Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

39 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A large microRNA cluster on chromosome 19 is a transcriptional hallmark of WHO type A and AB thymomas

ABSTRACT: Thymomas are one of the most rarely diagnosed malignancies. To better understand its biology and to identify therapeutic targets, we performed next-generation RNA sequencing. The RNA was sequenced from 13 thymic malignancies and 3 normal thymus glands. Validation of microRNA expression was performed on a separate set of 35 thymic malignancies. For cell-based studies, a thymoma cell line was used. Hierarchical clustering revealed 100% concordance between gene expression clusters and WHO subtype. A substantial differentiator was a large microRNA cluster on chr19q13.42 that was significantly overexpressed in all A and AB tumors and whose expression was virtually absent in the other thymomas and normal tissues. Overexpression of this microRNA cluster activates the PI3K/AKT/mTOR pathway. Treatment of a thymoma AB cell line with a panel of PI3K/AKT/mTOR inhibitors resulted in marked reduction of cell viability. A large microRNA cluster on chr19q13.42 is a transcriptional hallmark of type A and AB thymomas. Furthermore, this cluster activates the PI3K pathway, suggesting the possible exploration of PI3K inhibitors in patients with these subtypes of tumor. This work has led to the initiation of a phase II clinical trial of PI3K inhibition in relapsed or refractory thymomas. 13 thymic malignancies and 3 Normal Thymus RNA-Sequenced in triplicate

ORGANISM(S): Homo sapiens

SUBMITTER: Milan Radovich

PROVIDER: E-GEOD-79978 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

A large microRNA cluster on chromosome 19 is a transcriptional hallmark of WHO type A and AB thymomas

Project description:Thymomas are one of the most rarely diagnosed malignancies. To better understand its biology and to identify therapeutic targets, we performed next-generation RNA sequencing. The RNA was sequenced from 13 thymic malignancies and 3 normal thymus glands. Validation of microRNA expression was performed on a separate set of 35 thymic malignancies. For cell-based studies, a thymoma cell line was used. Hierarchical clustering revealed 100% concordance between gene expression clusters and WHO subtype. A substantial differentiator was a large microRNA cluster on chr19q13.42 that was significantly overexpressed in all A and AB tumors and whose expression was virtually absent in the other thymomas and normal tissues. Overexpression of this microRNA cluster activates the PI3K/AKT/mTOR pathway. Treatment of a thymoma AB cell line with a panel of PI3K/AKT/mTOR inhibitors resulted in marked reduction of cell viability. A large microRNA cluster on chr19q13.42 is a transcriptional hallmark of type A and AB thymomas. Furthermore, this cluster activates the PI3K pathway, suggesting the possible exploration of PI3K inhibitors in patients with these subtypes of tumor. This work has led to the initiation of a phase II clinical trial of PI3K inhibition in relapsed or refractory thymomas.

2016-04-06 | GSE79978 | GEO

LINC00174 is a novel prognostic factor in Thymic Epithelial Tumors involved in cell migration and lipid metabolism

Project description:Thymoma and thymic carcinoma represent the two most characterized types of Thymic epithelial tumors (TET) which arise from epithelial cell of thymus. According to the different morphological features, lymphocytes and epithelial cells ratio and grade of malignancy, TET are divided in thymoma A, AB, B1, B2, and B3 and thymic carcinoma. We used microarrays to detail the global programme of gene expression distinguishing tumoral and normal thymic tissue, thus identifying networks of correlated mRNAs-lncRNAs.

2020-12-10 | GSE158997 | GEO

Methylation array data of thymic epithelial tumors (TC, NET, THYM)

Project description:Methylation microarray data (Illumina 850K) of 52 thymic epithelial tumors. 13 patients with thymoma A and B, 32 thymic carcinoma (TC) and 7 neuroendocrine tumors of the thymus (NET).

| EGAD00010002355 | EGA

A specific missense mutation in GTF2I occurs at high frequency in thymic epithelial tumors

Project description:Next generation sequencing of 28 thymic epithelial tumors (TETs) revealed a high frequency of GTF2I missense mutation (chr7:74146970T/A) in A thymomas, a relatively indolent subtype. The GTF2I mutation was confirmed in 82% of A and 74% of AB thymomas in a series of 274 TETs but was rare in aggressive subtypes, where recurrent mutations of known cancer genes were identified. Therefore, GTF2I mutation correlated with a better survival. GTF2I Beta and Delta isoforms were expressed in TETs and both mutant isoforms were able to stimulate cell proliferation in vitro. Thymic carcinomas presented a higher number of mutations than thymomas (average 43.5 and 18.4, respectively). Recurrent mutations of known cancer genes, including TP53, CYLD, CDKN2A, BAP1 and PBRM1 were identified in thymic carcinomas. These findings will complement the diagnostic work up of these rare tumors, and also help the development of a molecular classification, and assessment of prognosis and treatment strategies.

2014-06-24 | GSE57892 | GEO

DNA-Methylation Analysis as a Tool for Thymoma Classification

Project description:Thymomas are malignant thymic epithelial tumors that are difficult to diagnose due to their rarity and complex diagnostic criteria. They represent a morphologically heterogeneous class of tumors mainly defined by “organo-typical” architectural features and cellular composition. The diagnosis of thymoma is burdened with a high inter-observer variability and with the problem that some type-specific morphological alterations are rather a continuum than clear-cut. Methylation pattern-based classification may help to increase diagnostic precision, particularly in borderline cases.

2022-12-16 | GSE218549 | GEO

A specific missense mutation in GTF2I occurs at high frequency in thymic epithelial tumors

2014-06-24 | E-GEOD-57892 | biostudies-arrayexpress

Expression data from thymic lymphomas of Lck-MyrAkt positive mice with WT or KD mTOR expression

Project description:Lck-MyrAkt2 mice develop spontaneous thymic lymphomas at approximately 100-200 days of age, driven in part by a consitutatively-active AKT (due to myristoylation). mTOR Knock Down mice were crossed with Lck-MyrAkt postive mice to model the affects of decreasing mTOR activity on tumors with an activated PI3K/AKT/MTOR pathway. Lck-Akt/mTOR KD mice had prolonged survival compared to the Lck-Akt/mTOR WT mice. We used microarrays to compare the transcriptome in thymic lymphomas between Lck-Akt positive, mTOR WT and Lck-Akt positive, mTOR KD mice. Four thymic lymphomas from Lck-Akt/mTOR WT mice were compared to three thymic lymphomas from Lck-Akt/mTOR KD mice.

2015-09-15 | E-MTAB-3242 | biostudies-arrayexpress

A Knock-in Mouse Model of Thymoma with the GTF2I L424H Mutation

Project description:We previously identified a recurrent mutation L424H in the transcription factor GTF2I in thymic epithelial tumors. The precise role of the GTF2I mutation in these tumors is unclear. Here we describe the generation and characterization of a mouse model in which the Gtf2i L424H mutation was conditionally knocked-in in the Foxn1+ thymic epithelial cells. The Gtf2i mutation impairs development of thymic medulla and maturation of medullary thymic epithelial cells in the young mice and causes tumor formation in the thymus of the aged KI mice. To characterize the molecular features of murine thymomas, we performed digital spatial profiling with GeoMx moue whole transcriptome atlas assay with FFPE thymic tissues of 4 KI and 4 control mice.

2023-01-25 | GSE200784 | GEO

Genomic landscape and molecularly-informed therapy in thymic carcinoma and other advanced thymic epithelial tumors (H021, HIPO)

Project description:The molecular landscape of malignant thymic epithelial tumors (TET) is largely unknown. To better understand and target these clinically challenging entities, we characterize 81 patients harboring 46 thymus carcinomas (TC), 8 neuroendocrine tumors of the thymus (NET) and 27 thymomas using WGS/WES, transcriptome and methylome analysis. TC harbor different molecular alterations compared to thymoma and NET and have higher tumor mutational burden than thymomas. 14/76 TET patients show (likely) pathogenic germline alterations. Composite biomarker analysis indicates homologous repair deficiency in a subset of patients. We identify immunologically hot and cold TC. Cold TC show significantly shorter overall survival. 71/81 patients receive molecularly-informed therapy recommendations, which are applied in 28/71 cases leading to a DCR of 60% and an ORR of 24% (both n=25). 8/23 patients reach PFS ratios > 1.3, seven of them having TC.

| EGAS00001006408 | EGA

Homo sapiens

Project description:A large microRNA cluster on chromosome 19 is a transcriptional hallmark of WHO type A and AB thymomas

| PRJNA317556 | ENA