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- Wojdacz, TK
(författare)
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Biological and methodological aspects of assessment of locus specific de novo methylation in blood
- 2015
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Ingår i: Biomarkers in medicine. - : Future Medicine Ltd. - 1752-0371 .- 1752-0363. ; 9:12, s. 1291-1299
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Locus-specific methylation in blood differs between individuals. As those changes may represent de novo methylation, induced by environmental factors, we aimed to evaluate the biological and methodological limitations of detection of methylation in blood. Materials & methods: We used Methylation-Sensitive High Resolution Melting to analyze methylation at 21 gene loci in peripheral blood DNA samples from 203 healthy women. Results: Overall nine of the screened loci displayed marked inter-individual variation in methylation frequency with methylation levels predominantly around 1%. The methylation of specific loci showed different association with age and reproducibility of detection. Conclusions: Our results allowed benchmarking of both technological and biological limitations that need to be accounted for when evaluating locus specific methylation in blood as potential biomarker.
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- Wojdacz, TK, et al.
(författare)
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Clinical significance of DNA methylation in chronic lymphocytic leukemia patients: results from 3 UK clinical trials
- 2019
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Ingår i: Blood advances. - : American Society of Hematology. - 2473-9537 .- 2473-9529. ; 3:16, s. 2474-2481
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Tidskriftsartikel (refereegranskat)abstract
- Chronic lymphocytic leukemia patients with mutated immunoglobulin heavy-chain genes (IGHV-M), particularly those lacking poor-risk genomic lesions, often respond well to chemoimmunotherapy (CIT). DNA methylation profiling can subdivide early-stage patients into naive B-cell–like CLL (n-CLL), memory B-cell–like CLL (m-CLL), and intermediate CLL (i-CLL), with differing times to first treatment and overall survival. However, whether DNA methylation can identify patients destined to respond favorably to CIT has not been ascertained. We classified treatment-naive patients (n = 605) from 3 UK chemo and CIT clinical trials into the 3 epigenetic subgroups, using pyrosequencing and microarray analysis, and performed expansive survival analysis. The n-CLL, i-CLL, and m-CLL signatures were found in 80% (n = 245/305), 17% (53/305), and 2% (7/305) of IGHV-unmutated (IGHV-U) cases, respectively, and in 9%, (19/216), 50% (108/216), and 41% (89/216) of IGHV-M cases, respectively. Multivariate Cox proportional analysis identified m-CLL as an independent prognostic factor for overall survival (hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.24-0.87; P = .018) in CLL4, and for progression-free survival (HR, 0.25; 95% CI, 0.10-0.57; P = .002) in ARCTIC and ADMIRE patients. The analysis of epigenetic subgroups in patients entered into 3 first-line UK CLL trials identifies m-CLL as an independent marker of prolonged survival and may aid in the identification of patients destined to demonstrate prolonged survival after CIT.
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- Wojdacz, TK, et al.
(författare)
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Exposure to arsenic and intra-chromosomal instability in blood
- 2014
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Ingår i: Metallomics : integrated biometal science. - : Oxford University Press (OUP). - 1756-591X. ; 6:8, s. 1387-1389
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Tidskriftsartikel (refereegranskat)abstract
- The 450k Chip Analysis Methylation Pipeline (ChAMP) is a novel Illumina Infinium HumanMethylation450 BeadChip data processing algorithm that allows the analysis of copy number alterations (CNAs).
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