Diagnosis and Prognostication of Ductal Adenocarcinomas of the Pancreas Based on Genome-Wide DNA Methylation Profiling by Bacterial Artificial Chromosome Array-Based Methylated CpG Island Amplification

To establish diagnostic criteria for ductal adenocarcinomas of the pancreas (PCs), bacterial artificial chromosome (BAC) array-based methylated CpG island amplification was performed using 139 tissue samples. Twelve BAC clones, for which DNA methylation status was able to discriminate cancerous tissue (T) from noncancerous pancreatic tissue in the learning cohort with a specificity of 100%, were identified. Using criteria that combined the 12 BAC clones, T-samples were diagnosed as cancers with 100% sensitivity and specificity in both the learning and validation cohorts. DNA methylation status on 11 of the BAC clones, which was able to discriminate patients showing early relapse from those with no relapse in the learning cohort with 100% specificity, was correlated with the recurrence-free and overall survival rates in the validation cohort and was an independent prognostic factor by multivariate analysis. Genome-wide DNA methylation profiling may provide optimal diagnostic markers and prognostic indicators for patients with PCs.

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Genome-wide DNA methylation profiling with MeDIP-seq using archived dried blood spots

Clinical Epigenetics ◽

10.1186/s13148-016-0242-1 ◽

2016 ◽

Vol 8 (1) ◽

Cited By ~ 22

Author(s):

Nicklas H. Staunstrup ◽

Anna Starnawska ◽

Mette Nyegaard ◽

Lene Christiansen ◽

Anders L. Nielsen ◽

...

Keyword(s):

Dna Methylation ◽

Dried Blood Spots ◽

Blood Spots ◽

Genome Wide ◽

Dna Methylation Profiling ◽

Methylation Profiling

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EPCO-17. METHYLATION ANALYSIS OF MATCHED PRIMARY AND RECURRENT IDHmt ASTROCYTOMA; AN UPDATE FROM THE GLIOMA LONGITUDINAL ANALYSIS NL (GLASS-NL) CONSORTIUM

Neuro-Oncology ◽

10.1093/neuonc/noab196.016 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi5-vi5

Author(s):

Wies Vallentgoed ◽

Anneke Niers ◽

Karin van Garderen ◽

Martin van den Bent ◽

Kaspar Draaisma ◽

...

Keyword(s):

Dna Methylation ◽

Surgical Resection ◽

Molecular Mechanisms ◽

Relative Proportion ◽

Low Grade ◽

High Grade ◽

Primary Tumors ◽

Genome Wide ◽

Dna Methylation Profiling ◽

Methylation Profiling

Abstract The GLASS-NL consortium, was initiated to gain insight into the molecular mechanisms underlying glioma evolution and to identify markers of progression in IDH-mutant astrocytomas. Here, we present the first results of genome-wide DNA-methylation profiling of GLASS-NL samples. 110 adult patients were identified with an IDH-mutant astrocytoma at first diagnosis. All patients underwent a surgical resection of the tumor at least twice, separated by at least 6 months (median 40.9 months (IQR: 24.0, 64.7). In 37% and 18% of the cases, patients were treated with radiotherapy or chemotherapy respectively, before surgical resection of the recurrent tumor. DNA-methylation profiling was done on 235 samples from 103 patients (102 1st, 101 2nd, 29 3rd, and 3 4th resection). Copy number variations were also extracted from these data. Methylation classes were determined according to Capper et al. Overall survival (OS) was measured from date of first surgery. Of all primary tumors, the methylation-classifier assigned 85 (87%) to the low grade subclass and 10 (10%) to the high grade subclass. The relative proportion of high grade tumors increased ~three-fold at tumor recurrence (32/101, 32%) and even further in the second recurrence (15/29, 52%). Methylation classes were prognostic, both in primary and recurrent tumors. The overall DNA-methylation levels of recurrent samples was lower than that of primary samples. This difference is explained by the increased number of high grade samples at recurrence, since near identical DNA-methylation levels were observed in samples that remained low grade. In an unsupervised analysis, DNA-methylation data derived from primary and first recurrence samples of individual patients mostly (79%) cluster together. Recurrent samples that do not cluster with their primary tumor, form a separate group with relatively low genome-wide DNA-methylation. Our data demonstrate that methylation profiling identifies a shift towards a higher grade at tumor progression coinciding with reduced genome-wide DNA-methylation levels.

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Genome-wide DNA methylation profiling shows a distinct epigenetic signature associated with lung macrophages in cystic fibrosis

Clinical Epigenetics ◽

10.1186/s13148-018-0580-2 ◽

2018 ◽

Vol 10 (1) ◽

Cited By ~ 2

Author(s):

Youdinghuan Chen ◽

David A. Armstrong ◽

Lucas A. Salas ◽

Haley F. Hazlett ◽

Amanda B. Nymon ◽

...

Keyword(s):

Cystic Fibrosis ◽

Dna Methylation ◽

Lung Macrophages ◽

Genome Wide ◽

Dna Methylation Profiling ◽

Methylation Profiling

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PATH-27. MGMT PROMOTER STATUS IN IDH1/2 MUTANT ANAPLASTIC ASTROCYTOMA PATIENTS ASSESSED BY DNA METHYLATION PROFILING AND QMS-PCR: A REPORT FROM THE EORTC BRAIN TUMOR GROUP

Neuro-Oncology ◽

10.1093/neuonc/noab196.479 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi120-vi121

Author(s):

Mircea Tesileanu ◽

Pim French ◽

Marc Sanson ◽

Alba Ariela Brandes ◽

Wolfgang Wick ◽

...

Keyword(s):

Dna Methylation ◽

Anaplastic Astrocytoma ◽

Methylation Status ◽

High Grade Glioma ◽

Phase Iii ◽

Kappa Score ◽

Adjuvant Temozolomide ◽

Tumor Group ◽

Dna Methylation Profiling ◽

Methylation Profiling

Abstract BACKGROUND Temozolomide efficacy in high-grade glioma is related to MGMTp methylation. We compared the prognostic and predictive effect of MGMTp between DNA methylation profiling (MGMT-STP27 model) and qMS-PCR in IDH1/2mt anaplastic astrocytoma patients. METHODS The 2x2 factorial design phase III CATNON trial randomized 751 adult patients with newly diagnosed 1p/19q non-codeleted anaplastic glioma to 59.4Gy radiotherapy, radiotherapy with concurrent temozolomide, radiotherapy with 12 cycles of adjuvant temozolomide, or radiotherapy with concurrent and adjuvant temozolomide. MGMTp methylation status was assessed with the MGMT-STP27 model using 850k EPIC data, and qMS-PCR. IDH1/2 mutation status was determined with next-generation sequencing. OS was measured from randomization date. RESULTS We identified 444 IDH1/2mt anaplastic astrocytoma patients. MGMTp was methylated in 365/440 patients (83.0%) with MGMT-STP27 data, and 168/361 patients (46.5%) with qMS-PCR data. The agreement between both modalities is 59.9% (Cohen’s Kappa score 0.229). At database lock, 289 patients with MGMT-STP27 data were alive and 236 patients with qMS-PCR data. The median OS of MGMTp methylated glioma patients was 9.1 yrs [95%CI 7.5-not reached] for the MGMT-STP27 model, and not reached [95%CI 9.1-not reached] for qMS-PCR. For MGMTp unmethylated glioma patients, the median OS was 6.9 yrs [95%CI 6.2-not reached] for the MGMT-STP27 model, and 6.8 yrs [95%CI 6.2-9.7] for qMS-PCR. The HR for OS based on MGMTp methylation was 0.88 [95%CI 0.58-1.31] for the MGMT-STP27 model, and 0.72 [95%CI 0.50-1.03]) for qMS-PCR. The HR for OS after radiotherapy with any temozolomide vs radiotherapy alone for the MGMT-STP27 model was 0.53 [95%CI 0.37-0.78] for MGMTp methylated, and 0.54 [95%CI 0.25-1.18] for MGMTp unmethylated glioma patients; and for MS-PCR was 0.34 [95%CI 0.19-0.61] for MGMTp methylated, and 0.53 [95%CI 0.33-0.85] for MGMTp unmethylated glioma patients. CONCLUSION MGMTp methylation, regardless of assay, was neither prognostic nor predictive for outcome to temozolomide in IDH1/2mt anaplastic astrocytoma patients.

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Genome-wide DNA methylation profiling and gut flora analysis in intestinal polyps patients

European Journal of Gastroenterology & Hepatology ◽

10.1097/meg.0000000000002181 ◽

2021 ◽

Vol Publish Ahead of Print ◽

Author(s):

Lili Liu ◽

Yanjie Chen ◽

Taotao Liu ◽

Jie Yu ◽

Lili Ma ◽

...

Keyword(s):

Dna Methylation ◽

Gut Flora ◽

Intestinal Polyps ◽

Genome Wide ◽

Dna Methylation Profiling ◽

Methylation Profiling

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Genome-wide DNA methylation profiling of human diabetic peripheral neuropathy in subjects with type 2 diabetes mellitus

Epigenetics ◽

10.1080/15592294.2019.1615352 ◽

2019 ◽

Vol 14 (8) ◽

pp. 766-779 ◽

Cited By ~ 7

Author(s):

Kai Guo ◽

Sarah Elzinga ◽

Stephanie Eid ◽

Claudia Figueroa-Romero ◽

Lucy M. Hinder ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Dna Methylation ◽

Type 2 Diabetes Mellitus ◽

Peripheral Neuropathy ◽

Diabetic Peripheral Neuropathy ◽

Genome Wide ◽

Dna Methylation Profiling ◽

Methylation Profiling

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Genome-Wide DNA Methylation Profiling in the Lotus (Nelumbo nucifera) Flower Showing its Contribution to the Stamen Petaloid

Plants ◽

10.3390/plants8050135 ◽

2019 ◽

Vol 8 (5) ◽

pp. 135 ◽

Cited By ~ 5

Author(s):

Zhongyuan Lin ◽

Meihui Liu ◽

Rebecca Njeri Damaris ◽

Tonny Maraga Nyong’a ◽

Dingding Cao ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Bisulfite Sequencing ◽

Epigenetic Modification ◽

Nelumbo Nucifera ◽

Flower Formation ◽

Relationship Analysis ◽

Genome Wide ◽

Dna Methylation Profiling ◽

Methylation Profiling

DNA methylation is a vital epigenetic modification. Methylation has a significant effect on the gene expression influencing the regulation of different physiological processes. Current studies on DNA methylation have been conducted on model plants. Lotus (Nelumbo nucifera) is a basic eudicot exhibiting variations during development, especially in flower formation. DNA methylation profiling was conducted on different flower tissues of lotuses through whole genome bisulfite sequencing (WGBS) to investigate the effects of DNA methylation on its stamen petaloid. A map of methylated cytosines at the single base pair resolution for the lotus was constructed. When the stamen was compared with the stamen petaloid, the DNA methylation exhibited a global decrease. Genome-wide relationship analysis between DNA methylation and gene expression identified 31 different methylation region (DMR)-associated genes, which might play crucial roles in floral organ formation, especially in the stamen petaloid. One out of 31 DMR-associated genes, NNU_05638 was homolog with Plant U-box 33 (PUB33). The DNA methylation status of NNU_05638 promoter was distinct in three floral organs, which was confirmed by traditional bisulfite sequencing. These results provide further insights about the regulation of stamen petaloids at the epigenetic level in lotus.

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