Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Targeted sequencing CYLD cutaneous syndrome

ABSTRACT: Patients with CYLD cutaneous syndrome (CCS; syn. Brooke-Spiegler syndrome) carry germline mutations in the tumor suppressor CYLD and develop multiple skin tumors with diverse histophenotypes. We comprehensively profiled the genomic landscape of 42 benign and malignant tumors across 13 individuals from four multigenerational families. Novel recurrent mutations were found in epigenetic modifiers DNMT3A and BCOR in 29% of benign tumors. Multi-level and microdissected sampling strikingly reveal that many clones with different DNMT3A mutations exist in these benign tumors, suggesting that intra-tumor heterogeneity is common. Integrated genomic, methylation and transcriptomic profiling in selected tumours suggest that isoform specific DNMT3A2 mutations are associated with dysregulated Wnt/ß-catenin pathway signaling. Phylogenetic and mutational signature analyses confirm cylindroma pulmonary metastases from primary skin tumours. These findings add novel dimensions to existing paradigms of cutaneous tumorigenesis and metastasis.

PROVIDER: EGAS00001003840 | EGA |

REPOSITORIES: EGA

ACCESS DATA

Json Xml

Similar Datasets

Methylation CYLD cutaneous syndrome

Project description:Patients with CYLD cutaneous syndrome (CCS; syn. Brooke-Spiegler syndrome) carry germline mutations in the tumor suppressor CYLD and develop multiple skin tumors with diverse histophenotypes. We comprehensively profiled the genomic landscape of 42 benign and malignant tumors across 13 individuals from four multigenerational families. Novel recurrent mutations were found in epigenetic modifiers DNMT3A and BCOR in 29% of benign tumors. Multi-level and microdissected sampling strikingly reveal that many clones with different DNMT3A mutations exist in these benign tumors, suggesting that intra-tumor heterogeneity is common. Integrated genomic, methylation and transcriptomic profiling in selected tumours suggest that isoform specific DNMT3A2 mutations are associated with dysregulated Wnt/ß-catenin pathway signaling. Phylogenetic and mutational signature analyses confirm cylindroma pulmonary metastases from primary skin tumours. These findings add novel dimensions to existing paradigms of cutaneous tumorigenesis and metastasis.

| EGAS00001003800 | EGA

RNA sequencing CYLD cutaneous syndrome

| EGAS00001003841 | EGA

Whole exome sequencing CYLD cutaneous syndrome

| EGAS00001003839 | EGA

Transcription profiling by array of human CYLD defective skin tumours and perilesional skin

Project description:Comparison of transcriptomes between CYLD defective skin tumours and perilesional skin

2011-08-16 | E-MTAB-352 | biostudies-arrayexpress

Cyld CGH

Project description:In order to identify the function of the tumor suppressor CYLD in liver, we generate a liver specific disruption of this gene in mouse (liver specific CYLD KO mice). In our analysis it was revealed that these mice initially develop fibrosis and finally they develop spontaneous liver cancer after 1 year of age. We performed CGH analysis in 8 different tumor foci from the tumor livers of 4 different CYLD liver specific KO animals, in comparison to wild type reference liver DNA. From every tumor liver, two cancer foci was microdissected. Cancer foci samples with IDs: DS-071_01 and DS-071_02 are from liver specific CYLD KO animal #1, DS-071_03 and DS-071_04 are from liver specific CYLD KO animal #2, DS-071_05 and DS-071_06 are from liver specific CYLD KO animal #3, DS-071_07 and DS-071_08 are from liver specific CYLD KO animal #4. Liver genomic DNA from cancer samples and from a reference wild type liver was extracted (Qiagen) and CGH analysis was performed to determine DNA copy number changes (IMGM Laboratories, Germany). This analysis revealed a large number of amplifications and deletions ranging from 0,62Mb to 14,8Mb in all chromosomes.

2011-12-21 | E-MTAB-905 | biostudies-arrayexpress

3641bbb4-991f-45f9-a762-c57838a4f08c - samples

Project description:This dataset contains genomic and transcriptomic profiling of skin samples (74) from patients with CYLD cutaneous syndrome

| EGAD00001005305 | EGA

Gene expression profiling of SAS cell line transfected with siRNA targeting CYLD

Project description:Oral squamous cell carcinoma (OSCC) has a very poor prognosis due to its highly invasive nature, and 5-year survival rate has not changed apparently for the past 30 years. Although cylindromatosis (CYLD) is thought as a potent tumor suppressor, its biological and clinical significances in OSCC are largely unknown. The aim of this study was to clarify roles of CYLD in OSCC progression. Our immunohistochemical analyses revealed that CYLD expression was significantly reduced at invasive lesions in OSCC tissues whereas it was conserved in normal epithelium and carcinoma in situ. Accordingly, downregulation of CYLD by siRNA led to an acquisition of mesenchymal state and increased migratory and invasive activities in OSCC cells and HaCaT keratinocytes. Interestingly, CYLD knockdown promoted TGF-beta signaling by inducing TGF-beta receptor I (ALK5) stabilization in a cell autonomous fashion. In addition, the response to exogenous TGF-beta stimulation was enhanced by CYLD downregulation. The invasive phenotype induced by CYLD knockdown were completely blocked by an ALK5 inhibitor. Furthermore, lower CYLD expression was significantly associated with deep invasion, poor overall survival, and increased Smad3 phosphorylation which is an indicator of TGF-beta signaling activation in invasive OSCC. These findings suggest that downregulation of CYLD promotes invasion with mesenchymal transition via ALK5 stabilization in OSCC cells.

2017-06-29 | GSE100589 | GEO

Cylindromas sun protected and exposed

Project description:The project aims to look at mutational signatures in a rare inherited skin tumour syndrome called CYLD cutaneous syndrome. These patients develop multiple skin tumours that are seen at sun exposed and sun protected sites. We plan to carry out WGS on carefully curated tumours from such patients. We then plan to analyse this data for mutational signatures, comparing this between sun exposed and sun protected sites.

| EGAS00001002521 | EGA

EGAS00001002521-sc-20190121 - samples

Project description:Patients with germline mutations in CYLD can develop hundreds of benign skin tumours called cylindromas. The development of multiple tumours within a single patient at sun-protected and sun-exposed sites, varying tumour histological patterns and grades of malignancy allow for the testing of several genetic hypothesis in relation to cutaneous carcinogenesis. By adopting the unprecedented approach of whole genome sequencing of multiple benign skin tumours within individuals in multigenerational families, we set out to study the impact of mutational diversity on models such as multistep carcinogenesis as well as non-sequential carcinogenesis. Using non-negative matrix factorisation (NMF) to discover mutational signatures, we found distinct mutational signatures in identical benign tumours (N=2 patients; n=11 tumours) at sun exposed and sun protected skin tumours within a mother and her daughter. We found recurrent mutations in epigenetic modifying genes in CCS tumours which are known to have an oncogenic dependency on Wnt signalling. We also demonstrate that cutaneous tumours that metastasize to the lung carry a a UV signature, supporting the origin from the skin. Distinct malignant tumours, such as BCC and malignant spiradenocarcinoma carried unique driver mutations. These findings add new dimensions to the existing paradigms of UV-induced skin cancer and highlight the utility of studying rare disease to gain novel insights into genetic mechanisms of tumour formation.

| EGAD00001004573 | EGA

EGF-dependent ubiquitinome, phosphorylation and interactome analysis in control and CYLD-deficient cells

Project description:Cylindromatosis tumor suppressor protein (CYLD) is deubiquitinase, best known as an essential negative regulator of the NFkB pathway. Previous studies have suggested an involvement of CYLD in epidermal growth factor (EGF)-dependent signal transduction as well, as it was found enriched within the tyrosine-phosphorylated complexes in cells stimulated with the growth factor. EGF receptor (EGFR) signaling participates in central cellular processes and its tight regulation, partly through ubiquitination cascades, is decisive for a balanced cellular homeostasis. Here, using a combination of mass spectrometry-based quantitative proteomic approaches with biochemical and immunofluorescence strategies, we demonstrate the involvement of CYLD in the regulation of the ubiquitination events triggered by EGF. Our data show that CYLD regulates the magnitude of ubiquitination of several major effectors of the EGFR pathway by assisting the recruitment of the ubiquitin ligase Cbl-b to the activated EGFR complex. Notably, the deficiency of CYLD impairs the interaction of EGFR with Cbl-b, which leads to a reduced ubiquitination of the receptor followed by its decreased degradation. This represents a previously uncharacterized strategy exerted by this deubiquitinase and tumors pressor for the negative regulation of a tumorigenic signaling pathway.

2017-06-05 | PXD006390 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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