Epigenetic IVD Tests for Personalized Precision Medicine in Cancer

Beltrán-García, Jesús; Osca-Verdegal, Rebeca; Mena-Mollá, Salvador; García-Giménez, José Luis

doi:10.3389/fgene.2019.00621

Cited by 69 publications

(45 citation statements)

References 107 publications

(137 reference statements)

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“…DNA methylation is the most well-known epigenetic modification in human disease and has been implicated in regulating the expression of a great variety of genes that are critical in cancer [7]. DNA methylation status has emerged as one of the most promising epigenetic biomarkers for several types of cancer, including BC [7,8], since it can be used in early detection and prediction of prognosis or response to treatment [9,10]. For example, O-6-Methylguanine-DNA Methyltransferase (MGMT) methylation is currently used by clinicians for routine evaluation of glioma patients' therapeutic response to temozolomide [11].…”

Section: Introductionmentioning

confidence: 99%

ADAM12 is A Potential Therapeutic Target Regulated by Hypomethylation in Triple-Negative Breast Cancer

Mendaza

Ulazia-Garmendia

Monreal-Santesteban

et al. 2020

IJMS

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Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and currently lacks any effective targeted therapy. Since epigenetic alterations are a common event in TNBC, DNA methylation profiling can be useful for identifying potential biomarkers and therapeutic targets. Here, genome-wide DNA methylation from eight TNBC and six non-neoplastic tissues was analysed using Illumina Human Methylation 450K BeadChip. Results were validated by pyrosequencing in an independent cohort of 50 TNBC and 24 non-neoplastic samples, where protein expression was also assessed by immunohistochemistry. The functional role of disintegrin and metalloproteinase domain-containing protein 12(ADAM12) in TNBC cell proliferation, migration and drug response was analysed by gene expression silencing with short hairpin RNA. Three genes (Von Willenbrand factor C and Epidermal Growth Factor domain-containing protein (VWCE), tetraspanin-9 (TSPAN9) and ADAM12) were found to be exclusively hypomethylated in TNBC. Furthermore, ADAM12 hypomethylation was associated with a worse outcome in TNBC tissues and was also found in adjacent-to-tumour tissue and, preliminarily, in plasma from TNBC patients. In addition, ADAM12 silencing decreased TNBC cell proliferation and migration and improved doxorubicin sensitivity in TNBC cells. Our results indicate that ADAM12 is a potential therapeutic target and its hypomethylation could be a poor outcome biomarker in TNBC.

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Section: Introductionmentioning

confidence: 99%

ADAM12 is A Potential Therapeutic Target Regulated by Hypomethylation in Triple-Negative Breast Cancer

Mendaza

Ulazia-Garmendia

Monreal-Santesteban

et al. 2020

IJMS

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“…Remarkably, in the end of 2017, the "Epi proLung ® " assay, developed by Epigenomics AG, based on these two genes received the Conformité Européenne (CE) mark for In Vitro Diagnostic (IVD) test. According to their validation study comprising 360 patients from the US and Europe, of which 152 were diagnosed with LC, depending on the Epi proLung ® test score threshold chosen, 85% sensitivity was achieved for 50% specificity, whereas sensitivity decreased to 59% if 95% specificity was considered [40,41].…”

Section: Screening and Diagnosismentioning

confidence: 99%

“…SEPT9 me is the mostly reported methylated gene in blood from CRC patients. Remarkably, this marker was the first blood-based IVD assay for detection of occult cancer based on an epigenetic alteration, approved by the US Food and Drug Administration (FDA) in 2016, under the designation "Epi ProColon ® 2.0" (Epigenomics AG) [40]. Additionally, this CE-IVD marked test is also commercially available in Europe and China [112].…”

Section: Screening and Diagnosismentioning

confidence: 99%

DNA Methylation-Based Testing in Liquid Biopsies as Detection and Prognostic Biomarkers for the Four Major Cancer Types

Constâncio

Nunes

Henrique

et al. 2020

Cells

138

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Lung, breast, colorectal, and prostate cancers are the most incident worldwide. Optimal population-based cancer screening methods remain an unmet need, since cancer detection at early stages increases the prospects of successful and curative treatment, leading to a lower incidence of recurrences. Moreover, the current parameters for cancer patients’ stratification have been associated with divergent outcomes. Therefore, new biomarkers that could aid in cancer detection and prognosis, preferably detected by minimally invasive methods are of major importance. Aberrant DNA methylation is an early event in cancer development and may be detected in circulating cell-free DNA (ccfDNA), constituting a valuable cancer biomarker. Furthermore, DNA methylation is a stable alteration that can be easily and rapidly quantified by methylation-specific PCR methods. Thus, the main goal of this review is to provide an overview of the most important studies that report methylation biomarkers for the detection and prognosis of the four major cancers after a critical analysis of the available literature. DNA methylation-based biomarkers show promise for cancer detection and management, with some studies describing a “PanCancer” detection approach for the simultaneous detection of several cancer types. Nonetheless, DNA methylation biomarkers still lack large-scale validation, precluding implementation in clinical practice.

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“…Aberrant methylation in the promoter regions of tumor suppressor genes is associated with carcinogenesis via transcriptional silencing of gene expression, resulting in the onset and development of cancer. [21] RASSF1A promoter methylation provides significant prognostic information in early- [7,23] In another study, Jezkova et al found that RASSF1A hypermethylation occurred in 92.2% of the cases. [24] In the present study, we found that RASS-F1A methylation was 96.6%.…”

Section: Rassf1a/apc Methylationmentioning

confidence: 99%

Correlation of HER2/TOP2A Gene Aberrations with RASSF1A/APC Gene Methylation Status in High-Risk Breast Cancer

NURSAL

2020

TJ Oncol

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Breast cancer (BC) is a heterogeneous malignancy and differs widely among different patients. The aim of this study was to investigate the relationship between the HER2/TOP2A gene aberrations and promoter methylation in RASSF1A/APC genes in patients with high-risk BC. METHODS Formalin-fixed paraffin embedded (FFPE) tissue samples from primary breast tumors (n=60) were assessed. HER2/TOP2A aberrations was evaluated using FISH method. DNA was extracted from FFPE tumor tissues, and Methylation-sensitive high resolution melting (MS-HRM) analysis were performed for RASSF1A/APC genes methylation status. RESULTS HER2 amplification and TOP2A aberration were observed in 15/60 (25%) and 18/60 (30%) cases, respectively. According to the statistical analysis, HER2 amplification was associated with higher tumor grade (p=0.001), PR status (p=0.025), and TOP2A aberrations (p=0.004). RASSF1A and APC methylation were 58/60 (96.6%) and 26/60 (43.3%), respectively. There was a significant correlation between APC methylation and TOP2A aberration. APC gene methylation was significantly more frequent in tumors with TOP2A aberration (p=0.026). CONCLUSION Our results suggested that APC gene promoter hypermethylation was associated with TOP2A gene aberrations in patients with high-risk BC. This may be significant for targeted individual therapy. Additionally, it was confirmed that there was significant association of TOP2A gene aberrations with the HER2 gene amplification seen in BC.

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Epigenetic IVD Tests for Personalized Precision Medicine in Cancer

Cited by 69 publications

References 107 publications

ADAM12 is A Potential Therapeutic Target Regulated by Hypomethylation in Triple-Negative Breast Cancer

ADAM12 is A Potential Therapeutic Target Regulated by Hypomethylation in Triple-Negative Breast Cancer

DNA Methylation-Based Testing in Liquid Biopsies as Detection and Prognostic Biomarkers for the Four Major Cancer Types

Correlation of HER2/TOP2A Gene Aberrations with RASSF1A/APC Gene Methylation Status in High-Risk Breast Cancer

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