Relative Copy Number Gain of MYC in Diagnostic Needle Biopsies is an Independent Prognostic Factor for Prostate Cancer Patients

Ribeiro, Franclim R.; Henrique, Rui; Martins, Ana Teresa; Jerónimo, Carmen; Teixeira, Manuel R.

doi:10.1016/j.eururo.2006.09.018

Cited by 48 publications

(42 citation statements)

References 27 publications

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“…The prognostic significance of 8q gain was further confirmed by fluorescence in situ hybridization in an independent series of paraffin-embedded biopsies with longer follow-up (23). When cytogenetic and epigenetic results were combined in the survival analysis, the presence of 8q gain or APC hypermethylation was associated with disease progression.…”

Section: Discussionmentioning

confidence: 78%

High Promoter Methylation Levels of APC Predict Poor Prognosis in Sextant Biopsies from Prostate Cancer Patients

Henrique

Ribeiro²,

Fonseca

et al. 2007

Clinical Cancer Research

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117

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Purpose: Prostate cancer is a highly prevalent malignancy and constitutes a major cause of cancer-related morbidity and mortality. Owing to the limitations of current clinical, serologic, and pathologic parameters in predicting disease progression, we sought to investigate the prognostic value of promoter methylation of a small panel of genes by quantitative methylation-specific PCR (QMSP) in prostate biopsies. Experimental Design: Promoter methylation levels of APC, CCND2, GSTP1, RARB2, and RASSF1A were determined by QMSP in a prospective series of 83 prostate cancer patients submitted to sextant biopsy. Clinicopathologic data [age, serum prostate-specific antigen (PSA), stage, and Gleason score] and time to progression and/or death from prostate cancer were correlated with methylation findings. Log-rank test and Cox regression model were used to identify which epigenetic markers were independent predictors of prognosis. Results: At a median follow-up time of 45 months, 15 (18%) patients died from prostate cancer, and 37 (45%) patients had recurrent disease. In univariate analysis, stage and hypermethylation of APC were significantly associated with worse disease^specific survival, whereas stage, Gleason score, high diagnostic serum PSA levels, and hypermethylation of APC, GSTP1, and RASSF1A were significantly associated with poor disease-free survival. However, in the final multivariate analysis, only clinical stage and high methylation of APC were significantly and independently associated with unfavorable prognosis, i.e., decreased disease-free and diseasespecific survival. Conclusions: High-level APC promoter methylation is an independent predictor of poor prognosis in prostate biopsy samples and might provide relevant prognostic information for patient management.Prostate cancer (PCa) is a highly prevalent malignancy and constitutes a major cause of cancer-related morbidity and mortality, accounting for 33% of all cancers diagnosed and for nearly 10% of all cancer deaths in U.S. males (1). Although serum prostate-specific antigen (PSA) is generally recommended for PCa screening, confirmation of diagnosis requires a prostate biopsy (2). The relevance of this biopsy exceeds its diagnostic purposes because the assessment of tumor grade and extent has a substantial impact on therapeutic decision making. However, the information provided by prostate biopsy meets with important limitations owing to intra-and interobserver variability in Gleason grading and sampling error (3, 4). Moreover, other accepted prognostic factors (e.g., clinical stage and pretherapeutic serum PSA levels) that influence treatment decisions are rather imperfect in predicting disease progression. The ability to predict disease-specific and disease-free survival at diagnosis is Imaging, Diagnosis, Prognosis

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Section: Discussionmentioning

confidence: 78%

High Promoter Methylation Levels of APC Predict Poor Prognosis in Sextant Biopsies from Prostate Cancer Patients

Henrique

Ribeiro²,

Fonseca

et al. 2007

Clinical Cancer Research

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117

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“…The c-MYC gene, a well-known regulator of cell proliferation and programmed cell death, maps to this region and is overrepresented in prostate carcinoma with metastases (12). Moreover, the frequency of overrepresentation of the 8q24 locus in fluorescence in situ hybridization studies increases from prostate intraepithelial neoplasia to invasive primary carcinoma (13) and was associated with poor survival (14). However, no association between SNPs in the MYC gene (263 kb from rs1447295 in the telomeric direction) and prostate cancer risk was observed in our population (9).…”

Section: Discussionmentioning

confidence: 99%

Effect of Genetic Variability within 8q24 on Aggressiveness Patterns at Diagnosis and Familial Status of Prostate Cancer

Cussenot

Azzouzi

Bantsimba-Malanda

et al. 2008

Clinical Cancer Research

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Purpose: Recently, two independent loci located at 8q24 that contribute to prostate cancer risk in men of European origin were identified. Experimental Design: Using Bayesian probability network and logistic regression model, we searched for associations between 34 single-nucleotide polymorphisms (SNP) located at 8q24 and the aggressiveness patterns of prostate adenocarcinoma or familial history of cancers in 823 White Caucasian French men. Results: Probability network according to the Markov chain algorithm separated the SNPs into two main groups: The first one was linked to the locus marked by rs6983267 and the second one was linked to the locus marked by rs1447295. When the patients were stratified according to tumor stage and prostate-specific antigen value, the association between the variant genotypes from six SNPs located in the second network and prostate cancer risk was strongest or confined to the patients from the more aggressive classes. However, the association between prostate cancer risk and the CC genotype of rs7841264, which marked the recombination hotspot at 8q24, was confined to patients with the highest Gleason score (odds ratio, 2.15; 95% confidence interval, 1.27-3.64; P = 0.004). Interestingly, the G allele of rs6983267 was associated with familial prostate cancer risk. Conclusions: Our data further support that variability at 8q24 is associated with a high risk of aggressive prostate cancer at diagnosis and is linked with familial history of prostate cancer.These results corroborate that 8q24 SNPs must be evaluated in terms of prostate cancer aggressiveness markers to optimize early diagnosis procedures and management of the disease.

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“…Other candidates include c-MYC and EZH2. Amplification of the c-MYC oncogene has been shown to occur in PIN lesions as well as later stages of prostate cancer development (Ribeiro et al 2007, Shen & Abate-Shen 2010. Although in prostate cancer there is no genome-wide characterization of the interplay between AR and c-MYC, c-MYC physically interacts with AR (Gao et al 2013) and AR and c-MYC share some coregulators (see review Mills (2014)) including bromodomain-containing proteins, which bind to active chromatin via recognition of acetylated lysine on histones (Jang et al 2005).…”

Section: Ar In Prostate Cancer Initiationmentioning

confidence: 99%

Androgens and androgen receptor signaling in prostate tumorigenesis

Zhou¹,

Bolton²,

Jones³

2014

Journal of Molecular Endocrinology

165

112

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Androgens and androgen receptor (AR) signaling are necessary for prostate development and homeostasis. AR signaling also drives the growth of nearly all prostate cancer cells. The role of androgens and AR signaling has been well characterized in metastatic prostate cancer, where it has been shown that prostate cancer cells are exquisitely adept at maintaining functional AR signaling to drive cancer growth. As androgens and AR signaling are so intimately involved in prostate development and the proliferation of advanced prostate cancer, it stands to reason that androgens and AR are also involved in prostate cancer initiation and the early stages of cancer growth, yet little is known of this process. In this review, we summarize the current state of knowledge concerning the role of androgens and AR signaling in prostate tissue, from development to metastatic, castration-resistant prostate cancer, and use that information to suggest potential roles for androgens and AR in prostate cancer initiation.

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Relative Copy Number Gain of MYC in Diagnostic Needle Biopsies is an Independent Prognostic Factor for Prostate Cancer Patients

Cited by 48 publications

References 27 publications

High Promoter Methylation Levels of APC Predict Poor Prognosis in Sextant Biopsies from Prostate Cancer Patients

High Promoter Methylation Levels of APC Predict Poor Prognosis in Sextant Biopsies from Prostate Cancer Patients

Effect of Genetic Variability within 8q24 on Aggressiveness Patterns at Diagnosis and Familial Status of Prostate Cancer

Androgens and androgen receptor signaling in prostate tumorigenesis

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