Genetic and methylation profiles distinguish benign, malignant and spitzoid melanocytic tumors
Ontology highlight
ABSTRACT:
PROVIDER: EGAS00001006205 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:Methylation profiles of benign and malignant bone tumorus
| PRJNA489284 | ENA
Project description:Spitzoid neoplasms are a challenging group of cutaneous melanocytic proliferations that occur in children or adolescents but can also arise in the elderly. They are characterized by epithelioid and/ or spindle-shaped melanocytes with a stromal background of variable amounts of lymphocytes, blood vessels and sclerosis. According to the WHO 2018 classification, Spitzoid melanocytic lesions are classified as benign Spitz nevi (SN), atypical Spitz tumors (AST) or malignant Spitz tumors (MST). The intermediate AST category represents a diagnostically challenging group since on purely histopathological grounds, their benign or malignant character remains unpredictable. This results in uncertainties in patient management and prognosis. The molecular properties of Spitzoid lesions, especially their transcriptomic landscape, remain poorly understood and genomic alterations in melanoma-associated oncogenes are typically absent. The aim of this study was to characterize the transcriptome of Spitzoid melanocytic neoplasms with digital mRNA expression profiling. Formalin-fixed-paraffin-embedded samples (including 27 SN, 10 AST and 14 MST) were analyzed using the RNA NanoString nCounter PanCancer Pathways Gene Expression panel. The number of significantly differentially expressed genes in SN vs. MST, SN vs. AST and AST vs. MST was 68, 167 and 18, respectively. Gene set enrichment analysis revealed an upregulation of pathways related to epithelial mesenchymal transition, immunomodulatory-, angiogenesis- as well as myogenesis associated processes in AST and MST. In addition, a specific gene expression signature of SN vs. MST was discovered based on the top-ranked six most informative gene expression markers: NRAS, NF1, BMP2, EIF2B4, IFNA17 and FZD9. The AST samples showed intermediate levels of the identified signature. This implies that the identified gene expression signature can potentially be used to distinguish high-grade from low-grade AST. This combined histopathological and transcriptomic methodology is promising for diagnostics of Spitzoid neoplasms and patient management in dermatological oncology in the future.
2019-10-25 | GSE139314 | GEO
Project description:Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine, usually benign tumors. Currently, for these neoplasms the only reliable criterion of malignancy is the presence of metastases. The aim of the present study was to identify molecular markers that can distinguish malignant from benign PPGL. An mRNA expression array was performed on 40 benign and 11 malignant PPGL. Genes showing a significantly different expression between benign and malignant PPGL with a ratio ? 4 were selected. Differentially expressed genes were confirmed by qRT-PCR and subsequently tested in an independent validation series (4 benign and 4 malignant) by qRT-PCR. Finally, immunohistochemistry was performed for the validated genes on Tissue Micro Arrays, which included 100 PPGL (87 benign and 13 malignant). Ten genes, which were significantly differentially expressed between benign and malignant tumors (False Discovery Rates <0.05), were selected from the mRNA expression array data. Differential expression of Interleukin 13 Receptor Alpha 2 and Contactin 4 was confirmed (p<0.05) and validated by qRT-PCR. However, at the protein level, only Contactin 4 appeared to be significantly overexpressed in malignant tumors (58% in malignant versus 17% in benign; p<0.05). No difference in the immunohistochemical staining for Interleukin 13 Receptor Alpha 2 was observed between benign and malignant PPGL. Contactin 4 expression appears to be associated with malignancy in pheochromocytomas and paragangliomas, and may be predictive of malignant behavior.
2015-03-20 | GSE67066 | GEO
Project description:We have compared the microsomal protein fractions from benign and malignant adrenocortical tumors. Protein extracts were trypsinized, peptides separated by HiRIEF (high resolution isoelectric focusing) and analysed by LC-MS.
2014-02-11 | PXD000604 | Pride
Project description:Serous borderline tumours (SBOT) are a challenging group of ovarian tumours positioned between benign and malignant disease. We have profiled the DNA methylomes of 12 low grade serous carcinoma (LGSC), 19 SBOT and 16 benign serous tumours (BST) across 27,578 CpG sites to further characterise the epigenomic relationship between these subtypes of ovarian tumours. Unsupervised hierarchical clustering of DNA methylation levels showed that LGSC differ distinctly from BST, however, not from SBOT. Gene ontology analysis of genes showing differential methylation at linked CpG sites between LGSC and BST revealed significant enrichment of gene groups associated with cell adhesion, cell-cell signalling and the extracellular region consistent with a more invasive phenotype of LGSC as compared to BST. Consensus clustering highlighted differences between SBOT methylomes and returned subgroups with malignant-like or benign-like methylation profiles. Furthermore, a two loci DNA methylation signature can distinguish between these SBOT subgroups with benign-like and malignant-like methylation characteristics. Our findings indicate striking similarities between SBOT and LGSC methylomes which supports a common origin and the view that LGSC may arise from SBOT. A subgroup of SBOT can be classified into tumours with a benign-like or a malignant-like methylation profile which may help in identifying tumours more likely to progress into LGSC.
2012-12-31 | GSE40105 | GEO
Project description:Perturbations in microRNA (miRNA) expression profiles has been reported for cutaneous malignant melanoma (CMM). With regards to a rapidly growing number of newly discovered miRNA sequences, the availability of up-to-date miRNA expression profiles for primary cutaneous malignant melanoma (PCMM), cutaneous malignant melanoma metastases (CMMM) and benign melanocytic naevi (BMN) is limited. Patients with PCMM (n=9), CMMM (n=4) and BMN (n=8) were included in the study. Specimens were obtained during surgery from the center of the tumors (lesional). An exploratory microarray analysis was performed by miRNA expression profiling based on miRBase V.16. Additionally, the expression levels of selected miRNA candidates were confirmed by TaqMan real-time quantitative polymerase chain reaction (RT-PCR). New miRNA candidates previously not described to be associated with CMM were found to be potentially dysregulated in CMM.
2012-11-02 | GSE34460 | GEO
Project description:Serous borderline tumours (SBOT) are a challenging group of ovarian tumours positioned between benign and malignant disease. We have profiled the DNA methylomes of 12 low grade serous carcinoma (LGSC), 19 SBOT and 16 benign serous tumours (BST) across 27,578 CpG sites to further characterise the epigenomic relationship between these subtypes of ovarian tumours. Unsupervised hierarchical clustering of DNA methylation levels showed that LGSC differ distinctly from BST, however, not from SBOT. Gene ontology analysis of genes showing differential methylation at linked CpG sites between LGSC and BST revealed significant enrichment of gene groups associated with cell adhesion, cell-cell signalling and the extracellular region consistent with a more invasive phenotype of LGSC as compared to BST. Consensus clustering highlighted differences between SBOT methylomes and returned subgroups with malignant-like or benign-like methylation profiles. Furthermore, a two loci DNA methylation signature can distinguish between these SBOT subgroups with benign-like and malignant-like methylation characteristics. Our findings indicate striking similarities between SBOT and LGSC methylomes which supports a common origin and the view that LGSC may arise from SBOT. A subgroup of SBOT can be classified into tumours with a benign-like or a malignant-like methylation profile which may help in identifying tumours more likely to progress into LGSC. Array-based methylation profiling was performed using the Infinium HumanMethylation27 BeadChip in 12 low grade serous carcinoma, 19 serous borderline tumours and 16 benign serous tumours. The reproducibility of the Infinium HumanMethylation27 BeadChips was evaluated using four biological replicates of the high grade serous ovarian cancer cell line PEO1. Differential methylation cutoff was estimated from four biological replicates by bootstrap resampling and set at Δβ ≥ 0.25 corresponding to a FDR ≤ 0.09.
2012-12-31 | E-GEOD-40105 | biostudies-arrayexpress
Project description:Comparison of expression profiling of pancreas from patients suffering cancer (malignant tumors) and controls (benign tumors).
2009-03-25 | E-MEXP-1914 | biostudies-arrayexpress
Project description:The Homeobox (HOX) family of genes encodes transcription factors involved in basic developmental processes, most notably during embryogenesis. A possible HOX gene link between development and oncogenesis has recently been described. Dysregulation of HOX genes may be an early event in malignant transformation likely to induce antibody response and thus provide a potential marker for early diagnosis of cancer. Ovarian cancer is characterized by poor early detection and serves as an excellent model system to develop potential markers for early diagnosis. In this study we begin to characterize HOX gene expression in malignant tumors of the ovary and analyze the potential role of HOX genes as biomarkers for early detection of ovarian cancer. Microarray analysis of mRNA from human ovarian tissues was performed on 65 samples of normal, benign, borderline malignant and malignant ovarian tissue. These samples were analyzed using the Affymetrix Human Genome Focus GeneChip (HG-Focus) microarray to distinguish the differential pattern of mRNA expression between the four types of samples. Real-time reverse transcription PCR was utilized to confirm up-regulation of HOX genes as determined by microarray analysis. Our results demonstrate multiple HOX genes to be up-regulated in ovarian cancer. We have shown stepped increase in HOX expression comparing normal, benign neoplastic, and malignant human ovarian tissue samples. This suggests dysregulation of HOX genes may be an early event in malignant transformation and warrants additional studies to validate HOX gene products as potential markers for early detection of ovarian cancer. Experiment Overall Design: 67 samples were analyzed. 4 groupings based on pathology (normal, benign, borderline malignant, malignant). An average of normal samples was used as controls. Cell lines were used as ovarian cancer control samples.
2008-10-17 | E-GEOD-4122 | biostudies-arrayexpress
Project description:This study found evidence of early metabolic alterations that can distinguish SPNs from healthy controls, but not for benign and malignant SPNs (lung cancer in stage I), highlighting that malignant SPNs less than 3 cm in diameter are most likely lung cancer at some early stage that does not affect blood circulation. Benign SPNs seldom require excessive treatment, and the strategy to detecting and managing malignant SPNs is to perform periodic radiographic examinations and, if operable, bring patients to surgery as quickly as feasible to prevent cancer cells from entering the circulation.
2021-09-11 | ST001937 | MetabolomicsWorkbench