Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Integration of miRNA, mRNA and methylation profiling reveals genes aberrantly regulated associated to RETM918T mutation in Medullary Thyroid Carcinoma [methylation component]

ABSTRACT: Medullary thyroid carcinoma (MTC) accounts for 1-2% of thyroid malignancies. It is a disease of few genetic drivers, and the etiology specifically associated with each mutation remains unknown. Here, we investigated the role of aberrant DNA methylation in the MTC development. We performed genome-wide DNA methylation profiling assessing >27,000 CpGs in the largest MTC series reported to date, comprising 48 molecularly characterized tumors. We observed significant differences between the methylation patterns among the samples bearing the RETM918T, RETC634 mutation and “wild-type” (WT) tumors, but not those RAS-related. In detail, the RETM918T –related tumors had a larger number of hypomethylation events when compared to RETC634 – positive and WT ones. Moreover, through the integration of methylation with mRNA and miRNA expression data of the same tumors, we identified genes whose expression is negatively correlated with the methylation status of their promoters. For PLCB2, DKK4, MMP20 as well as miR-10a, -30a and -200c, the impact of promoter methylation levels on expression of these genes in MZ-CRC-1 and TT cell lines was assessed. Finally, the aberrant methylation validation of three of the genes in an independent set of 25 MTCs by bisulfite pyrosequencing suggests their role as MTC methylation markers.

ORGANISM(S): Homo sapiens

PROVIDER: GSE72729 | GEO | 2016/12/31

SECONDARY ACCESSION(S): PRJNA294777

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Integration of miRNA, mRNA and methylation profiling reveals genes aberrantly regulated associated to RETM918T mutation in Medullary Thyroid Carcinoma [miRNA component]

Project description:Medullary thyroid carcinoma (MTC) accounts for 1-2% of thyroid malignancies. It is a disease of few genetic drivers, and the etiology specifically associated with each mutation remains unknown. Here, we investigated the role of aberrant DNA methylation in the MTC development. We performed genome-wide DNA methylation profiling assessing >27,000 CpGs in the largest MTC series reported to date, comprising 48 molecularly characterized tumors. We observed significant differences between the methylation patterns among the samples bearing the RETM918T, RETC634 mutation and “wild-type” (WT) tumors, but not those RAS-related. In detail, the RETM918T –related tumors had a larger number of hypomethylation events when compared to RETC634 – positive and WT ones. Moreover, through the integration of methylation with mRNA and miRNA expression data of the same tumors, we identified genes whose expression is negatively correlated with the methylation status of their promoters. For PLCB2, DKK4, MMP20 as well as miR-10a, -30a and -200c, the impact of promoter methylation levels on expression of these genes in MZ-CRC-1 and TT cell lines was assessed. Finally, the aberrant methylation validation of three of the genes in an independent set of 25 MTCs by bisulfite pyrosequencing suggests their role as MTC methylation markers.

2016-12-31 | GSE72728 | GEO

Characterization of neuroendocrine tumors in heterozygous mutant MENX rats: a novel model of invasive medullary thyroid carcinoma [thyroid]

Project description:CDKN1B (p27) was formally established as a tumor suppressor gene (tsg) following the identification of inactivating germline mutations in rats (MENX syndrome) and patients (MEN4 syndrome) developing multiple neuroendocrine tumors (NETs). MENX-affected rats are homozygous for the predisposing p27 mutation, suggesting a canonical tsg function. In contrast, mice heterozygous for a defective Cdkn1b allele are already predisposed to tumor formation (haploinsufficiency). We here report that heterozygous mutant rats (p27+/mut) develop the same NETs seen in the homozygous (p27mut/mut) animals but with slower progression. In the tumors of p27+/mut rats, the wild-type allele is neither lost nor silenced, implying that p27 is haploinsufficient for tumor suppression also in this model. Transcriptome profiling of rat NETs having different p27 dosages revealed a tissue-specific, dose-dependent effect of p27 on gene expression. In p27+/mut rats, thyroid neoplasms progress to invasive and metastatic medullary thyroid carcinomas (MTCs) accompanied by increased calcitonin levels, as in humans. Comparison of expression signatures of late-stage versus early-stage MTCs from p27+/mut rats identified genes potentially involved in tumor aggressiveness. The expression of a subset of these genes was evaluated in human MTCs, and found associated with aggressive RET-M918T-positive tumors. Altogether, p27 haploinsufficiency in MENX rats uncovered a novel, representative model of invasive/metastatic MTC, exploitable for translational studies of this aggressive and often incurable cancer.

2017-11-15 | GSE98546 | GEO

Transcriptional Targeting Of Oncogene Addiction In Medullary Thyroid Cancer [RNA-Seq]

Project description:Metastatic medullary thyroid cancer (MTC) is a currently incurable disease. FDA approved therapies that target RET, a commonly mutated receptor tyrosine kinase in MTC, and other receptor tyrosine kinases, do not result in complete responses and acquired resistance is universal due to “gatekeeper” mutation in Ret or overactivation of alternative signaling pathways. Based on data from human MTCs and a number of murine models, the CDK/RB cell cycle pathway is a potential alternative target for MTC. The objective of this study was to determine if CDKs represent therapeutic targets for MTC and to define mechanisms of activity. We demonstrate that targeting the CDK/RB pathway with Palbociclib (CDK4/6 inhibitor) is not cytotoxic to MTC cells but that Dinaciclib (CDK1/2/5/9 inhibitor) remarkably reduced cell viability and proliferation at low doses in two MTC cell lines accompanied by loss of CDK9 and RET protein and mRNA levels. In human tumors, CDK9 protein was highly expressed and array CGH demonstrated copy number gain in 11/30 analyzed tumors. RNA sequencing demonstrated that RNA polymerase II-dependent transcription was markedly reduced by Dinaciclib, consistent with transcriptional mode of action. Subsequent studies using the CDK7 inhibitor, THZ1, demonstrated high potency vs. the MTC cell lines and marked loss of RET mRNA and protein. In silico analysis, and CHIP-Sequencing using H3K27Ac antibody confirmed that RET is associated with a super-enhancer in RET-mutated MTC cells. In summary, this study reveals a novel mechanism of RET transcription regulation that represents a potentially translatable finding for new therapeutic approaches for RET-mutated MTC.

2018-12-25 | GSE114069 | GEO

Transcriptional Targeting Of Oncogene Addiction In Medullary Thyroid Cancer [ChIP-Seq]

2018-12-25 | GSE114068 | GEO

DIFFERENTIAL GENE EXPRESSION OF MEDULLARY THYROID CARCINOMA REVEALS SPECIFIC MARKERS ASSOCIATED WITH GENETIC CONDITIONS.

Project description:Transcriptional analysis of 49 primary medullary thyroid carcinoma tumors. Comparisons MTCM918T vs MTC634 and MTCM918T vs MTCWT. 49 (52 hybridized tumors with 3 replicates) primary Medullary Thyroid Carcinoma (MTC) cases were hybridized onto a cDNA microarray in order to identify the unique markers for specific genetic classes of MTC.

2013-11-26 | E-GEOD-32662 | biostudies-arrayexpress

Magnetic-Targeted Doxorubicin in Treating Patients With Cancer Metastatic to the Liver

Project description:MTC-DOX is Doxorubicin or DOX, a chemotherapy drug, that is adsorbed, or made to "stick", to magnetic beads (MTCs). MTCs are tiny, microscopic particles of iron and carbon. When DOX is added to MTCs, DOX attaches to the carbon part of the MTCs. MTC-DOX is directed to and deposited in the area of a tumor, where it is thought that it then "leaks" through the blood vessel walls. Once in the surrounding tissues, it is thought that Doxorubicin becomes "free from" the magnetic beads and will then be able to act against the tumor cells. The iron component of the particle has magnetic properties, making it possible to direct MTC-DOX to specific tumor sites in the liver by placing a magnet on the body surface. It is hoped that MTC-DOX used with the magnet may target the chemotherapy drug directly to liver tumors and provide a treatment to patients with cancers that have spread to the liver.

| 2007949 | ecrin-mdr-crc

Quantitative proteomics analysis of medullary thyroid carcinoma

Project description:Medullary thyroid cancer (MTC) accounts for less than 5% of all thyroid cancers, and it is a rare neuroendocrine tumor which derives from calcitonin-secreting thyroid C cells.Given the underlying mechanism involved in MTC remain unclear, the development and the specific pathways of MTC require further investigation.here we employed the application of TMT6plex-based LC-MS/MS to identify and analyze the novel differentially-expressed proteins(DEPs) from MTC patients, To our best knowledge, it is the first study to comprehensively investigate the molecular mechanisms of MTC by proteomics technology from Chinese MTC patients’ tissues, and these DEPs identified in our study will provide a better understanding of the underlying pathophysiology of MTC, as well as may provide potential therapeutic targets for patients with MTC.

2020-05-26 | PXD005898 | Pride

Gene profile of human medullary thyroid cancer

Project description:We report gene expression profiling in a series of 17 human medullary thyroid cancer (MTC) tissues, including 8 primary tumors and 9 patient paired neck nodes metastases, in comparison with 3 non-neoplastic thyroid tissues. For the same series we have previously reported miRNA expression profiles (GSE97070 series).

2022-04-27 | GSE196264 | GEO

The yeast RNA methylation complex consists of conserved yet reconfigured components with m6A-dependent and independent roles

Project description:N6-methyladenosine (m6A), the most abundant mRNA modification, is deposited in mammals/drosophila/plants by m6A methyltransferase complexes (MTC) comprising a catalytic subunit and at least five additional proteins. The yeast MTC is critical for meiosis but was known to comprise three proteins, of which two were conserved in mammals. We uncover three novel MTC components (Kar4/Ygl036w-Vir1/Dyn2). All MTC subunits, except for Dyn2, are essential for m6A deposition and have corresponding mammalian orthologs. Nonetheless, the yeast MTC is arranged differently from its mammalian counterpart. The yeast MTC features a mostly mutually stabilizing core comprising Ime4/Mum2/Vir1 and the mRNA binding component Kar4, and an auxiliary hub comprising Slz1/Dyn2. The MTC core subunits when in a complex have both m6A-dependent and m6A-independent functions in meiosis. Kar4 also has a mechanistically separate function from the MTC during mating. Our findings expand the relevance of yeast as a model for unravelling m6A-dependent and independent functions of MTCs.

2023-07-19 | GSE224637 | GEO

Phase 1/2 Study of the Highly-selective RET Inhibitor, Pralsetinib (BLU-667), in Participants With Thyroid Cancer, Non-Small Cell Lung Cancer, and Other Advanced Solid Tumors

Project description:This is a Phase 1/2, open-label, first-in-human (FIH) study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antineoplastic activity of pralsetinib (BLU-667) administered orally in participants with medullary thyroid cancer (MTC), RET-altered NSCLC and other RET-altered solid tumors.

| 2235487 | ecrin-mdr-crc

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data