Low-Pass Whole-Genome Sequencing as a Method of Determining Copy Number Variations in Uveal Melanoma Tissue Samples

Publication date: Available online 22 January 2020Source: The Journal of Molecular DiagnosticsAuthor(s): Aaron B. Beasley, Jacqueline Bentel, Richard J.N. Allcock, Tersia Vermeulen, Leslie Calapre, Timothy Isaacs, Melanie R. Ziman, Fred K. Chen, Elin S. GrayAnalysis of specific somatic copy number alterations (SCNAs) using multiplex ligation-dependent probe amplification (MLPA) is used routinely as a prognostic test for uveal melanoma (UM). This technique requires relatively large amounts of input DNA, unattainable from many small fine-needle aspirate biopsy specimens. Herein, we compared the use of MLPA with whole-genome amplification (WGA) combined with low-pass whole-genome sequencing (LP-WGS) for detection of SCNA profiles in UM biopsy specimens. DNA was extracted from 21 formalin-fixed, paraffin-embedded UM samples and SCNAs were assessed using MLPA and WGA followed by LP-WGS. Cohen's κ was used to assess the concordance of copy number calls of each individual chromosome arm for each patient. MLPA and WGA/LP-WGS detection of SCNAs in chromosomes 1p, 3, 6, and 8 were compared and found to be highly concordant with a Cohen's κ of 0.856 (bias-corrected and accelerated 95% CI, 0.770–0.934). Only 13 of 147 (8.8%) chromosomal arms investigated resulted in discordant calls, predominantly SCNAs detected by WGA/LP-WGS but not MLPA. These results indicate that LP-WGS might be a suitable alternative or adjunct to MLPA for the detection of SCNAs associated with pro...
Source: The Journal of Molecular Diagnostics - Category: Pathology Source Type: research

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Uveal melanoma (UM) is the most common primary intraocular carcinoma in adults. Cinobufagin, secreted by the Asiatic toad Bufo gargarizans, is a traditional Chinese medicine, widely used in tumor treatment. Here, we explored the potential antitumor function of cinobufagin and investigated its biochemical mechanisms in UM cells. The antitumor potential of cinobufagin was determined via cell viability, cell cycle, and apoptosis assays. Colony formation assays confirmed that cinobufagin exerted potent antitumor activity in a dose-dependent manner. We found that cinobufagin could induce cell apoptosis and upregulate the expres...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Carmona-Sáez Rodríguez-Manzaneque Extracellular matrix remodeling within the tumor microenvironment has been recognized as a relevant dynamic framework during tumor growth. However, research on proteases that trigger this remodeling keeps revealing a wide range of actions including both pro- and anti-tumorigenic. The extracellular protease ADAMTS1 exemplifies this dual role. In this work, we first confirmed a positive correlation of ADAMTS1 with endothelial-like phenotype of human melanoma cells together with the finding of associated signatures, including key genes such as endothelial CDH5. Using a C...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
ConclusionUnilateral raised intraocular pressure, iris neovascularization, or both may be the presenting features of intraocular tumors. High degree of suspicion and a thorough examination reveals the definitive diagnosis.
Source: International Ophthalmology - Category: Opthalmology Source Type: research
ris Behrmann Stephanie Kreis Reduced levels of intratumoural oxygen are associated with hypoxia-induced pro-oncogenic events such as invasion, metabolic reprogramming, epithelial–mesenchymal transition, metastasis and resistance to therapy, all favouring cancer progression. Small extracellular vesicles (EV) shuttle various cargos (proteins, miRNAs, DNA and others). Tumour-derived EVs can be taken up by neighbouring or distant cells in the tumour microenvironment, thus facilitating intercellular communication. The quantity of extracellular vesicle secretion and their composition can vary with changing microe...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Single Cell Analysis Reveals New Evolutionary Complexity in Uveal Melanoma  (study page |release notes)
Source: dbGaP, the database of Genotypes and Phenotypes - Category: Genetics & Stem Cells Tags: StudyRelease Source Type: research
Conclusion: Incidence of uveal melanoma increased by significant APC and varied between genders. Determinants of survival included age at diagnosis, AJCC stage, and radiation therapy. PMID: 32148939 [PubMed]
Source: Journal of Ophthalmology - Category: Opthalmology Tags: J Ophthalmol Source Type: research
Ipilimumab and nivolumab are immune checkpoint inhibitors used in the treatment of metastatic melanoma. The authors report the case of a 62-year-old white male individual with metastatic choroidal melanoma who had commenced adjuvant systemic treatment with combination checkpoint inhibitor therapy of intravenous ipilimumab (anti-cytotoxic T-lymphocyte antigen-4) and nivolumab (anti-programmed cell death-1) at 3-week cycle intervals. On day 4 after the second cycle, he developed an acute widespread rash. On examination there was confluent erythema with bullae and epidermal loss over 60% of the body surface area, with severe ...
Source: Journal of Immunotherapy - Category: Allergy & Immunology Tags: Clinical Studies Source Type: research
Uveal melanoma is a life-threatening disease for which data on germline predisposition are essentially limited to mutations in the BAP1 gene. Many risk factors are shared between uveal melanoma and cutaneous melanoma, and these include fair skin color and light eye color. We carried out a genome-wide association study on 590 uveal melanoma patients and 5199 controls. Using a P-value limit of 10−5 we identified 11 loci with related odds ratios for the risk alleles ranging from 1.32 to 1.78. The smallest P-value in the overall analysis reached 1.07 × 10−7 for rs3759710 at 14q32.11, which is intronic to TDP1...
Source: Melanoma Research - Category: Cancer & Oncology Tags: Original Articles: Translational Research Source Type: research
Publication date: Available online 4 March 2020Source: Carbohydrate PolymersAuthor(s): Jipeng Li, Yudong Xue, Jun Tian, Zeyang Liu, Ai Zhuang, Ping Gu, Huifang Zhou, Weian Zhang, Xianqun Fan
Source: Carbohydrate Polymers - Category: Biomedical Science Source Type: research
Hepatic metastasis develops in ~  50% of uveal melanoma (UM) patients with no effective treatments. Although GNAQ/GNA11 mutations are believed to confer pathogenesis of UM, the underlying mechanism of liver met...
Source: Molecular Cancer - Category: Cancer & Oncology Authors: Tags: Research Source Type: research
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