. Mutations in SPOP, KDM6A, and KMT2D were ‘PCA-specific’, suggesting their roles in HGPIN progression to PCA. The 8p loss was either ‘common’ or ‘PCA-specific’. In-silico estimation of evolutionary ages predicted that HGPIN genomes were much younger than PCA genomes. Our data show that PCAs are direct descendants of HGPINs in most cases that require more genomic alterations to progress to PCA. The nature of heterogeneous HGPIN population that might attenuate genomic signals should further be studied.

Conclusions

HGPIN genomes harbor relatively fewer mutations and CNAs than PCA but require additional hits for the progression.

Patient summary

In this study, we suggest a systemic diagram from high grade prostatic intraepithelial neoplasia (HGPIN) to prostate cancer (PCA). Our results provide a clue to explain the long latency from HGPIN to PCA and provide useful information for the genetic diagnosis of HGPIN and PCA.

Keywords

Prostatic intraepithelial neoplasia
Prostate cancer genomes

Cited by (0)

These two authors contributed equally to this work.