Molecular characterization of mucosal melanomas
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA470997 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Molecular characterization of mucosal melanomas
| PRJNA470998 | ENA
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:Although identified as the key environmental driver of common cutaneous melanoma, the role of ultraviolet radiation (UVR)-induced DNA damage in mucosal melanoma is poorly defined. We present the largest cohort of mucosal melanomas of conjunctival origin to be analyzed by whole genome sequencing and show a predominance of UVR-associated single base substitution signature 7 (SBS7) in the majority of the samples. Our data shows mucosal melanomas with SBS7 dominance have similar genomic patterns to cutaneous melanomas and therefore this subset could benefit from treatments currently used for common cutaneous melanoma.
| EGAS00001004697 | EGA
Project description:Mucosal melanomas (MM) arise from mucosal melanocytes at different anatomical sites. MM are rare and highly aggressive, and their outcome is very poor. Only dismal clinical benefits have been obtained for the disseminated disease, with very limited promising results using approved immune checkpoint inhibitors. Compared to the cutaneous counterpart, data on the immunogenicity and IFN-γ sensitivity of MM are largely missing. Here, we explored these issues combining microscopy and -omics approaches on a set of unique sino-nasal melanoma (SN-MM) cell lines and clinical samples. All SN-MM cell lines display normal surface expression of IFNGR along with integrity of the IFNGR/JAK/STAT signaling pathway. Moreover, as a group, all SN-MM cell lines resulted responsive to the administration of IFN-γ as measured by transcriptomic and proteomic signatures. Specifically, IFN-γ induced canonical IFN-γ regulated genes involved in immune cell recognition and antigen presentation. In sixty percent of SN-MM cell lines IFN-γ also exerted a direct cytotoxic and anti-proliferative effect, release of CXCL10 and surface expression of CD274/PD-L1; the remaining fraction of SN-MM cell lines display IFN-γ functional refractoriness, likely dependent on post-transcriptional regulation of the IFN-γ regulated molecules. Analysis of clinical samples revealed that SN-MM are immune desert with scarce tumor-infiltrating lymphocytes (TILs), a feature predicting unfavourable outcomes; moreover, they resulted negative for CD274/PD-L1. This set of findings indicates that integration of functional precision oncology might refine the characterization of immune escape mechanisms to better allocate melanoma patients to various IT options.
2026-03-16 | PXD059186 | Pride
Project description:NanoString data on 12 conjunctival melanomas and mucosal melanoma The objective was to compare conjunctival melanoma with other mucosal melanomas at the RNA level using NanoString expression analysis of FFPE material.
2020-01-21 | GSE143952 | GEO
Project description:<p>Mucosal melanoma is a deadly disease that carries the worst prognosis amongst subtypes of melanoma. Like all melanomas, mucosal melanomas are frequently driven by activating mutations in the MAPK and/or PI3K pathways; however, unlike melanomas that arise on sun-exposed skin, mucosal melanomas harbor few point mutations. Instead, most somatic alterations involve structural alterations, which appear early during tumor progression. Molecular studies in mucosal melanoma generally only profile point mutations without interrogating copy number alterations, and pathogenic mutations are only found in 30% of cases. We sequenced 38 mucosal melanomas, and in addition to profiling point mutations, we looked for copy number alterations that amplify oncogenes or delete tumor suppressors.</p>
| phs001594 | dbGaP
Project description:Mucosal melanomas (MM) arise from mucosal melanocytes at various anatomical sites. These tumors are rare, highly aggressive, and often associated with poor outcomes. Current treatments, including immune checkpoint inhibitors, show limited efficacy in advanced disease. Compared to cutaneous melanomas, there is a lack of data on the immunogenicity and IFN-γ sensitivity of MM. In this study, we examine these features in sino-nasal melanoma (SN-MM) cell lines and clinical samples using microscopy and functional genomics. Microscopic analysis reveals that most SN-MM tumors are immune "desert" with few tumor-infiltrating lymphocytes (TILs), a characteristic linked to poor prognosis. Additionally, SN-MM tumors are CD274/PD-L1 negative. SN-MM cell lines express transcripts for melanocytic and cancer testis antigens. They also show normal surface expression of IFN-γ receptors (IFNGR) and maintain the integrity of the IFNGR/JAK/STAT signaling pathway. Transcriptomic and proteomic analyses demonstrate that SN-MM cell lines, as a group, respond to IFN-γ by upregulating genes involved in immune recognition and antigen presentation. In 60% of SN-MM lines, IFN-γ also induces cytotoxic and anti-proliferative effects, the release of CXCL10 and upregulation of CD274/PD-L1. The remaining SN-MM cell lines, characterized by poor differentiation, show refractoriness to these effects, likely due to post-transcriptional regulation. These findings suggest that combining functional precision oncology with immune context analysis could refine our understanding of immune escape mechanisms in MM and improve patient stratification for immune therapies.
2026-03-18 | GSE287519 | GEO
Project description:We conducted whole genome sequencing of 5 mucosal melanomas and their matched DNA from blood. We conducted whole exome sequencing of a further 5 mucosal melanomas and their matched DNA from blood.
| EGAS00001000474 | EGA
Project description:Molecular profiling of ADAM12+ MSCs in B16-OVA melanomas
| PRJNA852211 | ENA
Project description:Molecular Characterization of Hemimegalencephaly
| PRJNA671236 | ENA