NHGRI_Melanoma_class
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE1 | GEO | 2001/01/22
SECONDARY ACCESSION(S): PRJNA84463
REPOSITORIES: GEO
Similar Datasets
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.
2024-01-28 | PXD044107 | Pride
Project description:We investigated whether methylation in primary melanomas is associated with tumor pathologic features or defines subgroups of primary melanomas 47 primary cutaneous melanomas were analyzed using the Illumina GoldenGate Cancer Panel I methylation array
2015-06-15 | E-GEOD-54623 | biostudies-arrayexpress
Project description:Cutaneous, ocular and mucosal melanomas are histologically indistinguishable tumors that are driven by different spectrum of genetic alterations. With current methods, identification of the site of origin of a melanoma metastasis is challenging, in particular when the metastasis is the first tumor manifestation. Genome wide DNA methylation profiling has shown promise for the identification of the site of tumor origin in various settings. Here we explore the DNA methylation landscape of melanomas from different sites and analyze if different melanoma origins can be distinguished by their epigenetic profile. We performed DNA methylation analysis, next generation DNA panel sequencing and copy number analysis of 82 non-cutaneous and 25 cutaneous melanoma samples. We further analyzed eight normal melanocyte cell culture preparations by DNA methylation profiling. DNA methylation analysis clearly separated uveal melanomas from melanomas of other primary sites while mucosal, conjunctival and cutaneous melanomas were epigenetically almost identical. Still, we observed DNA methylation differences in cancer-related genes, such as low frequencies of RARB and CDKN2A promoter methylation in mucosal melanomas, while conjunctival melanomas frequently harbored APC promoter methylation. Furthermore, all investigated melanomas of the paranasal sinus showed loss of PTEN expression, mainly caused by promoter methylation. This was less frequently seen in melanomas of other sites. Copy number analysis revealed recurrent amplifications in mucosal melanomas, including chromosome 4q, 5p, 11q and 12q. Most melanomas of the oral cavity showed gains of chromosome 5p with TERT amplification while 11q amplifications were enriched in melanomas of the nasal cavity. Mucosal, conjunctival and cutaneous melanomas show a surprisingly similar DNA methylation profile and identification of the site of origin by DNA methylation testing is likely not feasible. Still, our study shows that there are DNA methylation differences on the gene level in known tumor drivers, related to the anatomical primary site.
2021-09-21 | GSE178416 | GEO
Project description:We performed microRNA sequencing of primary human FFPE Acral Melanoma (AM), Cutaneous Melanoma (CM), Acral Nevi (AN), and Cutaneous Nevi (CN). We found that previously identified ratios of microRNAs, particularly miR-21-5p and miR-211-5p, were able to accurately classify benign and malignant melanocytic neoplasia, both in non-acral cutaneous melanomas and nevi (CM vs CN), as well as matched acral melanoma and nevi (AM vs AN). Receiver operating characteristic area under the curve (AUC) of Ensemble models trained using these microRNA ratios demonstrated AUCs of 0.88-0.90 across these melanoma subtypes, suggesting the potential utility of these ratios as a biomarker of malignancy in melanocytic neoplasia.
2024-08-14 | GSE266413 | GEO
Project description:This series represent several subgroups of experiments designed to investigate the role of basal immunoglobulin signaling in immature B cell development. The first subgroup of arrays (Ctrl Mhi, Cre Mhi, Cre Mlo) was done to identify the changes in gene expression in immature B cells as a consequence of inducible deletion of surface IgM expression via Cre-LoxP mediated excision of Ig heavy chain. The second subgroup of arrays (GFPneg, GFPpos, FxE Ctrl, FxE HA) was done to identify the changes in gene expression in immature B cells as a consequence of blockade of tyrosine kinase signaling with herbimycin A treatment. The third subgroup of arrays (FxD, FxE, B6 Mneg, HEL Mhi) was done to establish gene expression profiles of immature B, pre B and pro B cells as reference platforms for the other two subgroups. (Tze etal. Public Library of Science Biology, 2005) The appended supplementary tables are described as follows: TABLE 1: Transformed array signal intensities used for statistical analysis. Listed are all probe sets excluding masked probe sets and Affymetrix hybridization control probe sets. Results are based on the following definitions: - Values with detection p values <0.1 were considered present. - Signal intensities with detection = "A" or with values < 20 were set to "20". TABLE 2: Genes differentially expressed between Ctrl Mhi and Cre Mlo cell populations and associated signal values. Results are based on the following definitions: - 2-fold or greater difference in means - difference in mean expression values > 200 - P < 0.01 (by Student's T test) TABLE 3: Probesets used for clustering in Figures 2 and 3 of publication TABLE 4: Probesets used for clustering in Figure 7 of publication TABLE 5: Correlation coefficients between all cell populations. Correlation coefficients were calculated as an additional method to demonstrate the relationship of the various cell populations to each other. Shown are the correlation coefficients generated using the mean expression values for each of the 101 transcripts from Figure 7 of publication. Keywords = bone marrow B cells
2005-02-03 | GSE2227 | GEO
Project description:Among the myriad tumors analyzed to date, cutaneous malignant melanomas bear some of the highest mutational burdens. Thus, it is somewhat surprising that oncogene exclusion between is so pronounced in melanomas where there is only a single melanoma out of 366 sequenced specimens which harbors concurrent BRAF(V600E/M) and NRAS(G13R) mutations (TCGA-ES-A2NC Sample; WWW.bioportal.org), In this senario some NRAS and BRAF mutations co-expressing cells show slow growth phenotypes by under study mechanism. We used Affymetrix GeneChip Expression Arrays to detail the global programme of gene expression underlying oncogenic exclusion and identified distinct classes of up and down-regulated genes during this process.
2018-11-22 | GSE122835 | GEO
Project description:Cutaneous malignant melanoma is among the most deadly human cancers, broadly resistant to most clinical therapies. A majority of patients with BRAFV600E melanomas respond well to inhibitors such as vemurafenib, but all ultimately relapse. Moreover, there are no viable treatment options available for other non-BRAF melanoma subtypes in the clinic. A key to improving treatment options lies in a better understanding of mechanisms underlying melanoma progression, which are complex and heterogeneous. In this study we perform gene expression profilling of highly and poorly malignant melanocytic tumors from genetically engineered mouse models to discover important drivers of cancer progression.
2017-02-01 | GSE87331 | GEO
Project description:Therapeutic screening of potential anticancer agents relies on representative cancer models. In vitro cell culture models have been long questioned to be representative for human malignant glioma. Therefore, in the present study genomic profiles of both short-term (2 weeks; n=8) and long-term (6 and 12 weeks; n=3) primary cell cultures and spheroid cultures were compared with their parental malignant gliomas. Cancer genomic profiles were obtained by 6400 BAC array comparative genomic hybridization. In 7 out of 8 short-term primary cell cultures, the genomic profiles clustered further from their parental tumors than the spheroid cultures. In 4 out of 8 samples, the changes were substantial and included chromosomal regions associated with prognosis and therapeutic response. The average correlation coefficients between parental tumor profiles and spheroid profiles was 0.89 (range: 0.79 to 0.97), whereas those between parental tumors and cell cultures was 0.62 (range: 0.10 to 0.96). In 2 out of 3 primary cell cultures progressive genetic changes appeared at 6 and 12 weeks after initial preservation, whereas the spheroid cultures were genetically stable throughout. It is concluded that the cancer genomic profile of primary cell cultures from malignant glioma is inconsistent with the parental tumor’s profile already after 2 weeks with subsequent progressive genetic changes. Because malignant glioma spheroids are genetically stable, biological characteristics of the parental tumor are better reflected. This indicates that the spheroid model is better for therapeutic screening. Keywords: comparative genomic hybridization
2007-02-01 | GSE6042 | GEO
Project description:Sulfur mustard (SM) is a potent alkylating agent. We are developing medical countermeasures to reduce the injury caused by SM exposure. Screening in the mouse ear vesicant model has identified three effective compounds: dimercaprol (British anti-lewisite), indomethacin, and octyl homovanillamide (OHV). To identify gene expression changes that correlate with compound efficacy we used oligonucleotide microarrays to compare gene expression profiles in vehicle-exposed skin, SM-exposed skin, and skin pretreated with each compound before SM exposure. Mice were topically exposed on the inner surface of the right ear to SM alone or pretreated for 15 min with one of the compounds and then exposed to SM. Left ears were vehicle-exposed. Ear tissue was harvested 24 hr later for ear weight determination (an endpoint indicating compound efficacy). The exposure groups were: methylene chloride (sulfur mustard vehicle); ethanol (drug vehicle); 0.08 mg sulfur mustard; 6.25 mg dimercaprol 15 min before 0.08 mg sulfur mustard; 1.34 mg indomethacin 15 min before 0.08 mg sulfur mustard; 0.6 mg octylhomovanillamide 15 min before 0.08 mg sulfur mustard; 6.25 mg dimercaprol alone; 1.34 mg indomethacin alone; 0.6 mg octylhomovanillamide alone. RNA was extracted from the tissues and used to generate oligonucleotide microarray probes. Principal component analysis of the gene expression data revealed partitioning of the samples based on drug treatment and SM exposure. Vehicle-exposed mouse ears clustered away from the other treatment groups. SM-exposed mouse ears pretreated with dimercaprol or OHV clustered more closely with vehicle-exposed ears, while SM-exposed mouse ears pretreated with indomethacin clustered more closely with SM-exposed ears. This clustering of the samples is supported by the ear weight data, in which the indomethacin group has ear weights closer to the SM-exposed group, whereas the dimercaprol and OHV groups have ear weights closer to the vehicle-exposed group. Correlation coefficients were calculated for each gene based on the correlation between gene expression level and ear weight. These data provide the basis for understanding what gene expression changes are important in the development of effective SM medical countermeasures. Keywords: ordered
2005-12-22 | GSE2950 | GEO
Project description:All cancers are diseases of the genome. A combination of somatic point mutations, focal amplifications and deletions, and chromosome level aberrations conspire to disrupt gene expression and the interplay between signaling pathways that control normal growth and tissue homeostasis. Here we investigate transcript levels in 7 melanomas and a pool of melanocytes. The transcriptome from 7 cutaneous melanomas and a pool of 2 normal melanocyte cultures was sequenced using the 454 technology
2011-04-07 | E-GEOD-22932 | biostudies-arrayexpress