Seung-Hyun Junga, b, †, Sun Shina, b, †, Min Sung Kimc, In-Pyo Baeka, b, Ji Youl Leed, Sung Hak Leee, Tae-Min Kimf, Sug Hyung Leec,*, Yeun-Jun Chunga, b, *
a Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, Korea
b Integrated Research Center for Genome Polymorphism, College of Medicine, The Catholic University of Korea, Seoul, Korea
c Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea
d Department of Urology, College of Medicine, The Catholic University of Korea, Seoul, Korea
e Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea
f Department of Medical Informatics, College of Medicine, The Catholic University of Korea, Seoul, Korea
†These two authors contributed equally to this work.
Although high grade prostatic intraepithelial neoplasia (HGPIN) is considered a neoplastic lesion that precedes prostate cancer (PCA), the genomic structures of HGPIN remain unknown.
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.
HGPIN genomes harbor relatively fewer mutations and CNAs than PCA but require additional hits for the progression.
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