Characterisation and reproducibility of the HumanMethylationEPIC v2.0 BeadChip for DNA methylation profiling

Peters, Timothy J.; Meyer, Braydon; Ryan, Lauren; Achinger-Kawecka, Joanna; Song, Jenny; Campbell, Elyssa M.; Qu, Wenjia; Nair, Shalima; Loi-Luu, Phuc; Stricker, Phillip; Lim, Elgene; Stirzaker, Clare; Clark, Susan J.; Pidsley, Ruth

doi:10.1186/s12864-024-10027-5

Cited by 4 publications

(1 citation statement)

References 55 publications

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“…We used NGS-based targeted resequencing and Sanger sequencing for clinical validation of ZNF G64A mutation as AP-/BC-CML. Targeted resequencing and Sanger sequencing along with other similar techniques are routinely being used for clinical validation of molecular biomarkers [38][39][40][41][42][43][44][45].…”

Section: Discussionmentioning

confidence: 99%

A retrospective case-control study for Clinical Validation of mutated ZNF208 as a novel biomarker of fatal blast crisis in Chronic Myeloid Leukemia

Alanazi,

Siyal,

Basit

et al. 2024

Preprint

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The hallmark of Chronic Myeloid Leukemia (CML) is Philadelphia chromosome t(9:22), which leads to formation of BCR-ABL1 fusion oncogene. BCR-ABL1 induces genetic instability, causing the progression of chronic myeloid leukemia (CML) from the manageable Chronic Phase (CP-CML) to the accelerated phase (AP-CML) and ultimately to the lethal blast crisis (BC-CML). The precise mechanism responsible for CML progression are not well comprehended, and there is a lack of specific molecular biomarkers for advanced phase CML. Mutations in transcription factors (TFs) have a significant role in cancer initiation, relapses, invasion, metastasis, and resistance to anti-cancer drugs. Recently, our group reported association of a novel transcription factor, ZNF208, with CML progression and there was a dire need for clinical validation of this novel biomarker. Therefore, the aim of this study was to clinically validate mutated ZNF208 as a novel biomarker for CML progression in a larger cohort of AP- and BC-CML patients using control-case studies. A total of 73 CML patients (N=73) from King Saud University Medical City Riyadh and King Abdulaziz National Guard Hospital, Al-Ahsa, Saudi Arabia were enrolled in the study (2020-2023) , with the experimental group (cases) consisting of patients AP-CML (n=20) and BC-CML (n=12). The controls consisted of age/sex matched CP-CML (n=41). The study was approved by Research Ethics Committees of participating institutes and all patients provided informed consent for the study. Clinical evaluations for patients were conducted according to the guidelines established by the European LeukemiaNet in 2020. Targeted resequencing of ZNF 208 was employed using Illumina NextSeq500 instrument (Illumina, San Diego, CA, USA) and mutations confirmed using Sanger sequencing. Both next generation sequencing as well as Sanger sequencing identified a novel missense mutation (c.64G>A) in novel ZNF208 . in 56 (93.3) and12 (100) CP-, AP- and BC-CML patients respectively, while in none (0%) of CP-CML patients or healthy controls from genomic databases (p=0.0001). Therefore, our studies show that ZNF208 mutation (c.64G>A) is novel and very specific biomarker for AP-and BC-CML patients. ZNF208 and other such proteins may cause carcinogenesis by interacting with KAP-1 repressor to silence many target genes and thus may prove to be novel drug targets as well. Therefore, we recommend carrying out prospective clinical trials for further clinical validation of this biomarker for its utilization in clinical decision, investigating its precise role in cancer pathogenesis and investigate its potential for novel drug target in advanced phase CML patients.

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Section: Discussionmentioning

confidence: 99%

A retrospective case-control study for Clinical Validation of mutated ZNF208 as a novel biomarker of fatal blast crisis in Chronic Myeloid Leukemia

Alanazi,

Siyal,

Basit

et al. 2024

Preprint

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Rare Turner syndrome and lupus coexistence with insights from DNA methylation patterns

Kavrul Kayaalp,

Casares-Marfil,

Şahin

et al. 2024

Clinical Immunology

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Discrepancies in readouts between Infinium MethylationEPIC v2.0 and v1.0 reflected in DNA methylation-based tools: implications and considerations for human population epigenetic studies

Zhuang,

Jude,

Konwar

et al. 2024

Preprint

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BackgroundThe recently launched DNA methylation profiling platform, Illumina MethylationEPIC BeadChip Infinium microarray v2.0 (EPICv2), is highly correlated with measurements obtained from its predecessor MethylationEPIC BeadChip Infinium microarray v1.0 (EPICv1). However, the concordance between the two versions in the context of DNA methylation-based tools, including cell type deconvolution algorithms, epigenetic clocks, and inflammation and lifestyle biomarkers has not yet been investigated.FindingsWe profiled DNA methylation on both EPIC versions using matched venous blood samples from individuals spanning early to late adulthood across three cohorts. On combining the DNA methylomes of the cohorts, we observed that samples primarily clustered by the EPIC version they were measured on. Within each cohort, when we calculated cell type proportions, epigenetic age acceleration (EAA), rate of aging estimates, and biomarker scores for the matched samples on each version, we noted significant differences between EPICv1 and EPICv2 in the majority of these estimates. These differences were not significant, however, when estimates were adjusted for EPIC version or when EAAs were calculated separately for each EPIC version.ConclusionsOur findings indicate that EPIC version differences predominantly explain DNA methylation variation and influence estimates of DNA methylation-based tools, and therefore we recommend caution when combining cohorts run on different versions. We demonstrate the importance of calculating DNA methylation-based estimates separately for each EPIC version or accounting for EPIC version either as a covariate in statistical models or by using version correction algorithms.

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Characterisation and reproducibility of the HumanMethylationEPIC v2.0 BeadChip for DNA methylation profiling

Cited by 4 publications

References 55 publications

A retrospective case-control study for Clinical Validation of mutated ZNF208 as a novel biomarker of fatal blast crisis in Chronic Myeloid Leukemia

A retrospective case-control study for Clinical Validation of mutated ZNF208 as a novel biomarker of fatal blast crisis in Chronic Myeloid Leukemia

Rare Turner syndrome and lupus coexistence with insights from DNA methylation patterns

Discrepancies in readouts between Infinium MethylationEPIC v2.0 and v1.0 reflected in DNA methylation-based tools: implications and considerations for human population epigenetic studies

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