Similar Datasets
Project description:Single-cell sequencing analysis reveals the tissue architecture and empowers clinical trial in advanced conjunctival melanoma
| PRJNA900194 | ENA
Project description: Not available
| S-EPMC6323549 | biostudies-literature
Project description:The authors present 2 patients with locally advanced conjunctival melanoma for whom definitive surgery would mean an orbital exenteration with its associated inherent total visual loss and major facial disfigurement. Instead both patients were treated with immune checkpoint inhibitor therapy. In 1 patient neoadjuvant pembrolizumab was used for approximately 12 months and the patient experienced near-total clinical resolution of the conjunctival melanoma. Multiple surgical biopsies of very small residual pigmentation showed pigmented macrophages and a complete pathologic response. In the second patient who presented with a locally advanced and metastatic conjunctival melanoma, significant shrinkage of conjunctival mass was observed after treatment with a combination of ipilimumab and nivolumab for 5 months, and this allowed preservation of the eye and ocular function.
| S-EPMC7744319 | biostudies-literature
Project description:BACKGROUND:Conjunctival melanoma is a potentially deadly eye tumour. Despite effective local therapies, tumour recurrence and metastasis remain frequent. The genetics of conjunctival melanomas remain incompletely understood. METHODS:A large cohort of 63 conjunctival melanomas was screened for gene mutations known to be important in other melanoma subtypes by targeted next-generation sequencing. Mutation status was correlated with patient prognosis. RESULTS:Frequent mutations in genes activating the MAP kinase pathway were identified. NF1 mutations were most frequent (n = 21, 33%). Recurrent activating mutations were also identified in BRAF (n = 16, 25%) and RAS genes (n = 12, 19%; 11 NRAS and 1 KRAS). CONCLUSIONS:Similar to cutaneous melanomas, conjunctival melanomas can be grouped genetically into four groups: BRAF-mutated, RAS-mutated, NF1-mutated and triple wild-type melanomas. This genetic classification may be useful for assessment of therapeutic options for patients with metastatic conjunctival melanoma.
| S-EPMC5943412 | biostudies-literature
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:Purpose:To assess the role of the canonical Wnt pathway via activation of ?-catenin in tumor progression of conjunctival melanoma. Methods:?-Catenin localization was assessed by immunohistochemistry in 43 conjunctival nevi, 48 primary acquired melanoses (PAM; conjunctival melanocytic intraepithelial neoplasia), and 44 conjunctival melanomas. Activation of the canonical or the noncanonical Wnt pathway was tested in vitro in 4 conjunctival melanoma cell lines with stimulation of either Wnt5a or Wnt3a. Wound healing assays were performed with Wnt5a. Results:Nuclear ?-catenin expression was found in 16% of the nevi, in 15% of the melanomas, and in 4% of the PAM. Membranous ?-catenin expression was identified in all the nevi and PAM and in 97.7% of the melanomas. In vitro, Wnt5a stimulation in the 4 conjunctival melanomas and in 1 skin melanoma cell line did not induce nuclear translocation of ?-catenin, nor did it increase cell motility in the wound healing assays. Wnt3a stimulation did not induce nuclear localization of ?-catenin in any of the cell lines tested. Conclusions:In conjunctival melanoma, nuclear localization and activation of ?-catenin appear to be limited, suggesting that inhibition of ARF6, responsible for ?-catenin activation, in subsets of skin melanoma may not represent a treatment option for this tumor. In vitro, Wnt3a or Wnt5a did not induce nuclear ?-catenin localization.
| S-EPMC6827456 | biostudies-literature
Project description:Conjunctival melanoma (CJM) is a rare but potentially lethal and highly-recurrent cancer of the eye. Similar to cutaneous melanoma (CM), it originates from melanocytes. Unlike CM, however, CJM is relatively poorly characterized from a genomic point of view. To fill this knowledge gap and gain insight into the genomic nature of CJM, we performed whole-exome (WES) or whole-genome sequencing (WGS) of tumor-normal tissue pairs in 14 affected individuals, as well as RNA sequencing in a subset of 11 tumor tissues. Our results show that, similarly to CM, CJM is also characterized by a very high mutation load, composed of approximately 500 somatic mutations in exonic regions. This, as well as the presence of a UV light-induced mutational signature, are clear signs of the role of sunlight in CJM tumorigenesis. In addition, the genomic classification of CM proposed by TCGA seems to be well-applicable to CJM, with the presence of four typical subclasses defined on the basis of the most frequently mutated genes: BRAF, NF1, RAS, and triple wild-type. In line with these results, transcriptomic analyses revealed similarities with CM as well, namely the presence of a transcriptomic subtype enriched for immune genes and a subtype enriched for genes associated with keratins and epithelial functions. Finally, in seven tumors we detected somatic mutations in ACSS3, a possible new candidate oncogene. Transfected conjunctival melanoma cells overexpressing mutant ACSS3 showed higher proliferative activity, supporting the direct involvement of this gene in the tumorigenesis of CJM. Altogether, our results provide the first unbiased and complete genomic and transcriptomic classification of CJM.
| S-EPMC7775126 | biostudies-literature
Project description:Conjunctival and mucosal melanoma
| PRJNA602317 | ENA
Project description:Relatively little is known about the genetic aberrations of conjunctival melanomas (CoM) and their correlation with clinical and histomorphological features as well as prognosis. The aim of this large collaborative multicenter study was to determine potential key biomarkers for metastatic risk and any druggable targets for high metastatic risk CoM. Using Affymetrix single nucleotide polymorphism genotyping arrays on 59 CoM, we detected frequent amplifications on chromosome (chr) 6p and deletions on 7q, and characterized mutation-specific copy number alterations. Deletions on chr 10q11.21-26.2, a region harboring the tumor suppressor genes, PDCD4, SUFU, NEURL1, PTEN, RASSF4, DMBT1, and C10orf90 and C10orf99, significantly correlated with metastasis (Fisher's exact, p ? 0.04), lymphatic invasion (Fisher's exact, p ? 0.02), increasing tumor thickness (Mann-Whitney, p ? 0.02), and BRAF mutation (Fisher's exact, p ? 0.05). This enhanced insight into CoM biology is a step toward identifying patients at risk of metastasis and potential therapeutic targets for systemic disease.
| S-EPMC6849808 | biostudies-literature
Project description:Relatively little is known about the genetic aberrations of conjunctival melanomas (CoM) and their correlation with clinical and histomorphological features as well as prognosis. The aim of this large collaborative multicentre study was to determine potential key biomarkers for metastatic risk and any druggable targets for high-risk metastatic CoM. Using Affymetrix Single Nucleotide Polymorphism genotyping arrays on 59 CoM, we detected frequent amplifications on chromosome (chr) 6p and deletions on 7q, and characterised mutation-specific copy number alterations. Deletions on chr 10q11.21-26.2, a region harbouring the tumor suppressor genes, PDCD4, SUFU, NEURL1, PTEN, RASSF4, DMBT1 and C10orf90 & 99 significantly correlated with metastases (Fisher’s Exact, p≤0.04), lymphatic invasion (Fisher’s Exact, p≤0.02), increasing tumor thickness (Mann-Whitney, p≤0.02) and BRAF mutation (Fisher’s Exact, p≤0.05). This enhanced insight into CoM biology is a step towards identifying patients at risk of metastasis and potential therapeutic targets for systemic disease.
2019-11-25 | GSE123011 | GEO