Hypermethylated APC DNA in Plasma and Prognosis of Patients With Esophageal Adenocarcinoma

Kawakami, Kazuyuki; Brabender, Jan; Lord, Reginald V.; Groshen, Susan; Greenwald, Bruce D.; Krasna, Mark J.; Yin, Jing; Fleisher, A. Steven; Abraham, John M.; Beer, David G.; Sidransky, David; Huss, Harold T.; DeMeester, Tom R.; Eads, Cindy A.; Laird, Peter W.; Ilson, David H.; Kelsen, David P.; Harpole, David H.; Moore, Mary B.; Danenberg, Kathleen D.; Danenberg, Peter V.; Meltzer, Stephen J.

doi:10.1093/jnci/92.22.1805

Cited by 322 publications

(195 citation statements)

References 31 publications

Supporting

Mentioning

175

Contrasting

Unclassified

Order By: Relevance

“…The high level of methylation on CpG sites of the IRX1 promoter was associated with a transcriptional block. Epigenetic events, especially promoter methylation, are now widely accepted causes of gene silencing (Kawakami et al, 2000;Robertson and Jones, 2000;Garinis et al, 2002;Momparler, 2003;Choi and Wu, 2005;Toyota and Issa, 2005;Esteller, 2007;Jee et al, 2009). 5-Aza-dC is a methyltransferase inhibitor that is widely used to restore gene expression (Bergman and Mostoslavsky, 1998;Tycko, 2000;Yamashita et al, 2002;Shaker et al, 2004;Hellebrekers et al, 2007;Schneider-Stock and Ocker, 2007;Hurtubise et al, 2008;Lemaire et al, 2008;Cairns, 2009).…”

Section: Discussionmentioning

confidence: 99%

“…Identifying novel serological biomarkers with higher specificity and sensitivity is eagerly desired for gastric cancer. Recent data showed that the presence of tumor-associated alterations (such as promoter hypermethylation) have been described in the plasma DNA from patients with various kinds of cancer (Kawakami et al, 2000;Duffy et al, 2009). DNA methylation may provide a new generation of cancer biomarkers in the next decade (Duffy et al, 2009;Tommasi et al, 2009).…”

Section: Irx1 Gene In Gastric Carcinomamentioning

confidence: 99%

See 1 more Smart Citation

Homeobox gene IRX1 is a tumor suppressor gene in gastric carcinoma

et al. 2010

View full text Add to dashboard Cite

The IRX1 tumor suppressor gene is located on 5p15.33, a cancer susceptibility locus. Loss of heterozygosity of 5p15.33 in gastric cancer was identified in our previous work. In this study, we analyzed the molecular features and function of IRX1. We found that IRX1 expression was lost or reduced in gastric cancer. However, no mutations were identified in IRX1-encoding regions. IRX1 transcription was suppressed by hypermethylation, and the expression of IRX1 mRNA was partially restored in gastric cancer cells after 5-Aza-dC treatment. Restoring IRX1 expression in SGC-7901 and NCI-N87 gastric cancer cells inhibited growth, invasion and tumorigenesis in vitro and in vivo. We identified a number of target genes by global microarray analysis after IRX1 transfection combined with real-time PCR and chromatin immunoprecipitation assay. BDKRB2, an angiogenesis-related gene, HIST2H2BE and FGF7, cell proliferation and invasionrelated genes, were identified as direct IRX1 target genes. The hypermethylation of IRX1 was not only detected in primary gastric cancer tissues but also in the peripheral blood of gastric cancer patients, suggesting IRX1 could potentially serve as a biomarker for gastric cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Irx1 Gene In Gastric Carcinomamentioning

confidence: 99%

Homeobox gene IRX1 is a tumor suppressor gene in gastric carcinoma

et al. 2010

View full text Add to dashboard Cite

show abstract

“…The discovery of circulating cell-free DNA in serum or plasma (15,(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)) presents a new opportunity for identifying MGMT promoter methylation in tumor cells. There have been limited reports on the concordance between serum, plasma, or sputum and tumor methylation biomarkers in patients, such as APC promoter methylation in lung cancer (29); hMLH1 promoter methylation in CRC (23); p16 methylation in NSCLC, H&N, esophageal, breast, and hepatocellular cancers (15,24,28,30,32); and MGMT methylation in lung cancer (44).…”

Section: Discussionmentioning

confidence: 99%

“…It is now recognized that cell-free tumor DNA shed into the bloodstream may be detectable (15,(23)(24)(25)(26)(27)(28)(29)(30)(31)(32). Recently, promoter methylation status determined in serum DNA isolates from patients with cancer has been shown to highly correlate with methylation status in those patients' tumors (24-27, 30, 32).…”

Section: Introductionmentioning

confidence: 99%

A Phase II Study of Temozolomide in Patients with Advanced Aerodigestive Tract and Colorectal Cancers and Methylation of theO6-Methylguanine-DNA Methyltransferase Promoter

Hochhauser

Glynne‐Jones

Potter

et al. 2013

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

Responses of patients with gliomas to temozolomide are determined by O 6 -methylguanine-DNA methyltransferase (MGMT) and mismatch repair (MMR) pathways. This phase II study (NCT00423150) investigated whether MGMT promoter methylation predicts response in patients with advanced aerodigestive tract and colorectal cancers (CRC). Tumor and serum samples were screened for MGMT promoter methylation. In methylation-positive patients, 150 mg/m 2 temozolomide was administered daily on a seven-day-on, sevenday-off schedule for each 28-day cycle. The primary efficacy endpoint was response rate (RR). MMR status was determined by a microsatellite instability assay. Among 740 patients screened, 86 were positive for MGMT promoter methylation and enrolled. Nineteen percent of the screened population (137/740) had confirmed tissue and/or serum MGMT promoter methylation, including 25% (57 of 229) for CRC, 36% (55 of 154) for esophageal cancer, 11% (12 of 113) for head and neck cancer, and 5% (13 of 242) for non-small cell lung carcinoma. Among patients with valid methylation results in both tissue and serum samples, concordance was 81% (339 of 419). The majority of enrolled patients (69 of 86; 80%) had microsatellite stable cancer. Overall RR was 6% (5 of 86 partial responses); all responders had microsatellite stable cancer. Temozolomide resulted in low RRs in patients enriched for MGMT methylation. MGMT methylation status varied considerably in the patient population. Although serum methylation assay is an option for promoter methylation detection, tissue assay remains the standard for methylation detection. The low RR of this cohort of patients indicates that MGMT methylation as a biomarker is not applicable to heterogeneous tumor types, and tumor-specific factors may override validated biomarkers. Mol Cancer Ther; 12(5); 809-18. Ó2013 AACR.

show abstract

“…In these situations the quantity and methylation status of DNA regions derived from oncogenes or tumour suppressor genes provide biomarkers for disease progression and prognosis [1]. The changes in DNA methylation status indicate changes in gene expression of the relevant biomarker genes; for example, hypermethylated APC gene DNA in plasma may be a useful biomarker of aggressive disease in esophageal adenocarcinoma patients [7]. In pregnancy, a proportion (typically 3-6%) of the cell-free DNA in maternal plasma is of fetal genotype, originating largely from the placenta [8,9].…”

Section: Introductionmentioning

confidence: 99%

Methylation of the imprinted GNAS1 gene in cell-free plasma DNA: equal steady-state quantities of methylated and unmethylated DNA in plasma

Puszyk

Chatha

Elsenheimer

et al. 2009

Clinica Chimica Acta

View full text Add to dashboard Cite

However, the production and clearance of cell-free DNA from plasma in relation to its methylation status, are poorly understood processes. Methods:We studied the methylation status of DNA derived from the imprinted GNAS1 locus, in cell-free plasma DNA of healthy adults. Heterozygotes were identified that carried the SNP rs1800905 in the imprinted region. The parent-oforigin-dependent DNA methylation was analysed by bisulfite conversion, followed by cloning and sequencing.Results: Genomic DNA molecules derived from both the methylated, maternal, allele and the unmethylated, paternal, allele were found in plasma. Methylated and unmethylated DNA molecules were present in equal numbers. Conclusions:Our data indicate that the methylation status of a DNA sequence has no effect on its steady state concentration in the cell-free DNA component of plasma, in healthy adults.2

show abstract

Hypermethylated APC DNA in Plasma and Prognosis of Patients With Esophageal Adenocarcinoma

Cited by 322 publications

References 31 publications

Homeobox gene IRX1 is a tumor suppressor gene in gastric carcinoma

Homeobox gene IRX1 is a tumor suppressor gene in gastric carcinoma

A Phase II Study of Temozolomide in Patients with Advanced Aerodigestive Tract and Colorectal Cancers and Methylation of theO6-Methylguanine-DNA Methyltransferase Promoter

Methylation of the imprinted GNAS1 gene in cell-free plasma DNA: equal steady-state quantities of methylated and unmethylated DNA in plasma

Contact Info

Product

Resources

About