DNA Stool Test for Colorectal Cancer: Hypermethylation of the Secreted Frizzled-Related Protein-1 Gene

Zhang, Wei; Bauer, Michael; Croner, Roland S.; Pelz, Jörg; Lodygin, Dimitri; Hermeking, Heiko; Stürzl, Michael; Hohenberger, Werner; Matzel, Klaus E.

doi:10.1007/s10350-007-0286-6

Cited by 50 publications

(38 citation statements)

References 40 publications

(29 reference statements)

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“…Apart from SFRP2, methylation of the SFRP1 gene seems to be a suitable marker for colorectal cancer in fecal DNA; Zhang et al reported a sensitivity of 84% and specificity of 86% for this marker. However, methylation of the SFRP1 gene increased with tumor stage, suggesting that the SFRP1 marker preferentially detects colorectal cancers at higher UICC stages [53]. To identify new potential markers for aberrant DNA methylation, Mayor et al analyzed the extent and prevalence of long-range epigenetic silencing at the chromosomal region 2q14.2 and identified the gene EN1 as a target of this phenomenon.…”

Section: Stoolmentioning

confidence: 98%

Detection of DNA hypermethylation in remote media of patients with colorectal cancer: new biomarkers for colorectal carcinoma

Herbst

Kolligs

2012

Tumor Biol.

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Colorectal cancer is the third most common cancer and a major cause of cancer-related mortality. The lifetime risk to develop colorectal cancer is 6% in the Western world, and one third of the affected people will ultimately die from this disease. Colorectal carcinomas develop slowly over a period of several years. Therefore, identifying people with precancerous lesions holds the potential to reduce the incidence and mortality of colorectal cancer. Apart from mutations and chromosomal imbalances, inactivation of tumor suppressor genes by DNA hypermethylation has been recognized as an important mechanism driving colorectal carcinogenesis. In recent years, screening tests have been developed that rely on the detection of DNA hypermethylation in remote media to identify people suffering from asymptomatic colorectal cancers at early stages. Apart from their diagnostic value, methylation markers hold the potential to be used as prognostic markers. Here, we summarize the recent development of DNA methylation markers for colorectal cancer in remote media with regard to their diagnostic and prognostic value.

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Section: Stoolmentioning

confidence: 98%

Detection of DNA hypermethylation in remote media of patients with colorectal cancer: new biomarkers for colorectal carcinoma

Herbst

Kolligs

2012

Tumor Biol.

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“…29 SFRP1 methylation in stool DNA has already shown to be useful in early detection of colorectal carcinomas. 30 With this approach, SFRP4 would appear to be a good candidate for screening for precursors in the serrated neoplasia pathway. Further study is needed to elucidate WNT/bcatenin signal activation in this pathway in more detail and to confirm clinical utility of such markers because the number of cases of SSA/P with dysplastic (malignant) transformation was limited in the present study.…”

Section: Modern Pathology (2015) 28 146-158mentioning

confidence: 99%

Distinct WNT/β-catenin signaling activation in the serrated neoplasia pathway and the adenoma-carcinoma sequence of the colorectum

et al. 2015

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Sessile serrated adenoma/polyp (SSA/P) is considered as an early precursor in the serrated neoplasia pathway leading to colorectal cancer development. The conventional adenoma-carcinoma sequence is associated with activation of the WNT signaling pathway, although its role in serrated lesions is still controversial. To clarify differences in WNT signaling activation in association with MLH1 methylation or BRAF/KRAS mutations between serrated and conventional routes, we performed b-catenin immunostaining, methylation-specific PCR for MLH1 and WNT signaling associated genes such as AXIN2, APC, and MCC and secreted frizzled-related proteins (SFRPs), and direct sequencing of BRAF/KRAS in 27 SSA/Ps, 14 SSA/Ps with high-grade dysplasia and 9 SSA/Ps with submucosal carcinoma, as well as 19 conventional adenomas, 26 adenomas with high-grade dysplasia and 25 adenomas with submucosal carcinoma. Nuclear b-catenin labelings were significantly lower in the serrated series than in their adenoma counterparts, and a significant increment in those labelings was found from SSA/Ps to those with high-grade dysplasia or submucosal carcinoma. The frequency of MLH1 and SFRP4 methylation was significantly higher in SSA/P series, as compared with corresponding adenoma series. AXIN2 and MCC were more frequently methylated in SSA/Ps with high-grade dysplasia and those with submucosal carcinoma than in adenoma counterparts. Stepwise increment of AXIN2 and MCC methylation was identified from SSA/Ps through those with high-grade dysplasia to those with submucosal carcinoma. A significant correlation was seen between nuclear b-catenin expression and methylation of AXIN2 or MCC in the SSA/P series. BRAF mutation was more frequent, whereas KRAS mutation was less frequent in the SSA/P series as compared with the adenoma series. There was an inverse association of BRAF mutation with AXIN2 methylation in SSA/P series. In conclusion, WNT/b-catenin signal activation mediated by the methylation of SFRP4, MCC, and AXIN2 may make different contributions to colorectal neoplasia between the serrated and conventional routes.

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“…We have identified a cohort of 43 genes epigenetically silenced in GBM with associated promoter hypermethylation. These promoter hypermethylation patterns have also been shown to be stable, tissue-and tumor specific, and readily detectable by sensitive PCR methods Ibanez de Caceres et al, 2004;Tan et al, 2007;Zhang et al, 2007). This comprehensive identification of epigenetically regulated genes in GBM holds considerable promise for early detection, diagnosis and, potentially, prognosis in response to therapy.…”

Section: Discussionmentioning

confidence: 93%

DNA methyltransferase-mediated transcriptional silencing in malignant glioma: a combined whole-genome microarray and promoter array analysis

et al. 2009

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Epigenetic inactivation of tumor suppressor genes is a common feature in human cancer. Promoter hypermethylation and histone deacetylation are reversible epigenetic mechanisms associated with transcriptional regulation. DNA methyltransferases (DNMT1 and DNMT3b) regulate and maintain promoter methylation and are overexpressed in human cancer. We performed whole-genome microarray analysis to identify genes with altered expression after RNAi-induced suppression of DNMT in a glioblastoma multiforme (GBM) cell line. We then identified genes with both decreased expression and evidence of promoter CpG island hypermethylation in GBM tissue samples using a combined whole-genome microarray transcriptome analysis in conjunction with a promoter array analysis after DNA immunoprecipitation with anti-5-methylcytidine. DNMT1 and 3b knockdown resulted in the restored expression of 308 genes that also contained promoter region hypermethylation. Of these, 43 were also found to be downregulated in GBM tissue samples. Three downregulated genes with hypermethylated promoters and restored expression in response to acute DNMT suppression were assayed for methylation changes using bisulfite sequence analysis of the promoter region after chronic DNMT suppression. Restoration of gene expression was not associated with changes in promoter region methylation, but rather with changes in histone methylation and chromatin conformation. Two of the identified genes exhibited growth suppressive activity in in vitro assays. Combining targeted genetic manipulations with comprehensive genomic and expression analyses provides a potentially powerful new approach for identifying epigenetically regulated genes in GBM.

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DNA Stool Test for Colorectal Cancer: Hypermethylation of the Secreted Frizzled-Related Protein-1 Gene

Abstract: The results indicate that this DNA stool test of hypermethylation of the secreted frizzled-related protein-1 promoter is a sensitive and specific method. It has the potential of a clinically useful test for the early detection of colorectal cancer.

Cited by 50 publications

References 40 publications

Detection of DNA hypermethylation in remote media of patients with colorectal cancer: new biomarkers for colorectal carcinoma

Detection of DNA hypermethylation in remote media of patients with colorectal cancer: new biomarkers for colorectal carcinoma

Distinct WNT/β-catenin signaling activation in the serrated neoplasia pathway and the adenoma-carcinoma sequence of the colorectum

DNA methyltransferase-mediated transcriptional silencing in malignant glioma: a combined whole-genome microarray and promoter array analysis

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