Methylation changes in faecal DNA: a marker for colorectal cancer screening?

Müller, Hannes M.; Oberwalder, Michael; Fiegl, Heidi; Morandell, Maria; Goebel, Georg; Zitt, Matthias; Mühlthaler, Markus; Öfner, Dietmar; Margreiter, Raimund; Widschwendter, Martin

doi:10.1016/s0140-6736(04)16002-9

Cited by 258 publications

(191 citation statements)

References 5 publications

Supporting

Mentioning

183

Contrasting

Unclassified

Order By: Relevance

“…Recently, methylated SFRP2 was suggested as a marker candidate for colorectal cancer screening, as it was recovered in stool samples from a majority of patients with colorectal cancer. 39 In our study, SFRP1, 4 and 5 appeared to be more discriminant for Barrett's esophagus and esophageal adenocarcinoma and may be more suitable candidate markers for these lesions. Subsequent studies will need to be conducted to determine their sensitivity in detecting Barrett's esophagus by stool assay or other approaches (e.g., esophageal swabbing).…”

Section: Discussionsupporting

confidence: 56%

Aberrant methylation of secreted frizzled‐related protein genes in esophageal adenocarcinoma and Barrett's esophagus

Zou

Molina

Harrington

et al. 2005

Intl Journal of Cancer

135

View full text Add to dashboard Cite

Hypermethylation of secreted frizzled-related proteins (SFRP) genes frequently occurs with several cancers but has not been studied in esophageal adenocarcinoma or its precursor-Barrett's esophagus. To explore the role of SFRP methylation in the neoplastic progression of Barrett's esophagus and to evaluate methylated SFRP genes as biomarkers for Barrett's esophagus and cancer, methylation of SFRP genes was determined in esophageal adenocarcinomas, Barrett's esophagus and normal epithelia using methylation-specific PCR. Protein expression of SFRP genes was then assessed in these tissues by immunohistochemistry. The mRNA expression of SFRP genes was quantified by real-time reverse-transcription PCR in esophageal adenocarcinoma cell lines with and without demethylation by 5-aza-2 0 deoxycytidine and inhibition of deacetylation by trichostatin A treatment. Hypermethylation of SFRP1, 2, 4 and 5 was detected in 93%, 83%, 73% and 85% of 40 cancers; 81%, 89%, 78% and 73% of 37 Barrett's epithelia; 25%, 64%, 32% and 21% of 28 adjacent normal epithelia from Barrett's patients; and 10%, 67%, 0% and 13% of 30 normal esophagogastric epithelia from healthy individuals, respectively (p < 0.001 for SFRP1, 4 and 5; p < 0.05 for SFRP2). Protein expression of SFRP1, 2 and 4 was downregulated in 87%, 67% and 90% of cancers, and expression correlated inversely with grade and stage of cancers and with grade of dysplasia. Expression of SFRP2 and SFRP4 proteins was lower in cancers with corresponding gene methylation (p < 0.05). Demethylation treatment effectively re-expressed SFRP mRNA in cancer cell lines. Thus, hypermethylation of SFRP genes is a common early event in the evolution of esophageal adenocarcinoma, and methylation of SFRP1, 4 and 5 might serve as biomarkers for Barrett's neoplasia. Aberrant promoter methylation appears to functionally silence SFRP gene expression in esophageal adenocarcinoma. ' 2005 Wiley-Liss, Inc.Key words: DNA methylation; esophageal adenocarcinoma; Barrett's esophagus; secreted frizzed-related protein (SFRP); tumor markerThe incidence of esophageal adenocarcinoma is increasing at an alarming rate in western countries.1 Nearly all such cancers arise from Barrett's esophagus, a metaplastic condition in which intestinal-type epithelium replaces the normal squamous epithelium. 2The molecular mechanisms of this premalignant condition remain incompletely understood. Inactivation of tumor suppressor genes by promoter hypermethylation has been considered as a potentially important mechanism involved in the development of Barrett's esophagus.3 Several tumor suppressor genes, most notably p16, have been found to undergo epigenetic changes in Barrett's esophagus. [3][4][5][6] Aberrant promoter methylation of a new class of tumor suppressor genes, 7 secreted frizzled-related protein (SFRP) genes, has been described in colon and gastric cancers.8 SFRPs are secreted glycoproteins that work as inhibitive modulators of a putative tumorigenic pathway-the Wnt pathway, in which signals are transduced by Wnt ligands t...

show abstract

Section: Discussionsupporting

confidence: 56%

Aberrant methylation of secreted frizzled‐related protein genes in esophageal adenocarcinoma and Barrett's esophagus

Zou

Molina

Harrington

et al. 2005

Intl Journal of Cancer

135

View full text Add to dashboard Cite

show abstract

“…SFRP2 was the first reported DNA methylation marker in stool, has shown a sensitivity of 77%-90% and specificity of 77% [66] and has since been studied extensively. SFRP2 methylation has been shown to be the most sensitive biomarker for CRC, with detection rates ranging from 77% to 94% ( has been well documented that many miRNAs are regulated by the methylation of their promoter region, and some miRNAs target epigenetic activity.…”

Section: Dna Methylation Biomarkers In Stoolmentioning

confidence: 99%

Advances in epigenetic biomarker research in colorectal cancer

Kuang

2014

WJG

View full text Add to dashboard Cite

Colorectal cancer (CRC) causes approximately 600000 deaths annually and is the third leading cause of cancer mortality worldwide. Despite significant advancements in treatment options, CRC patient survival is still poor owing to a lack of effective tools for early diagnosis and a limited capacity for optimal therapeutic decision making. Since there exists a need to find new biomarkers to improve diagnosis of CRC, the research on epigenetic biomarkers for molecular diagnostics encourages the translation of this field from the bench to clinical practice. Epigenetic alterations are thought to hold great promise as tumor biomarkers. In this review, we will primarily focus on recent advances in the study of epigenetic biomarkers for colorectal cancer and discuss epigenetic biomarkers, including DNA methylation, microRNA expression and histone modification, in cancer tissue, stool, plasma, serum, cell lines and xenografts. These studies have improved the chances that epigenetic biomarkers will find a place in the clinical practices of screening, early diagnosis, prognosis, therapy choice and recurrence surveillance for CRC patients. However, these studies have typically been small in size, and evaluation at a larger scale of well-controlled randomized clinical trials is the next step that is necessary to increase the quality of epigenetic biomarkers and ensure their widespread clinical use.

show abstract

“…In fact, inactivation of RASSF2A is much earlier and more frequent in CRCs than inactivation of RASSF1A, which occurs at around 15-45% (Akino et al, 2005;Hesson et al, 2005). It has recently been shown that methylation in a subset of genes in CRCs and matching faecal tissue may form a basis for early detection (Muller et al, 2004). The recent data showing early, frequent and tumour-specific RASSF2A methylation in CRCs suggests it would be an ideal molecular biomarker for early detection of CRCs.…”

Section: Rassf1mentioning

confidence: 99%