Molecular Profiling of Spitz Nevi (SN) in Relation to Nevocellular Nevi (NCN)
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PROVIDER: PRJNA434073 | ENA |
REPOSITORIES: ENA
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Project description:The molecular properties of benign melanocytic lesions are poorly understood. Only few studies have been performed on specific nevi subtypes, including common nevocellular nevi (NCN) or Spitz nevi (SN). Genomic alterations in melanoma-associated oncogenes are typically absent in SN. In the present study, mRNA expression of 25 SN and 15 NCN were analyzed. Molecular profiling was done using the RNA NanoString nCounter Gene Expression Platform (No. of genes = 770). Marker discovery was performed with a training set consisting of 7 SN and 7 NCN samples from the same patients, and validation was performed using a second set consisting of 18 SN and 8 NCN samples. Using the training set, 197 differentially expressed genes were identified in SN versus NCN. Of these, 74 genes validated in the validation set (FDR Q value ≤ 0.13). In addition, using Random Forest and LASSO feature selection a molecular signature of SN versus NCN was identified including 15 top-ranked genes. Gene set analysis showed upregulation of gene pathways with increased expression of transcripts related to immunomodulatory, inflammatory and extracellular matrix interactions as well as angiogenesis associated processes in SN. Although the molecular characteristics of malignant melanoma have been studied in detail, the molecular properties of benign melanocytic lesions such as common nevocellular nevi (NCN) and Spitz nevi (SN) remain poorly understood. This limited knowledge hinders a better understanding of atypical and malignant transformation of melanocytes. The present study identified a distinct molecular expression profile in SN compared to NCN, even when lesions were obtained from the same patients. These findings strongly indicate that SN represent a distinct group of melanocytic neoplasms and evolve differentially and not sequentially from NCN.
2018-02-15 | GSE110589 | GEO
Project description:Distinguishing between Spitz nevus and melanoma presents a challenging task for clinicians and pathologists. Most of these lesions are submitted entirely in formalin for histologic analysis by conventional hematoxylin and eosin-stained sections, and fresh-frozen material for ancillary studies is rarely collected. Molecular techniques, such as comparative genomic hybridization (CGH), can detect chromosomal alterations in tumor DNA that differ between these 2 lesions. This study investigated the ability of high-resolution array-based CGH to serve as a diagnostic test in distinguishing Spitz nevus and melanoma using DNA isolated from formalin-fixed and paraffin-embedded samples. Two of 3 Spitz nevi exhibited no significant chromosomal alterations, while the third showed gain of the short arm of chromosome 11p. The latter finding has previously been described as characteristic of a subset of Spitz nevi. The 2 melanomas showed multiple copy number alterations characteristic of melanoma such as 1q amplification and chromosome 9 deletion. This study has shown the utility of array-based CGH as a potential molecular test in distinguishing Spitz nevus from melanoma. The assay is capable of using archival paraffin-embedded, formalin-fixed material; is technically easier to perform as compared with conventional CGH; is more sensitive than conventional CGH in being able to detect focal alterations; and can detect copy number alterations even with relatively small amounts of lesional tissue as is typical of many skin tumors. Series_type = clinical_history_design A clinical history design type is where the organisms clinical history of diagnosis, treatments, e.g. vaccinations, surgery etc. Keywords: other
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Project description:The purpose of this study was to comprehensively study and compare the molecular gene expression profiles of common melanocytic nevi (GSE53223), dysplastic nevi (GSE53223), and primary melanoma.
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Project description:Cellular and molecular differences between DNs and CMNs are not completely understood. Using cDNA microarray, quantitative RT-PCR, and immunohistochemistry, we molecularly characterized DNs and analyzed the difference between DNs and CMNs. total RNA was extratced from sliced full thickness tissue samples for both nevi samples. total RNA was extratced from bulk puch biopsy samples for normal skin.
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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.
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Project description:SN-38 resistant breast cancer cell lies (MCF-7 and MDA-MB-231) were established by stepwise increasing the concentration of SN-38. Gene expression profiling was performed on parental (sensitive) MCF-7 and parental (sensitive) MDA-MB-231 cell lines and their respective SN-38 resistant cell lines. For each cell line we harvested RNA from three independent passages and conducted 3 arrays.
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Project description:Human CD4+ T cells mediate spontaneous rejection of acquired benign melanocytic nevi, in the majority of cases, through a break in peripheral tolerance. For the remaining cases, nevi remain stable and do not progress to malignancy. In this experiment, we compared gene expression of post-transplant rejected nevi to stable nevi in order to better characterize their transcriptional profiles.
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Project description:A substantial part of cutaneous malignant melanomas develops from benign nevi. However, the precise molecular events driving the transformation from benign to malignant melanoma are not well understood. We used laser microdissection and mass spectrometry to analyze the proteomes of melanoma subtypes, including superficial spreading melanomas (SSM, n=17), nodular melanomas (NM, n=17), and acral melanomas (AM, n=15). Furthermore, we compared the proteomes of nevi cells and melanoma cells within the same specimens (nevus-associated melanoma (NAM, n=14)). In total, we quantified 7,935 proteins. Despite the genomic and clinical differences of the melanoma subtypes, our analysis revealed relatively similar proteomes, except for the upregulation of proteins involved in immune activation in NM vs AM. Examining NAM versus nevi, we found 1,725 differentially expressed proteins. Among these proteins were 140 that overlapped with cancer hallmarks, tumor suppressors, and regulators of metabolism and cell cycle. Pathway analysis indicated aberrant activation of the RAS/MAPK and PI3K-AKT-mTOR pathways, as well as the Hippo-YAP pathway. Using a classifier, we identified six proteins capable of distinguishing melanoma from nevi samples. Our study represents the first comprehensive comparative analysis of the proteome in melanoma subtypes and associated nevi, offering new insights into the biological behavior of these distinct entities.
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