Progressive Spreading of DNA Methylation in the GSTP1 Promoter CpG Island across Transitions from Precursors to Invasive Prostate Cancer.

Autor:	Gupta H; Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland., Inoue H; Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland.; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.; Department of Urology, Ikeda Municipal Hospital, Osaka, Japan., Nakai Y; Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland.; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.; Department of Urology, Osaka International Cancer Institute, Osaka, Japan., Nakayama M; Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland.; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.; Department of Urology, Osaka International Cancer Institute, Osaka, Japan., Jones T; Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland.; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland., Hicks JL; Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland.; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland., Kumar B; Independent Computer Scientist, Monte Sereno, California., Gurel M; Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland.; BenevolentAI, London, United Kingdom.; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland., Nelson WG; Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland.; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland., De Marzo AM; Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland.; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland., Yegnasubramanian S; Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland.; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Jazyk:	angličtina
Zdroj:	Cancer prevention research (Philadelphia, Pa.) [Cancer Prev Res (Phila)] 2023 Aug 01; Vol. 16 (8), pp. 449-460.
DOI:	10.1158/1940-6207.CAPR-22-0485
Abstrakt:	Glutathione S-transferase pi 1 (GSTP1) is lowly expressed in normal prostate luminal cells and becomes induced in most proliferative inflammatory atrophy (PIA) lesions. GSTP1 becomes silenced in prostatic intraepithelial neoplasia (PIN) and prostate adenocarcinoma (CaP) via cytosine-phospho-guanine (CpG) island promoter hypermethylation. However, GSTP1 methylation patterns in PIA and PIN, and their relationship to patterns in CaP are poorly understood. We used bisulfite genomic sequencing to examine patterns of GSTP1 promoter CpG island methylation in laser capture microdissected benign, PIA, PIN, and CaP regions from 32 subjects that underwent radical prostatectomy. We analyzed 908 sequence clones across 24 normal epithelium, 37 PIA, 18 PIN, and 23 CaP regions, allowing assessment of 34,863 CpG sites with allelic phasing. Normal and PIA lesions were mostly unmethylated with 0.52 and 1.3% of total CpG sites methylated, respectively. PIN and CaP lesions had greater methylation with 24% and 51% of total CpG sites methylated, respectively. The degree of GSTP1 methylation showed progression from PIA << PIN < CaP. PIN lesions showed more partial methylation compared with CaP lesions. Partially methylated lesions were enriched for methylation changes at AP1 and SP1 transcription factor binding sites. These results demonstrate that methylation density in the GSTP1 CpG island in PIN was intermediate relative to that in normal prostate epithelium/PIA and CaP lesions. These results are consistent with gradual spreading of DNA methylation centered at the SP1/AP1 transcription factor binding sites in precursor lesions, with subsequent spreading of methylation across the entire CpG island in transition to CaP. Prevention Relevance: DNA hypermethylation at the GSTP1 promoter progressively spreads from being unmethylated in normal prostate to intermediate levels in precursor lesions to extensive methylation in cancer. This molecular progression of GSTP1 promoter methylation patterns in early prostate carcinogenesis could be useful for identification and interception of prostate cancer precursors. (©2023 American Association for Cancer Research.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu