Conjunctival and mucosal melanoma
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE143952 | GEO | 2020/01/21
REPOSITORIES: GEO
Similar Datasets
Project description:Conjunctival and mucosal melanoma
| PRJNA602317 | 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:<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: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:Purpose: To characterize the transcriptome and cellular the tumor microenvi-ronment of conjunctival melanoma (CM) compared to healthy conjunctiva and to analyze the transcriptional differences between CM with good and poor clinical outcome. Methods: Twelve formalin-fixed and paraffin-embedded (FFPE) CM of twelve patients were analyzed by Massive Analysis of cDNA Ends (MACE) RNA se-quencing. Six samples each with good and poor clinical outcome were exam-ined, the latter being defined by local recurrence or systemic metastases with a follow-up of at least 24 months. Eight age-matched healthy FFPE conjunctival specimens from eight patients who underwent retinal detachment surgery served as controls. Bioinformatic cell type enrichment analysis with xCell was used to characterize the tumor microenvironment (TME). Differentially expressed genes (DEG) and the associated biological processes were analyzed between CM and control conjunctiva. Additionally, a prognostic transcription profile was identified by comparing melanoma of good and poor clinical outcome. Results: The TME of conjunctival melanoma was characterized by the enrich-ment of melanocytes, pericytes and especially several immune cell types. Among them, plasmacytoid dendritic cells (pDC), natural killer T cells (NKT), B cells and mast cells were most significantly increased in CM compared to healthy conjunc-tiva. DEG between CM and control were mainly involved in biological processes such as inhibition of apoptosis, proteolysis and response to growth factors. POU3F3, BIRC5 and 7 were among the top expressed genes associated with inhibition of apoptosis. Twenty genes, among them CENPK, INHA, USP33 and CASP3, were identified as prognostically relevant factors reaching high classifi-cation accuracy (AUC: 1.0). Conclusions: The present study provides new insights into the TME and the transcriptional profile of CM and additionally identifies new prognostic bi-omarkers. These results might lead to new diagnostic and therapeutic options for CM.
2020-08-30 | GSE148387 | GEO
Project description:Mucosal Melanomas (MM) are highly aggressive neoplasms arising from mucosal melanocytes. Current treatments offer a limited survival benefit for patients with advanced MM; moreover, the lack of pre-clinical cellular systems has significantly limited the understanding of their immunobiology. By morphology, ultrastructure and phenotype analysis, this study reports the validation and functional characterization of five cell lines obtained from human melanomas arising from the sino-nasal mucosa and designated as SN-MM1-5. Compared to the normal counterpart, the proteomic profile of SN-MM is consistent with transformed melanocytes showing a heterogeneous degree of melanocytic differentiation and activation of cancer-related pathways. All SN-MM cell lines resulted tumorigenic in vivo in NOD/SCID mice. Of relevance, the microscopic analysis of the corresponding xenotransplants allowed the identification of clusters of MITF-/CDH1-/CDH2+/ZEB1+/CD271+ cells, supporting the existence of melanoma initiating cells also in MM, as confirmed on clinical samples. The proteomic analysis of SN-MM cell lines revealed that RICTOR, a subunit of mTORC2 complex, is the most significantly activated upstream regulator, suggesting a relevant role for the PI3K-Akt-mTOR pathway in these neoplasms. Accordingly, Akt activation, as measured by pAkt(Ser473) and pAkt(Thr308), was observed in all SN-MM and resulted constitutive and sustained by PTEN loss in SN-MM2 and SN-MM3 . A functional role for PI3K-Akt-mTOR pathway was confirmed by PI3K chemical inhibitor LY294002 which significantly impaired SN-MM cell lines viability. Overall, these novel and unique cellular systems represent relevant experimental tools for a better understanding of the immunobiology of these neoplasms and, as extension, to MM from other sites.
2024-01-26 | PXD037551 | Pride
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:FFPE tumor samples from metastatic melanoma patients were extracted and a Nanostring Wnt Pathway panel was performed
2021-01-29 | GSE165745 | GEO
Project description:Cutaneous, acral and mucosal subtypes of melanoma were evaluated by whole-genome sequencing, revealing genes affected by novel recurrent mutations to the promoter (TERT, DPH3, OXNAD1, RPL13A, RALY, RPL18A, AP2A1), 5’-UTR (HNRNPUL1, CCDC77, PES1), and 3’-UTR (DYNAP, CHIT1, FUT9, CCDC141, CDH9, PTPRT) regions. TERT promoter mutations had the highest frequency of any mutation, but neither they nor ATRX mutations, associated with the alternative telomere lengthening mechanism, were correlated with greater telomere length. Genomic landscapes largely reflected ultraviolet radiation mutagenesis in cutaneous melanoma and provided novel insights into melanoma pathogenesis. In contrast, acral and mucosal melanomas exhibited predominantly structural changes, and mutation signatures of unknown aetiology not previously identified in melanoma. The majority of melanomas had potentially actionable mutations, most of which were in components of the mitogen-activated protein kinase and phosphoinositol kinase pathways.
2017-12-01 | GSE80435 | GEO
Project description:Purpose: To identify the changes in postnatal mouse conjunctival forniceal gene expression and their regulation by Klf4 around eye opening stage when the goblet cells first appear. Methods: Laser-capture-microdissection was used to collect conjunctival forniceal epithelial cells from postnatal-day (PN) 9, PN14 and PN20 wild-type (WT), and PN14 Klf4-conditional null (Klf4CN) mice, where goblet cells are absent, developing, present, and missing, respectively. Microarrays were used to compare gene expression among these four groups. Expression of selected genes was validated by Q-RT-PCR, and spatiotemporal expression assessed by in situ hybridization. Results: We identified 668, 251, 1160 and 139 genes that were upregulated and 492, 377, 1419 and 57 genes that were downregulated between PN9 and PN14, PN14 and PN20, PN9 and PN20, and PN14 WT and Klf4CN conjunctiva, respectively. Transcription factors Spdef, FoxA1 and FoxA3 that regulate goblet cell development in other mucosal epithelia, and epithelial specific Ets (ESE) transcription factor family members were upregulated during conjunctival development. Mesenchymal-epithelial transition (MET) was favored and diverse pathways related to glycoprotein biosynthesis, mucosal immunity, signaling, endocytic and neural regulation were affected during conjunctival development. Conjunctival Klf4-target genes differed significantly from the previously identified corneal Klf4-target genes, implying tissue-dependant regulatory targets for Klf4. Conclusions: We have identified the changes in gene expression accompanying mouse conjunctival development and the role of Klf4 in this process. These studies provide new probes to study conjunctival epithelial development and function, and reveal that the gene regulatory network required for goblet cell development is conserved across different mucosal epithelia. Three independent samples in each of four developmental groups
2011-06-15 | E-GEOD-26076 | biostudies-arrayexpress