Reprint of: The prostate cancer genome: Perspectives and potential

Barbieri, Christopher E.; Tomlins, Scott A.

doi:10.1016/j.urolonc.2015.01.002

Cited by 7 publications

(4 citation statements)

References 65 publications

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“…Under normal conditions, MDM2 inhibits the transcriptional activity of p53 and regulates cell cycle, DNA repair, senescence, apoptosis and angiogenesis (Pant and Lozano, 2014). The perturbation of these processes allows mutations to accumulate in a cell, which can be transferred to future generations, thereby increasing the risk of developing cancer (Barbieri and Tomlins, 2015).…”

Section: Introductionmentioning

confidence: 99%

Alterations in PTEN, MDM2, TP53 and AR protein and gene expression are associated with canine prostate carcinogenesis

Calderón

Fonseca-Alves

Kobayashi

et al. 2016

Research in Veterinary Science

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The PTEN, AR, MDM2 and p53 protein network plays a central role in the development of many human cancers, thus eliciting the development of targeted cancer therapeutics. Dogs spontaneously develop tumours, and they are considered a good model for comparative oncology initiatives. Due to the limited information on these proteins in canine tumours, this study aimed to investigate gene and protein alterations in PTEN, AR, MDM2 and p53 in canine prostate cancer (PC). Protein expression was evaluated by immunohistochemistry (15 normal, 22 proliferative inflammatory atrophy (PIA) and 19 PC samples) and Western blotting (2 normal prostate tissue, 2 BPH, 2 PIA samples and 2 PC samples) and gene expression by RT-qPCR (10 normal, 10 PIA and 15 PC samples) of formalin-fixed tissue. We identified nuclear and cytoplasmic expression of PTEN and p53 in all samples, with only nuclear staining found for MDM2 and AR. Our results revealed high expression of MDM2 in PC and PIA samples compared to normal samples, whereas PTEN, P53 and AR expression was down-regulated in PC compared to normal tissue. All tumour samples (n=19) showed loss of nuclear PTEN expression, and all cancer mimickers showed positive nuclear staining. Therefore, nuclear PTEN staining could be a good diagnostic marker for differentiating between malignant lesions and mimickers. Canine prostate carcinogenesis involves increased expression of MDM2 in association with decreased expression of PTEN, p53 and AR, such as occurs in hormone refractory PC in men. Thus, dogs may be an important model for studying advanced stage PC.

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Section: Introductionmentioning

confidence: 99%

Alterations in PTEN, MDM2, TP53 and AR protein and gene expression are associated with canine prostate carcinogenesis

Calderón

Fonseca-Alves

Kobayashi

et al. 2016

Research in Veterinary Science

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“…Changes in epigenetic modifications may result in inaccurate activation or inhibition of signaling pathways leading to the development of cancer [11]. It is well established that PCa has a low number of somatic gene mutations [19]. Consequently, epigenetic alterations are considered hallmarks for PCa development and progression [20,21].…”

Section: Discussionmentioning

confidence: 99%

5hmC Level Predicts Biochemical Failure Following Radical Prostatectomy in Prostate Cancer Patients with ERG Negative Tumors

Kristensen

Strand

Røder

et al. 2019

IJMS

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This study aimed to validate whether 5-hydroxymethylcytosine (5hmC) level in combination with ERG expression is a predictive biomarker for biochemical failure (BF) in men undergoing radical prostatectomy (RP) for prostate cancer (PCa). The study included 592 PCa patients from two consecutive Danish RP cohorts. 5hmC level and ERG expression were analyzed using immunohistochemistry in RP specimens. 5hmC was scored as low or high and ERG was scored as negative or positive. Risk of BF was analyzed using stratified cumulative incidences and multiple cause-specific Cox regression using competing risk assessment. Median follow-up was 10 years (95% CI: 9.5–10.2). In total, 246 patients (41.6%) had low and 346 patients (58.4%) had high 5hmC level. No significant association was found between 5hmC level or ERG expression and time to BF (p = 0.2 and p = 1.0, respectively). However, for men with ERG negative tumors, high 5hmC level was associated with increased risk of BF following RP (p = 0.01). In multiple cause-specific Cox regression analyses of ERG negative patients, high 5hmC expression was associated with time to BF (HR: 1.8; 95% CI: 1.2–2.7; p = 0.003). In conclusion, high 5hmC level was correlated with time to BF in men with ERG negative PCa, which is in accordance with previous results.

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“…However, only a small number of such alterations have been causally linked to cancer and they vary from tumor to tumor [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

A Novel Method for Mutation Analysis Using Genomic DNA Obtained from Immunohistochemistry-Stained Sections

Patel¹

2015

J Mol Biomark Diagn

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Background: Tumor biopsies obtained from patients are often limited in size and availability, and the ability to perform multiple diagnostic assays depends on the quantity and quality of the tissue. Here we describe and evaluate a method for performing DNA-based mutational analyses after immunohistochemistry analysis has been performed, using a single tissue section.Method: Immunohistochemistry analysis was performed on 4-5 µm formalin-fixed paraffin-embedded tumor tissue sections and immunohistochemistry-stained sections were stored for subsequent genomic analysis. DNA was isolated from these immunohistochemistry-stained sections and DNA quality was assessed using a multiplexpolymerase chain reaction method as well as real time quantitative polymerase chain reaction of commonly used reference genes. Subsequently, genomic DNA was pre-amplified and mutations in KRAS, BRAF, NRAS and PIK3CA were detected by validated Taqman assays. Comparisons were made with results from unstained formalinfixed paraffin-embedded sections obtained from the same paraffin block. Results:Our results demonstrate that genomic DNA isolated from immunohistochemistry-stained and unstained formalin-fixed paraffin-embedded tissue sections are comparable in quality and are suitable for down-stream analysis using polymerase chain reaction based assays. We also found that the sensitivity and specificity in detecting hotspot mutations are comparable in both sources of genomic DNA. This study reports 100% concordance in detecting hotspot mutations in KRAS, BRAF, NRAS and PIK3CA using quantitative real-time polymerase chain reaction between stained and unstained formalin-fixed paraffin-embedded sections. Conclusion:We conclude that by using our novel approach, it is possible to perform immunohistochemistry staining followed by genomic analysis using a single 4-5 µm section of formalin-fixed paraffin-embedded tissue.

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Reprint of: The prostate cancer genome: Perspectives and potential

Cited by 7 publications

References 65 publications

Alterations in PTEN, MDM2, TP53 and AR protein and gene expression are associated with canine prostate carcinogenesis

Alterations in PTEN, MDM2, TP53 and AR protein and gene expression are associated with canine prostate carcinogenesis

5hmC Level Predicts Biochemical Failure Following Radical Prostatectomy in Prostate Cancer Patients with ERG Negative Tumors

A Novel Method for Mutation Analysis Using Genomic DNA Obtained from Immunohistochemistry-Stained Sections

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