Genomic analysis of melanocytic neoplasms
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ABSTRACT:
PROVIDER: PRJNA434348 | ENA |
REPOSITORIES: ENA
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Project description:Genomic analysis of melanocytic neoplasms
| PRJNA434347 | 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:In our clinical practice, we perform genome-wide high-resolution SNP-array analysis as an adjunct to the histopathologic diagnosis for diagnostically challenging melanocytic tumors. The concept of using array-based DNA copy number analysis to screen for gene fusions associated with unbalanced genomic aberrations flanking the fusion points was applied in the diagnostic setting, and intragenic copy number changes involving common receptor kinase genes are typically further analyzed and, if necessary, studied by alternative methods. Here we present the discovery of recurrent NTRK3 gene rearrangements in childhood melanocytic neoplasms based on genome-wide high-resolution SNP-array analysis.
2017-02-01 | GSE90644 | GEO
Project description:A Digital mRNA Expression Signature to Classify Challenging Spitzoid Melanocytic Neoplasms
| PRJNA579272 | ENA
Project description:We analyzed the copy number profiles of clinical samples of diagnostically difficult melanocytic tumors. Of 1202 cases, 22 cases demonstrated relative gain of the 5' portion of NTRK3. We further performed DNA or RNA sequencing on 12 of these cases and identified ETV6-NTRK3, MYO5A-NTRK3 and MYH9-NTRK3 fusions in the 8 cases in this cohort. Analysis of genomic copy number of melanocytic tumors versus commericial pooled normal control.
2017-05-18 | GSE81625 | GEO
Project description:Transcriptome analysis of human hairy melanocytic nevi
| PRJNA445288 | ENA
Project description:The newest WHO classification suggests eliminating cases with BRAF and NRAS mutations from the categories of Spitz tumors (ST) and Spitz melanoma (SM). We aimed to better characterize the genomics of Spitz neoplasms and assess whether integrating genomic data with morphologic diagnosis improves classification and prognostication. We performed DNA and RNA sequencing on 80 STs, 26 SMs, and 22 melanomas with Spitzoid features (MSF). NGS data was used to reclassify tumors by moving BRAF/NRAS-mutated cases to MSF. Eighty-one percent of STs harbored kinase fusions/truncations. Of SMs, 77% had fusions/truncations, 8 involving MAP3K8. Novel fusions identified were MYO5A-FGFR1, MYO5A-ERBB4, and PRKDC-CTNNB1. The majority of MSFs (84%) had BRAF, NRAS, or NF1 mutations, and 62% had TERT promoter mutations. Only after reclassification, the following was observed: 1) mRNA expression showed distinct clustering of MSF; 2) 6/7 cases with recurrence and all distant metastases were MSFs; 3) RFS was worse in MSF than ST and SM groups (p=0.0073); 4) classification incorporating genomic data was highly predictive of recurrence (OR 13.20, p=0.0197). The majority of STs and SMs have kinase fusions as primary initiating genomic events. Eliminating BRAF/NRAS-mutated neoplasms from these categories results in improved classification and prognostication of melanocytic neoplasms with Spitzoid cytomorphology.
2020-08-27 | GSE142442 | GEO
Project description:To predict the progression risk of non-invasive gland-forming gastric neoplasms to invasive carcinoma, we assessed lineage continuity or discontinuity between the non-invasive and invasive neoplasms by applying hierarchical clustering analysis to the gene copy-number profiles of individual tumours. array-based Comparative Genomic Hybridization. Samples are including of 7 tumours of Vienna category 3, 12 tumours of Vienna category 4, 8 intramucosal cancers (Vienna category 5), 16 intramucosal lesions and 16 invasive parts (Vienna category 5); 40 reference for control, 19 control replicates
2014-08-06 | E-GEOD-60116 | biostudies-arrayexpress
Project description:To predict the progression risk of non-invasive gland-forming gastric neoplasms to invasive carcinoma, we assessed lineage continuity or discontinuity between the non-invasive and invasive neoplasms by applying hierarchical clustering analysis to the gene copy-number profiles of individual tumours.
2014-08-06 | GSE60116 | GEO
Project description:The newest WHO classification suggests eliminating cases with BRAF and NRAS mutations from the categories of Spitz tumors (ST) and Spitz melanoma (SM). We aimed to better characterize the genomics of Spitz neoplasms and assess whether integrating genomic data with morphologic diagnosis improves classification and prognostication. We performed DNA and RNA sequencing on 80 STs, 26 SMs, and 22 melanomas with Spitzoid features (MSF). NGS data was used to reclassify tumors by moving BRAF/NRAS-mutated cases to MSF. Eighty-one percent of STs harbored kinase fusions/truncations. Of SMs, 77% had fusions/truncations, 8 involving MAP3K8. Novel fusions identified were MYO5A-FGFR1, MYO5A-ERBB4, and PRKDC-CTNNB1. The majority of MSFs (84%) had BRAF, NRAS, or NF1 mutations, and 62% had TERT promoter mutations. Only after reclassification, the following was observed: 1) mRNA expression showed distinct clustering of MSF; 2) 6/7 cases with recurrence and all distant metastases were MSFs; 3) RFS was worse in MSF than ST and SM groups (p=0.0073); 4) classification incorporating genomic data was highly predictive of recurrence (OR 13.20, p=0.0197). The majority of STs and SMs have kinase fusions as primary initiating genomic events. Eliminating BRAF/NRAS-mutated neoplasms from these categories results in improved classification and prognostication of melanocytic neoplasms with Spitzoid cytomorphology.
2020-02-26 | GSE142441 | GEO