Discovery and Validation of 3 Novel DNA Methylation Markers of Prostate Cancer Prognosis

Cottrell, Susan; Jung, Klaus; Kristiansen, Glen; Eltze, Elke; Semjonow, Axel; Ittmann, Michael; Hartmann, Arndt; Stamey, Thomas A.; Haefliger, Carolina; Weiß, Günter

doi:10.1016/j.juro.2007.01.010

Cited by 81 publications

(61 citation statements)

References 16 publications

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“…Patient clinical characteristics and methods used to isolate DNA have been reported (12). With a median of 60.2 months follow up, 14 patients had biochemical evidence of recurrent disease, whereas 22 did not.…”

Section: Clinical Profile Of Casesmentioning

confidence: 99%

Common Structural and Epigenetic Changes in the Genome of Castration-Resistant Prostate Cancer

et al. 2012

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Progression of primary prostate cancer to castration-resistant prostate cancer (CRPC) is associated with numerous genetic and epigenetic alterations that are thought to promote survival at metastatic sites. In this study, we investigated gene copy number and CpG methylation status in CRPC to gain insight into specific pathophysiologic pathways that are active in this advanced form of prostate cancer. Our analysis defined and validated 495 genes exhibiting significant differences in CRPC in gene copy number, including gains in androgen receptor (AR) and losses of PTEN and retinoblastoma 1 (RB1). Significant copy number differences existed between tumors with or without AR gene amplification, including a common loss of AR repressors in AR-unamplified tumors. Simultaneous gene methylation and allelic deletion occurred frequently in RB1 and HSD17B2, the latter of which is involved in testosterone metabolism. Lastly, genomic DNA from most CRPC was hypermethylated compared with benign prostate tissue. Our findings establish a comprehensive methylation signature that couples epigenomic and structural analyses, thereby offering insights into the genomic alterations in CRPC that are associated with a circumvention of hormonal therapy. Genes identified in this integrated genomic study point to new drug targets in CRPC, an incurable disease state which remains the chief therapeutic challenge. Cancer Res; 72(3); 616–25. ©2011 AACR.

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Section: Clinical Profile Of Casesmentioning

confidence: 99%

Common Structural and Epigenetic Changes in the Genome of Castration-Resistant Prostate Cancer

et al. 2012

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“…For example, ABHD9 is hypermethylated in human malignant melanomas [59], gastric cancers [60], adenoid cystic carcinomas of salivary glands [61], and colorectal carcinomas [62]. Hypermethylation of ABHD9 has been associated with prostate cancer recurrence [63, 64], and AHBD9 expression is also deregulated in some B cell malignancies [65]. Based on these studies, it is possible that ABHD9 substrates may contribute to cancer development.…”

Section: Introductionmentioning

confidence: 99%

Mammalian alpha beta hydrolase domain (ABHD) proteins: Lipid metabolizing enzymes at the interface of cell signaling and energy metabolism

Lord

Thomas

Brown

2013

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

136

145

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Dysregulation of lipid metabolism underlies many chronic diseases such as obesity, diabetes, cardiovascular disease, and cancer. Therefore, understanding enzymatic mechanisms controlling lipid synthesis and degradation is imperative for successful drug discovery for these human diseases. Genes encoding α/β hydrolase fold domain (ABHD) proteins are present in virtually all reported genomes, and conserved structural motifs shared by these proteins predict common roles in lipid synthesis and degradation. However, the physiological substrates and products for these lipid metabolizing enzymes and their broader role in metabolic pathways remain largely uncharacterized. Recently, mutations in several members of the ABHD protein family have been implicated in inherited inborn errors of lipid metabolism. Furthermore, studies in cell and animal models have revealed important roles for ABHD proteins in lipid metabolism, lipid signal transduction, and metabolic disease. The purpose of this review is to provide a comprehensive summary surrounding the current state of knowledge regarding mammalian ABHD protein family members. In particular, we will discuss how ABHD proteins are ideally suited to act at the interface of lipid metabolism and signal transduction. Although, the current state of knowledge regarding mammalian ABHD proteins is still in its infancy, this review highlights the potential for the ABHD enzymes as being attractive targets for novel therapies targeting metabolic disease.

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“…In a methylation oligonucleotide microarray study of 304 frozen prostatectomy samples, Cottrell et al previously reported that promoter region methylation of ABHD9 was significantly increased in patients who experienced early PSA recurrence versus non-recurrent men (Bonferroni-adjusted P < 0.05) (10). The significance of the result with respect to biochemical recurrence was then confirmed in a cohort of 605 RP patients (12).…”

Section: Discussionmentioning

confidence: 99%

Validation Study of Genes with Hypermethylated Promoter Regions Associated with Prostate Cancer Recurrence

Stott-Miller

Zhao

Wright

et al. 2014

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background One challenge in prostate cancer (PCa) is distinguishing indolent from aggressive disease at diagnosis. DNA promoter hypermethylation is a frequent epigenetic event in PCa, but few studies of DNA methylation in relation to features of more aggressive tumors or PCa recurrence have been completed. Methods We used the Infinium® HumanMethylation450 BeadChip to assess DNA methylation in tumor tissue from 407 patients with clinically localized PCa who underwent radical prostatectomy. Recurrence status was determined by follow-up patient surveys, medical record review, and linkage with the SEER registry. The methylation status of 14 genes for which promoter hypermethylation was previously correlated with advanced disease or biochemical recurrence was evaluated. Average methylation level for promoter region CpGs in patients who recurred compared to those with no evidence of recurrence was analyzed. For two genes with differential methylation, time to recurrence was examined. Results During an average follow-up of 11.7 years, 104 (26%) patients recurred. Significant promoter hypermethylation in at least 50% of CpG sites in two genes, ABHD9 and HOXD3, was found in tumors from patients who recurred compared to those without recurrence. Evidence was strongest for HOXD3 (lowest P = 9.46x10−6), with higher average methylation across promoter region CpGs associated with reduced recurrence-free survival (P = 2×10−4). DNA methylation profiles did not differ by recurrence status for the other genes. Conclusions These results validate the association between promoter hypermethylation of ADHB9 and HOXD3 and PCa recurrence. Impact Tumor DNA methylation profiling may help distinguish PCa patients at higher risk for disease recurrence.

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Discovery and Validation of 3 Novel DNA Methylation Markers of Prostate Cancer Prognosis

Cited by 81 publications

References 16 publications

Common Structural and Epigenetic Changes in the Genome of Castration-Resistant Prostate Cancer

Common Structural and Epigenetic Changes in the Genome of Castration-Resistant Prostate Cancer

Mammalian alpha beta hydrolase domain (ABHD) proteins: Lipid metabolizing enzymes at the interface of cell signaling and energy metabolism

Validation Study of Genes with Hypermethylated Promoter Regions Associated with Prostate Cancer Recurrence

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