Tumor-derived aberrant methylation in plasma of invasive ductal breast cancer patients: Clinical implications

Hu, Xichun; Wong, Ivy; Chow, Louis W C

doi:10.3892/or.10.6.1811

Cited by 26 publications

(22 citation statements)

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“…Additionally, circulating DNA fragments have limited stability, and hypermethylation is not a fixed event (24). This would partially explain the differences in the methylation frequencies of the same gene between tumor tissues and plasma, which has been shown in this study as well as other reports (7～11, 14,15).…”

Section: Discussionsupporting

confidence: 68%

“…This panel of genes was somewhat less effective at detecting hypermethylated DNA in the peripheral circulation of breast cancer patients; however, an overall sensitivity of 67% was observed for the 33 patients with tumors showing hypermethylation for at least one of the genes compared to two other panels (APC, RASSF1A, DAP-K) (14) and (p16 and CDH1) (15), with 76 and 82% sensitivities, respectively. This can likely be attributed to differences in PCR amplification efficiencies between the primer sets and laboratories, as two panels-(cyclin D2, RARβ, twist and HIN-1) and (APC, RASSF1A, DAP-K)-provided similar diagnostic coverage (97% and 94%, respectively) in the corresponding tumors.…”

Section: Discussionmentioning

confidence: 99%

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Gene Promoter Hypermethylation in Tumors and Plasma of Breast Cancer Patients

et al. 2005

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Purpose: To measure the hypermethylation of four genes in primary tumors and paired plasma samples to determine the feasibility of gene promoter hypermethylation markers for detecting breast cancer in the plasma.Materials and Methods: DNA was extracted from the tumor tissues and peripheral blood plasma of 34 patients with invasive breast cancer, and the samples examined for aberrant hypermethylation in cyclin D2, retinoic acid receptor β (RARβ), twist and high in normal-1 (HIN-1) genes using methylation-specific PCR (MSP), and the results correlated with the clinicopathological parameters.Results: Promoter hypermethylation was detected at high frequency in the primary tumors for cyclin D2 (53% ), RARβ (56% ), twist (41%) and HIN-1 (77% ). Thirty-three of the 34 (97% ) primary tumors displayed promoter hypermethylation in at least one of the genes examined. The corresponding plasma samples showed hyperme thylation of the same genes, although at lower frequencies (6% for cyclin D2, 16% for RARβ, 36% for twist, and 54% for HIN-1).

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Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Gene Promoter Hypermethylation in Tumors and Plasma of Breast Cancer Patients

et al. 2005

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“…Recently, several groups, using a panel of multiple genes which are well known to be tumorassociated, have demonstrated the prevalence of methylation positive genes in sera or plasma from breast cancer patients (20)(21)(22)(23)(24)(25)(26)(27). Nevertheless, current multiple gene panel assays still lack the necessary sensitivity for application in the clinical setting.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide identification of OTP gene as a novel methylation marker of breast cancer

Kim¹,

Lee

Oh³

et al. 2012

Oncol Rep

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Abstract. Aberrant DNA methylation occurs early and frequently in tumorigenesis. Identification of DNA methylation biomarkers is a field that provides potential for improving the clinical process of breast cancer diagnosis. We utilized a genome-wide technique, methylated DNA isolation assay (MeDIA), in combination with high-resolution CpG microarray analysis to identify hypermethylated genes in breast cancer. Among differentially methylated genes between tumor and adjacent normal tissues, 3 candidate genes (LHX2, WT1 and OTP) were finally selected through a step-wise filtering process and examined for methylation status in normal tissues, primary tumor, and paired adjacent normal-appearing tissues from 39 breast cancer patients. Based on the calculated cut-off values, all genes showed significantly higher frequencies of aberrant hypermethylation in primary tumors (43.6% for LHX2, 89.7% for WT1 and 100% for OTP, P<0.05) while frequencies were intermediate in paired adjacent normal tissues and absent in normal tissues. On further analysis, the methylation level in primary tumors was not significantly correlated with clinicopathological features. Interestingly, DNA methylation of a novel gene OTP was detected in adjacent normal tissues even 6 cm away from primary tumors, suggesting that OTP methylation may qualify as a biomarker for the early detection of breast cancer. In conclusion, we successfully identified a novel gene OTP frequently methylated in breast cancer by genomewide screening. Our results suggest that the OTP gene may play a crucial role in breast carcinogenesis, although further clinical validation will be needed to evaluate the potential application of OTP in the early detection of breast cancer.

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“…However, methylation of the CDKN2A and CDKN2B promoters has been reported in leukemia (Herman et al, 1997;Chim et al, 2003;Kusy et al, 2004) and other tumor types (Hu et al, 2003;Furonaka et al, 2004). Interestingly, preferential deletion of maternally derived alleles has been reported (Heyman et al, 1993;Morison et al, 2002) in ALL, and a DMR [DMR (2-48)] has been reported on 9p (Strichman-Almashanu et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Detailed methylation analysis of CpG islands on human chromosome region 9p21

Weeks

Morison

2005

Genes Chromosomes & Cancer

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Deletion of 9p21 is the most commonly reported chromosomal abnormality in pediatric acute lymphoblastic leukemia, and published data suggest that the maternal chromosome is preferentially deleted. Preferential maternal deletion of 9p21 and reports of a differentially methylated region (DMR) and of parental effects in mice with lymphoma suggest there may be an unrecognized imprinted locus in this region. To screen for DMRs, we used the mcrBC/HpaII screening method and peripheral-blood DNA. Of 36 CpG islands within an 8.5-Mb region of 9p21, seven were identified as putative DMRs and were further analyzed by bisulfite sequencing. Neither any of the CpG islands nor a previously published putative DMR nearby showed evidence of differential parental methylation; however, the published DMR did demonstrate sequence-dependent differential methylation. Our data, which showed heterogeneous and low-level methylation of CpG islands, have obvious implications for methylation studies.

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Tumor-derived aberrant methylation in plasma of invasive ductal breast cancer patients: Clinical implications

Cited by 26 publications

References 0 publications

Gene Promoter Hypermethylation in Tumors and Plasma of Breast Cancer Patients

Gene Promoter Hypermethylation in Tumors and Plasma of Breast Cancer Patients

Genome-wide identification of OTP gene as a novel methylation marker of breast cancer

Detailed methylation analysis of CpG islands on human chromosome region 9p21

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