GENE-23. GENOME-WIDE DNA METHYLATION PROFILES DISTINGUISH SILENT FROM NON-SILENT ACTH ADENOMAS

Abstract BACKGROUND Corticotroph adenomas are immunopositive for adrenocorticotrophic hormone (ACTH) associated with elevated blood ACTH levels leading to Cushing disease (CD). Yet silent ACTH adenomas (SCA) immunostain for ACTH but do not cause hypercortisolism. SCA have consistently been shown to have a more aggressive postoperative course, then nonfunctioning and ACTH adenomas. Here we show that genome-wide methylation profiles can be used to distinguish ACTH adenomas from SCA. METHODS16 SCA patients and 19 CD patients that underwent transsphenoidal resection were included. Tumor size was measured by MRI. Tumor histology was proven by immunstain for ACTH and routine histopathology. Sanger sequencing was performed to analyse mutational burden within the ACTH locus (n=3). Genome-wide DNA methylation profiling was performed using a 850k Illumina EPIC array and classified by the DKFZ brain tumor classifier as well as PCA analysis using R (n=17). RESULTS Mean age was 55,4 and 46,2 for SCA and CD patients, respectively. Patients with SCA had significantly larger tumors (SCA: 12,56±3,07ccm; CD: 1,9±1,2ccm p< 0.01). Both SCA and CD tumors showed strong expression of ACTH as proven by immunohistochemistry. Sanger sequencing revealed no mutations within the ACTH gene locus in SCA. Both, SCA and CD tumors classified as ACTH adenomas by genome-wide methylation profiling. Further PCA of DNA methylation profiles allowed subtype tumor classification into SCA and CD adenomas. CONCLUSION SCA show a strong expression of ACTH without causing hypercortisolism. The reason for this is not yet known. Our data suggest that SCA do not harbor specific mutations within the ACTH gene locus. However genome wide methylation profiles allows subgrouping of SCA and CD adenomas.

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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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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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