<i>DFNA5</i>promoter methylation a marker for breast tumorigenesis

Croes, Lieselot; Beeck, Ken Op de; Pauwels, Patrick; Berghe, Wim Vanden; Peeters, Marc; Fransén, Erik; Camp, Guy Van

doi:10.18632/oncotarget.16654

Cited by 39 publications

(50 citation statements)

References 42 publications

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“…However, in this study, we considered CpG06301139 still part of the upstream promoter region because the methylation pattern is clearly different from the other promoter CpGs and it is located 24 base pairs from the border of the flanking region of the DFNA5 promoter. In addition to the 22 CpGs analyzed in this study (green dots), the four CpGs analyzed in our previous study (pink dots, [ 36 ]) and the TaqMan probe (6FAM 5′-ATTCGACCCCGCGAAAAAACGCCGCT-3′-TAMRA) of the study of Kim et al (blue dot, [ 35 ]) are annotated. The transcription start site and the translation start site are indicated with an orange dot and a red dot, respectively …”

Section: Methodsmentioning

confidence: 99%

“…Epigenetic silencing through DFNA5 methylation was previously shown in gastric [ 31 ], colorectal [ 32 , 34 ], and breast cancer [ 35 ] on a limited number of samples. Recently, we performed methylation analysis on four CpGs in the DFNA5 promoter region using bisulphite pyrosequencing on 123 primary breast adenocarcinomas, 16 histologically normal breast tissues adjacent to the tumor, and 24 breast reduction tissues from women without cancer [ 36 ] (Fig. 2 ).…”

Section: Introductionmentioning

confidence: 99%

“…Significantly higher methylation percentages were seen in the adenocarcinoma samples compared to those in the healthy breast reduction samples. A receiver operating characteristic (ROC) curve for DFNA5 methylation showed a sensitivity of 61.8% for the detection of breast cancer with a specificity of 100% [ 36 ]. We concluded that DFNA5 methylation shows strong potential as biomarker for detection of breast cancer.…”

Section: Introductionmentioning

confidence: 99%

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Large-scale analysis of DFNA5 methylation reveals its potential as biomarker for breast cancer

et al. 2018

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BackgroundBreast cancer is the most frequent cancer among women worldwide. Biomarkers for early detection and prognosis of these patients are needed. We hypothesized that deafness, autosomal dominant 5 (DFNA5) may be a valuable biomarker, based upon strong indications for its role as tumor suppressor gene and its function in regulated cell death. In this study, we aimed to analyze DFNA5 methylation and expression in the largest breast cancer cohort to date using publicly available data from TCGA, in order to further unravel the role of DFNA5 as detection and/or prognostic marker in breast cancer. We analyzed Infinium HumanMethylation450k data, covering 22 different CpGs in the DFNA5 gene (668 breast adenocarcinomas and 85 normal breast samples) and DFNA5 expression (Agilent 244K Custom Gene Expression: 476 breast adenocarcinomas and 56 normal breast samples; RNA-sequencing: 666 breast adenocarcinomas and 71 normal breast samples).ResultsDFNA5 methylation and expression were significantly different between breast cancer and normal breast samples. Overall, breast cancer samples showed higher DFNA5 methylation in the putative gene promoter compared to normal breast samples, whereas in the gene body and upstream of the putative gene promoter, the opposite is true. Furthermore, DFNA5 methylation, in 10 out of 22 CpGs, and expression were significantly higher in lobular compared to ductal breast cancers. An important result of this study was the identification of a combination of one CpG in the gene promoter (CpG07504598) and one CpG in the gene body (CpG12922093) of DFNA5, which was able to discriminate between breast cancer and normal breast samples (AUC = 0.93). This model was externally validated in three independent datasets. Moreover, we showed that estrogen receptor state is associated with DFNA5 methylation and expression. Finally, we were able to find a significant effect of DFNA5 gene body methylation on a 5-year overall survival time.ConclusionsWe conclude that DFNA5 methylation shows strong potential as detection and prognostic biomarker for breast cancer.Electronic supplementary materialThe online version of this article (10.1186/s13148-018-0479-y) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Large-scale analysis of DFNA5 methylation reveals its potential as biomarker for breast cancer

et al. 2018

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“…In some early abnormalities during the process of tumorigenesis, epigenetic changes often occur, possibly leading to gene changes associated with tumourigenesis . DNA methylation is a major area of interest within the field of epigenetic modifications regulating gene transcription and expression, which is of great importance in tumorigenesis . Evidence suggests that DNA methylation is among the most important factors for many cellular processes, such as DNA damage repair, cell cycle regulation, angiogenesis, and apoptosis .…”

Section: Introductionmentioning

confidence: 99%

Analysis of methylation‐driven genes for predicting the prognosis of patients with head and neck squamous cell carcinoma

Pan

Song

Cheng

et al. 2019

J of Cellular Biochemistry

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To help provide evidence for prognosis prediction and personalized targeted therapy for patients with head and neck squamous cell carcinoma (HNSCC), we investigated prognosis-specific methylation-driven genes in HNSCC. Survival time data, RNA sequencing data, and methylation data for HNSCC patients were downloaded from The Cancer Genome Atlas. The MethylMix R package based on the β mixture model was utilized to screen genes with different methylation statuses in tumor tissues and adjacent normal tissues, and a total of 182 HNSCC-related methylation-driven genes were then identified. A survival prediction scoring model based on multivariate Cox analysis was developed to screen the genes related to the prognosis of HNSCC, and a linear risk model of the methylation status of six genes (INA, LINC01354, TSPYL4, MAGEB2, EPHX3, and ZNF134) was constructed. The prognostic values of the six genes were further independently explored by survival analysis combined with methylation and gene expression analyses. The 5-year survival rate in the highrisk group of patients in the test set was 30.4% (95% CI: 22.7%-40.8%) and that in the low-risk group of patients was 65.5% (95% CI: 56.1%-76.5%). The area under the receiver operating characteristic curve for the model was 0.723, which further verified the specificity and sensitivity of the model. In addition, subsequent combined survival analysis revealed that all six genes could be used as independent prognostic markers and thus might be potential drug targets. The innovative method provides new insight into the molecular mechanism and prognosis of HNSCC. K E Y W O R D SDNA methylation-driven genes, epigenetics, HNSCC, prognostic risk model, survival analysis

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“…Epigenetic modifications have been documented contributing to the carcinogenesis of many human cancers [ 3 , 4 ]. As one predominant modification of epigenetics, DNA methylation, plays a major role during the tumorigenesis of CRC [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Methylatedclaudin-11associated with metastasis and poor survival of colorectal cancer

Zhou

et al. 2017

Oncotarget

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As one of crucial epigenetic modification, DNA methylation plays an important role during the carcinogenesis of colorectal cancer (CRC). In the current study, we used a human genome methylation array to detect the aberrant methylation genes in CRC. We further identified the hypermethylation of claudin-11 (CLDN11) and proved inverse correlation between CLDN11 methylation and its expression in CRC. In vitro experiments showed debased migration ability of colonic cancer cells in accompany with the converted methylation of CLDN11 after colonic cancer cells treated with demethylation agent, 5-aza-2’-deoxycytidine. Besides, our results also represented that hypermethylation of CLDN11 was associated with increased metastatic potential of CRC and with low progression free survival (PFS) of CRC. In conclusion, our findings supported that the hypermethylated CLDN11 is associated with metastasis of CRC and prognosis of poor survival of CRC.

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DFNA5promoter methylation a marker for breast tumorigenesis

Cited by 39 publications

References 42 publications

Large-scale analysis of DFNA5 methylation reveals its potential as biomarker for breast cancer

Large-scale analysis of DFNA5 methylation reveals its potential as biomarker for breast cancer

Analysis of methylation‐driven genes for predicting the prognosis of patients with head and neck squamous cell carcinoma

Methylatedclaudin-11associated with metastasis and poor survival of colorectal cancer

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