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Cancer Aug 2016Melanomas of the choroid, ciliary body, and iris of the eye are collectively known as uveal melanomas. These cancers represent 5% of all melanoma diagnoses in the United... (Review)
Review
Melanomas of the choroid, ciliary body, and iris of the eye are collectively known as uveal melanomas. These cancers represent 5% of all melanoma diagnoses in the United States, and their age-adjusted risk is 5 per 1 million population. These less frequent melanomas are dissimilar to their more common cutaneous melanoma relative, with differing risk factors, primary treatment, anatomic spread, molecular changes, and responses to systemic therapy. Once uveal melanoma becomes metastatic, therapy options are limited and are often extrapolated from cutaneous melanoma therapies despite the routine exclusion of patients with uveal melanoma from clinical trials. Clinical trials directed at uveal melanoma have been completed or are in progress, and data from these well designed investigations will help guide future directions in this orphan disease. Cancer 2016;122:2299-2312. © 2016 American Cancer Society.
Topics: Chromosome Aberrations; Combined Modality Therapy; Early Detection of Cancer; Genetic Predisposition to Disease; Genetic Testing; Humans; Melanoma; Mutation; Neoplasm Metastasis; Neoplasm Staging; Prognosis; Research; Treatment Outcome; Uveal Neoplasms
PubMed: 26991400
DOI: 10.1002/cncr.29727 -
European Journal of Cancer (Oxford,... May 2021The rising interest for precise characterization of the tumour immune contexture has recently brought forward the high potential of RNA sequencing (RNA-seq) in... (Review)
Review
The rising interest for precise characterization of the tumour immune contexture has recently brought forward the high potential of RNA sequencing (RNA-seq) in identifying molecular mechanisms engaged in the response to immunotherapy. In this review, we provide an overview of the major principles of single-cell and conventional (bulk) RNA-seq applied to onco-immunology. We describe standard preprocessing and statistical analyses of data obtained from such techniques and highlight some computational challenges relative to the sequencing of individual cells. We notably provide examples of gene expression analyses such as differential expression analysis, dimensionality reduction, clustering and enrichment analysis. Additionally, we used public data sets to exemplify how deconvolution algorithms can identify and quantify multiple immune subpopulations from either bulk or single-cell RNA-seq. We give examples of machine and deep learning models used to predict patient outcomes and treatment effect from high-dimensional data. Finally, we balance the strengths and weaknesses of single-cell and bulk RNA-seq regarding their applications in the clinic.
Topics: Artificial Intelligence; Biomarkers, Tumor; Clinical Decision-Making; Gene Expression Profiling; Humans; Neoplasms; Precision Medicine; Predictive Value of Tests; Prognosis; RNA, Neoplasm; RNA-Seq; Single-Cell Analysis; Transcriptome; Tumor Microenvironment
PubMed: 33866228
DOI: 10.1016/j.ejca.2021.03.005 -
The British Journal of Ophthalmology Jan 2017Uveal melanoma represents ∼85% of all ocular melanomas and up to 50% of patients develop metastatic disease. Metastases are most frequently localised to the liver and,... (Review)
Review
Uveal melanoma represents ∼85% of all ocular melanomas and up to 50% of patients develop metastatic disease. Metastases are most frequently localised to the liver and, as few patients are candidates for potentially curative surgery, this is associated with a poor prognosis. There is currently little published evidence for the optimal management and treatment of metastatic uveal melanoma and the lack of effective therapies in this setting has led to the widespread use of systemic treatments for patients with cutaneous melanoma. Uveal and cutaneous melanomas are intrinsically different diseases and so dedicated management strategies and therapies for uveal melanoma are much needed. This review explores the biology of uveal melanoma and how this relates to ongoing trials of targeted therapies in the metastatic disease setting. In addition, we consider the options to optimise patient management and care.
Topics: Humans; Incidence; Liver Neoplasms; Melanoma; Molecular Biology; Molecular Targeted Therapy; Neoplasm Metastasis; Prognosis; Uveal Neoplasms
PubMed: 27574175
DOI: 10.1136/bjophthalmol-2016-309034 -
Eye (London, England) Feb 2017Although it is a relatively rare disease, primarily found in the Caucasian population, uveal melanoma is the most common primary intraocular tumor in adults with a mean... (Review)
Review
Although it is a relatively rare disease, primarily found in the Caucasian population, uveal melanoma is the most common primary intraocular tumor in adults with a mean age-adjusted incidence of 5.1 cases per million per year. Tumors are located either in iris (4%), ciliary body (6%), or choroid (90%). The host susceptibility factors for uveal melanoma include fair skin, light eye color, inability to tan, ocular or oculodermal melanocytosis, cutaneous or iris or choroidal nevus, and BRCA1-associated protein 1 mutation. Currently, the most widely used first-line treatment options for this malignancy are resection, radiation therapy, and enucleation. There are two main types of radiation therapy: plaque brachytherapy (iodine-125, ruthenium-106, or palladium-103, or cobalt-60) and teletherapy (proton beam, helium ion, or stereotactic radiosurgery using cyber knife, gamma knife, or linear accelerator). The alternative to radiation is enucleation. Although these therapies achieve satisfactory local disease control, long-term survival rate for patients with uveal melanoma remains guarded, with risk for liver metastasis. There have been advances in early diagnosis over the past few years, and with the hope survival rates could improve as smaller tumors are treated. As in many other cancer indications, both early detection and early treatment could be critical for a positive long-term survival outcome in uveal melanoma. These observations call attention to an unmet medical need for the early treatment of small melanocytic lesions or small melanomas in the eye to achieve local disease control and vision preservation with the possibility to prevent metastases and improve overall patient survival.
Topics: Age Distribution; Combined Modality Therapy; Humans; Incidence; Iridectomy; Melanoma; Radiosurgery; Radiotherapy; Risk Factors; Sex Distribution; Tumor Suppressor Proteins; Ubiquitin Thiolesterase; Ultraviolet Rays; Uveal Neoplasms
PubMed: 27911450
DOI: 10.1038/eye.2016.275 -
Proceedings of the National Academy of... May 2023Alternative splicing (AS) is prevalent in cancer, generating an extensive but largely unexplored repertoire of novel immunotherapy targets. We describe soform peptides...
Alternative splicing (AS) is prevalent in cancer, generating an extensive but largely unexplored repertoire of novel immunotherapy targets. We describe soform peptides from NA splicing for mmunotherapy target creening (IRIS), a computational platform capable of discovering AS-derived tumor antigens (TAs) for T cell receptor (TCR) and chimeric antigen receptor T cell (CAR-T) therapies. IRIS leverages large-scale tumor and normal transcriptome data and incorporates multiple screening approaches to discover AS-derived TAs with tumor-associated or tumor-specific expression. In a proof-of-concept analysis integrating transcriptomics and immunopeptidomics data, we showed that hundreds of IRIS-predicted TCR targets are presented by human leukocyte antigen (HLA) molecules. We applied IRIS to RNA-seq data of neuroendocrine prostate cancer (NEPC). From 2,939 NEPC-associated AS events, IRIS predicted 1,651 epitopes from 808 events as potential TCR targets for two common HLA types (A*02:01 and A*03:01). A more stringent screening test prioritized 48 epitopes from 20 events with "neoantigen-like" NEPC-specific expression. Predicted epitopes are often encoded by microexons of ≤30 nucleotides. To validate the immunogenicity and T cell recognition of IRIS-predicted TCR epitopes, we performed in vitro T cell priming in combination with single-cell TCR sequencing. Seven TCRs transduced into human peripheral blood mononuclear cells (PBMCs) showed high activity against individual IRIS-predicted epitopes, providing strong evidence of isolated TCRs reactive to AS-derived peptides. One selected TCR showed efficient cytotoxicity against target cells expressing the target peptide. Our study illustrates the contribution of AS to the TA repertoire of cancer cells and demonstrates the utility of IRIS for discovering AS-derived TAs and expanding cancer immunotherapies.
Topics: Male; Humans; RNA Precursors; Alternative Splicing; Leukocytes, Mononuclear; Receptors, Antigen, T-Cell; Epitopes, T-Lymphocyte; Immunotherapy; Antigens, Neoplasm; Peptides; Neoplasms
PubMed: 37192158
DOI: 10.1073/pnas.2221116120 -
Ugeskrift For Laeger May 2023Melanoma isolated to the iris is rare and can present with a distorted pupil. This is a case report of an 81-year-old asymptomatic man, who had a large pigmented element...
Melanoma isolated to the iris is rare and can present with a distorted pupil. This is a case report of an 81-year-old asymptomatic man, who had a large pigmented element in his left iris through 30 years. Because of involvement of the angle the tumour was excised with the ciliary body, and histopathologic examination revealed an iris melanoma. The aim of this report is to underscore the clinical signs of an iris melanoma and when surgery is needed.
Topics: Male; Humans; Aged, 80 and over; Pupil; Iris Neoplasms; Iris; Melanoma
PubMed: 37170744
DOI: No ID Found -
Asia-Pacific Journal of Ophthalmology... 2020Intraocular tumors are primarily diagnosed clinically. However, ancillary tests such as fluorescein angiogram provides excellent visualization of retinal tumors while... (Review)
Review
Intraocular tumors are primarily diagnosed clinically. However, ancillary tests such as fluorescein angiogram provides excellent visualization of retinal tumors while indocyanine green angiography reveals intrinsic vascular patterns of choroidal tumors. In this review, we contrast angiographic patterns of a variety of retinal, choroidal, and iris tumors.
Topics: Choroid; Eye Neoplasms; Fluorescein Angiography; Fundus Oculi; Humans; Retina
PubMed: 32960821
DOI: 10.1097/APO.0000000000000323 -
Archives of Pathology & Laboratory... Feb 2008The iris is the least common site of primary uveal melanoma. The prognosis of iris melanoma is better than that of melanoma of the ciliary body and choroid, but the... (Review)
Review
The iris is the least common site of primary uveal melanoma. The prognosis of iris melanoma is better than that of melanoma of the ciliary body and choroid, but the reason for this difference is unclear. One possible explanation is that iris melanoma is smaller than its posterior segment counterparts at the time of diagnosis. Most iris melanomas are spindle cell types, according to a modified Callender classification system. There is evidence that the proliferation of melanocytes of the anterior iris surface (iris plaque) and diffuse stromal invasion may be risk factors for local recurrence and metastasis, respectively.
Topics: Biomarkers, Tumor; Humans; Immunohistochemistry; Iris Neoplasms; Melanoma; Middle Aged; Prognosis; Survival Rate
PubMed: 18251588
DOI: 10.5858/2008-132-268-IM -
Survey of Ophthalmology 2020Intraocular leiomyoma is a benign smooth muscle tumor. First recognized before the era of immunohistochemistry, uveal leiomyomas have been described in case reports and... (Review)
Review
Intraocular leiomyoma is a benign smooth muscle tumor. First recognized before the era of immunohistochemistry, uveal leiomyomas have been described in case reports and small case series. We add 3 new cases, for a total of 80. Of these, there were 29 men and 51 women. The mean and median ages were 35.8 and 30.5 years respectively, with a range of 8 to 80 years. Curiously, ciliary body tumors were more common in females, whereas iris and posterior choroidal leiomyomas were more prevalent in males. Infrequently associated with systemic fibroids, nuclear expression of sex steroid receptors was inconsistent. Iris and posterior choroidal leiomyoma were predominantly amelanotic, while 40% of ciliary body leiomyomas were brown. Two-thirds of the leiomyomas blocked transillumination partially or completely, a feature shared by uveal melanoma. In general, low-frequency ultrasound imaging reveals low to moderate internal reflectivity; however, high-frequency anterior uveal ultrasound was used to localize a leiomyoma as resident in the suprachoroidal space with an overlying layer of intact choroid. In the few cases examined by physiologic imaging, increased metabolic activity (typically associated with malignancy and inflammation) has been noted. We found that pigmented uveal leiomyomas can be clinically identical to melanoma. Therefore, histopathology with immunohistochemical staining for smooth muscle actin was the most reliable diagnostic method to differentiate pigmented uveal leiomyoma from melanoma. Treatment is governed by the clinical diagnosis, tumor size and location, as well as prognosis for vision and globe preservation.
Topics: Adult; Eye Neoplasms; Female; Humans; Leiomyoma; Male; Middle Aged; Uvea
PubMed: 31923479
DOI: 10.1016/j.survophthal.2019.12.008