Aberrant methylation of p16, HIC1, N33, and GSTP1 in tumor epithelium and tumor-associated cells in prostate cancer

Кекеева, Т. В.; Попова, О. П.; Shegai, P. V.; Alekseev, B. Ya.; Andreeva, Yu Yu; Zaletaev, D. V.; Немцова, М. В.

doi:10.1134/s0026893307010104

Cited by 14 publications

(14 citation statements)

References 21 publications

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“…In fact, relatively little work has been done to evaluate methylation in supporting tissues adjacent to any cancers, even though the importance of such tissues in cancer initiation and progression is increasingly well documented. Previous studies have evaluated methylation in stromal tissues adjacent to prostate cancer and have found gene methylation in tumor-associated stromal cells [18, 19]. The current study provides additional evidence for the potential importance of such stromal-epithelial interactions, and identifies subepithelial lymphocytic aggregates as a stromal component that may be particularly important in this interaction.…”

Section: Discussionsupporting

confidence: 55%

COX-2 (PTGS2) gene methylation in epithelial, subepithelial lymphocyte and stromal tissue compartments in a spectrum of esophageal squamous neoplasia

Dawsey

Roth

Adams

et al. 2008

Cancer Detection and Prevention

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Background-Previous studies have shown important effects of stromal elements in carcinogenesis. To explore the tumor-stromal relationship in esophageal neoplasia, we examined methylation of COX-2 (PTGS2), a gene etiologically associated with the development of gastrointestinal cancers, in adjacent foci of epithelium, subepithelial lymphocytes and nonlymphocytic stromal cells found in sections of normal squamous epithelium, squamous dysplasia and invasive esophageal squamous cell carcinoma.Methods-Adjacent foci of epithelium, subepithelial lymphocytic aggregates and non-lymphocytic stromal tissues were laser microdissected from six fully embedded, ethanol fixed, esophagectomy samples from Shanxi, China, a high-risk region for esophageal cancer. Promoter CpG site-specific hypermethylation status of COX-2 was determined using real-time methylation specific PCR (qMS-PCR) based on Taqman Chemistry. The methylation status of a subset of samples was confirmed by pyrosequencing.Results-Forty-nine microdissected foci were analyzed. COX-2 gene methylation was significantly more common in subepithelial lymphocytes (12/16 (75% of all foci)) than in epithelial foci (3/16 (19%)) or foci of non-lymphocytic stromal tissues (3/17 (18%)) (Fisher's Exact p=0.05). Two of three epithelial samples and all three stromal samples that showed COX-2 methylation were adjacent to foci of methylated subepithelial lymphocytes. Pyrosequencing confirmed the methylation status in a subset of samples.Corresponding authors/reprint requests: Mark J. Roth, MD, Nutritional Epidemiology Branch, DCEG, National Cancer Institute, 6120 Executive Boulevard, Suite 320, MSC 7232, Bethesda, Maryland 20892-7232, USA, +1-301-402-8276T, +1-301-496-6829F, mr166i@nih.gov. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Conflict of interestNone. Conclusions-In these esopohageal cancer patients, COX-2 gene methylation was more common in subepithelial lymphocytes than in adjacent epithelial or stromal cells in both grades of dysplasia and in foci of invasive cancer. These findings raise the possibility that methylation of subepithelial lymphocytes may be important for tumorigenesis. Future studies of gene methylation should consider separate evaluation of epithelial and non-epithelial cell populations. NIH Public AccessCondensed abstract-COX2 (PTGS2) gene methylation increases with disease severity and is more common in subepithelial lymphocytes than in adjacent epithelial or stromal cells in dysplastic and early invasive esophageal squamous cell cancer foci.

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Section: Discussionsupporting

confidence: 55%

COX-2 (PTGS2) gene methylation in epithelial, subepithelial lymphocyte and stromal tissue compartments in a spectrum of esophageal squamous neoplasia

Dawsey

Roth

Adams

et al. 2008

Cancer Detection and Prevention

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“…In prostate cancer, promoter hypermethylation of cyclin-dependent kinase inhibitor 2A, hypermethylated in cancer 1 protein, tumor suppressor candidate 3 and glutathione S-transferase P1 (GSTP1) is extremely abundant in cancer epithelial cells and CAFs (116). The GSTP1 promoter is methylated in >90% of prostate cancers.…”

Section: Epigenetic Alterationsmentioning

confidence: 99%

Genetic alterations and epigenetic alterations of cancer-associated fibroblasts

Che

2016

Oncology Letters

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Cancer-associated fibroblasts (CAFs) are one major type of component identified in the tumor microenvironment. Studies have focused on the genetic and epigenetic status of CAFs, since they are critical in tumor progression and differ phenotypically and functionally from normal fibroblasts. The present review summarizes the recent achievements in understanding the gene profiles of CAFs and pays special attention to their possible epigenetic alterations. A total of 7 possible genetic alterations and epigenetic changes in CAFs are discussed, including gene differential expression, karyotype analysis, gene copy number variation, loss of heterozygosis, allelic imbalance, microsatellite instability, post-transcriptional control and DNA methylation. These genetic and epigenetic characteristics are hypothesized to provide a deep understanding of CAFs and a perspective on their clinical significance.

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“…40–45 Furthermore, expression of these genes and their promoter methylation may correlate with the tumorigenesis, progression, and clinicopathological features of prostate cancer. 46–55 Many studies observed relatively high frequencies of promoter methylation in these genes: CD44 (32% to 78%), 39,41,46,56 cyclin D2 (32% to 99%), 42,43 LPL (38%), 49 EDNRB (49% to 100%), 19,39,57–59 HIC1, (89% to 100%), 18,19,60 PITX2, 52,54 and PTGS2 (65% to 88%). 19,45,55,59 The frequencies of methylation of these genes, with the exception of EDNRB and HIC1, were significantly higher in prostate tumors than in normal tissues.…”

Section: Hypermethylated Genes In Prostate Tumormentioning

confidence: 99%

“…However, the methylation status of EDNRB and HIC1 in prostate tumors parallels the respective normal tissue, although a high proportion of tumors are methylated. 18,19,39,58–60 Therefore, DNA methylation sites in EDNRB and HIC1 are not good candidates for a marker for prognostic marker for prostate cancer progression and an intervention target for prostate cancer.…”

Section: Hypermethylated Genes In Prostate Tumormentioning

confidence: 99%

Promoter Hypermethylation in Prostate Cancer

Park

2010

Cancer Control

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Background The prostate gland is the most common site of cancer and the second leading cause of cancer mortality in American men. It is well known that epigenetic alterations such as DNA methylation within the regulatory (promoter) regions of genes are associated with transcriptional silencing in cancer. Promoter hypermethylation of critical pathway genes could be potential biomarkers and therapeutic targets for prostate cancer. Methods This review discusses current information on methylated genes associated with prostate cancer development and progression. Results Over 30 genes have been investigated for promoter methylation in prostate cancer. These methylated genes are involved in critical pathways, such as DNA repair, metabolism, and invasion/metastasis. The role of hypermethylated genes in regulation of critical pathways in prostate cancer is reviewed. Conclusions These findings may provide new information of the pathogenesis of prostate cancer. Certain epigenetic alterations in prostate tumors are being translated into clinical practice for therapeutic use.

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Aberrant methylation of p16, HIC1, N33, and GSTP1 in tumor epithelium and tumor-associated cells in prostate cancer

Cited by 14 publications

References 21 publications

COX-2 (PTGS2) gene methylation in epithelial, subepithelial lymphocyte and stromal tissue compartments in a spectrum of esophageal squamous neoplasia

COX-2 (PTGS2) gene methylation in epithelial, subepithelial lymphocyte and stromal tissue compartments in a spectrum of esophageal squamous neoplasia

Genetic alterations and epigenetic alterations of cancer-associated fibroblasts

Promoter Hypermethylation in Prostate Cancer

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