Uveal Melanoma

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Arun D. Singh - One of the best experts on this subject based on the ideXlab platform.

  • Uveal Melanoma: Metastases
    Clinical Ophthalmic Oncology, 2019
    Co-Authors: Pauline Funchain, Ahmad Tarhini, Arun D. Singh
    Abstract:

    Although there are effective treatments for primary Uveal Melanoma, the prognosis for metastatic disease is poor. There is no curative therapy for metastatic Uveal Melanoma, but options include local interventions such as surgical resection, chemoembolization, radioembolization, radiofrequency ablation, or systemic therapy including chemotherapy, targeted therapy, and immunotherapy.

  • Blood biomarkers for Uveal Melanoma.
    Future oncology (London England), 2012
    Co-Authors: Pierre L. Triozzi, Arun D. Singh
    Abstract:

    Uveal Melanoma disseminates hematogenously, and blood biomarkers may be useful for prognosis and for monitoring disease progression. Melanoma-associated, metastatic and immune factors have been measured in the blood of patients with Uveal Melanoma, as have circulating Melanoma cells. Most of the biomarkers were derived from studies in cutaneous Melanoma. For various biological and/or technical reasons, these assessments have not demonstrated the accuracy required for effective prognostic or monitoring assays. Advances in Uveal Melanoma genomics and proteomics have generated many candidate biomarkers that are potentially measurable in blood. Measuring circulating nucleic acids may also be possible. Improvements in molecular profiling techniques that accurately predict metastatic risk in Uveal Melanoma patients should facilitate biomarker discovery and aid implementation in clinical testing. The stage is set to translate the advances made in understanding the molecular characteristics of Uveal Melanoma in o...

  • Targeted therapy for Uveal Melanoma.
    Cancer treatment reviews, 2008
    Co-Authors: Pierre L. Triozzi, Charis Eng, Arun D. Singh
    Abstract:

    Uveal Melanoma is the most common primary intra-ocular malignancy in adults. Overall mortality rate remains high because of the development of metastatic disease, which is highly resistant to systemic therapy. Improved understanding of the molecular pathogenesis of cancers has led to a new generation of therapeutic agents that interfere with a specific pathway critical in tumor development or progression. Although no specific genes have been linked to the pathogenesis of Uveal Melanoma, which differs from that of cutaneous Melanoma, progress has been made in identifying potential targets involved in Uveal Melanoma apoptosis, proliferation, invasion, metastasis, and angiogenesis. This review focuses on the prospects for improving the systemic therapy of Uveal Melanoma using molecularly targeted agents that are currently in clinical use as well as agents being tested in clinical trials. Preclinical studies suggest potential benefit of inhibitors of Bcl-2, ubiquitin-proteasome, histone deactylase, mitogen-activated protein kinase and phosphatidylinositol-3-kinase-AKT pathways, and receptor tyrosine kinases. Modifiers of adhesion molecules, matrix metalloproteinase, and angiogenic factors also have demonstrated potential benefit. Clinical trials of some of these approaches have been initiated in patients with metastatic Uveal Melanoma as well as in the adjuvant setting after primary therapy.

  • Uveal Melanoma epidemiologic aspects
    Ophthalmology Clinics of North America, 2005
    Co-Authors: Arun D. Singh, Louise Bergman, Stefan Seregard
    Abstract:

    Melanomas of the ocular and adnexal structures comprise approximately 5% of all Melanomas. The majority (85%) of ocular Melanomas are Uveal in origin; primary conjunctival and orbital Melanomas are rare. The diagnosis of Uveal Melanoma is made by clinical examination including indirect ophthalmoscopy and by ancillary studies such as fluorescein angiography and ultrasonography. Metastases to the liver develop within 15 years after the initial diagnosis and treatment in approximately 50% of patients with posterior Uveal Melanoma; however, clinically evident metastatic disease at the time of initial presentation is uncommon, indicating that there is early subclinical metastasis in most cases.

  • Metastatic Uveal Melanoma
    Ophthalmology clinics of North America, 2005
    Co-Authors: Arun D. Singh, Ernest C. Borden
    Abstract:

    In general, the survival of patients with metastatic Uveal Melanoma is poor with a median survival of less than 6 months. Despite recent advances in management of Uveal Melanoma, the relative survival rate appears to have remained unchanged over the last 25 years. In this chapter, the pathogenesis, clinical features, and treatment of metastatic Uveal Melanoma are outlined.

Jerry A. Shields - One of the best experts on this subject based on the ideXlab platform.

  • Uveal Melanoma: Estimating prognosis
    Wolters Kluwer Medknow Publications, 2015
    Co-Authors: Swathi Kaliki, Carol L. Shields, Jerry A. Shields
    Abstract:

    Uveal Melanoma is the most common primary malignant tumor of the eye in adults, predominantly found in Caucasians. Local tumor control of Uveal Melanoma is excellent, yet this malignancy is associated with relatively high mortality secondary to metastasis. Various clinical, histopathological, cytogenetic features and gene expression features help in estimating the prognosis of Uveal Melanoma. The clinical features associated with poor prognosis in patients with Uveal Melanoma include older age at presentation, male gender, larger tumor basal diameter and thickness, ciliary body location, diffuse tumor configuration, association with ocular/oculodermal melanocytosis, extraocular tumor extension, and advanced tumor staging by American Joint Committee on Cancer classification. Histopathological features suggestive of poor prognosis include epithelioid cell type, high mitotic activity, higher values of mean diameter of ten largest nucleoli, higher microvascular density, extravascular matrix patterns, tumor-infiltrating lymphocytes, tumor-infiltrating macrophages, higher expression of insulin-like growth factor-1 receptor, and higher expression of human leukocyte antigen Class I and II. Monosomy 3, 1p loss, 6q loss, and 8q and those classified as Class II by gene expression are predictive of poor prognosis of Uveal Melanoma. In this review, we discuss the prognostic factors of Uveal Melanoma. A database search was performed on PubMed, using the terms "uvea," "iris," "ciliary body," "choroid," "Melanoma," "Uveal Melanoma" and "prognosis," "metastasis," "genetic testing," "gene expression profiling." Relevant English language articles were extracted, reviewed, and referenced appropriately

  • Overview of Management of Posterior Uveal Melanoma
    Radiotherapy of Intraocular and Orbital Tumors, 2003
    Co-Authors: Jerry A. Shields, Carol L. Shields, Luther W. Brady, Bizhan Micaily
    Abstract:

    In the first edition of this textbook, we stressed the controversies in management of Melanomas of the ciliary body and choroid (posterior Uveal Melanoma). Many of the controversies have been largely resolved, and there continue to be new developments related to the management of patients with posterior Uveal Melanoma. Therefore, it seems appropriate in this chapter to provide a brief overview of the current options in management of this important intraocular tumor. Other authors will discuss the details of radiation therapy of Uveal Melanoma.

  • Uveal Melanoma in young patients.
    Archives of ophthalmology (Chicago Ill. : 1960), 2000
    Co-Authors: Arun D. Singh, Carol L. Shields, Jerry A. Shields, Takami Sato
    Abstract:

    Objective To study the clinical profile of young patients with Uveal Melanoma. Design Retrospective case-control series. Setting Tertiary referral center. Patients Data on 63 patients aged 20 years or younger with Uveal Melanoma were reviewed for clinical profile and association with oculo(dermal) melanocytosis, familial Uveal Melanoma, dysplastic nevus syndrome, cutaneous Melanoma, and other second malignant neoplasms. Results Of 8000 patients with Uveal Melanoma, 63 (0.8%) were found in patients who were 20 years of age or younger. The median age at diagnosis was 16 years, and the youngest patient was 3 years old. Sixty-two patients (98%) were white, and Uveal Melanoma was unilateral in all cases. Seven patients (11%) had oculo(dermal) melanocytosis. Two patients (3%) had dysplastic nevi syndrome, and personal history of cutaneous Melanoma was observed in 1 patient (2%). No other second cancers were present in any patient. The 5- and 15-year posttreatment survival estimates were 0.95 (95% confidence interval, 0.87-1.00) and 0.77 (95% confidence interval, 0.52-1.00), respectively. Conclusions Uveal Melanoma is rare in children or teenagers. It occurs in a heterogeneous group displaying various associations, especially with oculo(dermal) melanocytosis. Oculo(dermal) melanocytosis is 9 times (95% confidence interval, 3.6-22.8) more common in young patients with Uveal Melanoma than in the general population with Uveal Melanoma. Young patients with Uveal Melanoma have short-term (5-year) survival better than that of adults, but the long-term (15-year) survival is similar to that of adults.

  • lifetime prevalence of Uveal Melanoma in white patients with oculo dermal melanocytosis
    Ophthalmology, 1998
    Co-Authors: Arun D. Singh, Carol L. Shields, Patrick De Potter, Jerry A. Shields, Bonnie A. Fijal, Robert C. Elston
    Abstract:

    Objective: In the white population, an association between oculo(dermal) melanocytosis (ODM) and Uveal Melanoma is well recognized. However, the lifetime prevalence of Uveal Melanoma in the ODM population is not known. This study was designed to determine the lifetime prevalence of Uveal Melanoma among patients with ocular melanocytosis. Design: Fifty-six white patients manifesting ODM with Uveal Melanoma formed the basis of the study. Main Outcome Measures: Published prevalence rates of ODM and Uveal Melanoma were used for calculations using Bayes' theorem. Results: The lifetime prevalence of Uveal Melanoma in white patients with ODM is estimated to be 2.6 × 10 −3 . The median age at diagnosis of Uveal Melanoma in the ODM population was similar to a randomly selected population (60.5 years and 62.5 years, respectively). In the vast majority of patients (90%) with ODM-associated Uveal Melanoma, the Uveal Melanoma was diagnosed between the ages of 31 years and 80 years. Conclusions: One of about 400 patients with ODM followed for life is estimated to develop Uveal Melanoma. Excessive melanocytes in the Uveal tract in ODM may provide the biologic basis for susceptibility to the development of Uveal Melanoma. Patients with ODM should be monitored ophthalmoscopically, especially during the susceptible period, for the development of Uveal Melanoma. The authors suggest that a national registry of ODM patients be created and prospective data collected to better assess the risk of developing Uveal Melanoma.

  • Genetic aspects of Uveal Melanoma: a brief review.
    Seminars in Oncology, 1996
    Co-Authors: Arun D. Singh, Larry A. Donoso, Carol L. Shields, M. X. Wang, P. De Potter, Jerry A. Shields
    Abstract:

    Uveal Melanoma usually occurs sporadically in the absence of obvious genetic predisposing factors. However, in rare patients, there is a suggestion that there may be genetic predisposition. Rare occurrences of familial Uveal Melanoma are believed to be inherited in an autosomal dominant mode. There are a few clinical conditions that can predispose to or be associated with Uveal Melanoma, including ocular melanocytosis, neurofibromatosis type I, and familial atypical mole and Melanoma syndrome. Nonrandom cytogenetic changes in Uveal Melanoma are characterized by monosomy 3, trisomy 8, and structural or numerical abnormalities of chromosome 6. Alterations of chromosome 9p are less frequently observed. CDKN2 gene, a cutaneous Melanoma predisposition gene, is probably not a Uveal Melanoma predisposition gene as evidenced by the lack of somatic mutations involving this gene in Uveal Melanoma samples and the absence of germline mutations in familial Uveal Melanoma patients. Transgenic mouse models developed using a tyrosinase promoter tagged with a mutated ras gene or SV40-Tag oncoprotein develop retinal pigment epithelium tumors that resemble Uveal Melanoma. We propose that Uveal Melanoma cases be categorized on genetic basis according to a new classification system. This classification scheme will help to identify and uniformly categorize Uveal Melanoma patients with genetic predisposition. Such patients offer unique opportunities for studying the genetic aspects of Uveal Melanoma and, therefore, appropriate tissue samples should be obtained from them for molecular genetic studies. Further studies are needed to fully understand the genetic aspects of Uveal Melanoma.

Martine J. Jager - One of the best experts on this subject based on the ideXlab platform.

  • Uveal Melanoma: Towards a molecular understanding.
    Progress in retinal and eye research, 2019
    Co-Authors: Kyra N. Smit, Martine J. Jager, Annelies De Klein, Emine Kiliҫ
    Abstract:

    Uveal Melanoma is an aggressive malignancy that originates from melanocytes in the eye. Even if the primary tumor has been successfully treated with radiation or surgery, up to half of all UM patients will eventually develop metastatic disease. Despite the common origin from neural crest-derived cells, Uveal and cutaneous Melanoma have few overlapping genetic signatures and Uveal Melanoma has been shown to have a lower mutational burden. As a consequence, many therapies that have proven effective in cutaneous Melanoma -such as immunotherapy- have little or no success in Uveal Melanoma. Several independent studies have recently identified the underlying genetic aberrancies in Uveal Melanoma, which allow improved tumor classification and prognostication of metastatic disease. In most cases, activating mutations in the Gα11/Q pathway drive Uveal Melanoma oncogenesis, whereas mutations in the BAP1, SF3B1 or EIF1AX genes predict progression towards metastasis. Intriguingly, the composition of chromosomal anomalies of chromosome 3, 6 and 8, shown to correlate with an adverse outcome, are distinctive in the BAP1mut, SF3B1mut and EIF1AXmut Uveal Melanoma subtypes. Expression profiling and epigenetic studies underline this subdivision in high-, intermediate-, or low-metastatic risk subgroups and suggest a different approach in the future towards prevention and/or treatment based on the specific mutation present in the tumor of the patients. In this review we discuss the current knowledge of the underlying genetic events that lead to Uveal Melanoma, their implication for the disease course and prognosis, as well as the therapeutic possibilities that arise from targeting these different aberrant pathways.

  • animal eye models for Uveal Melanoma
    Ocular Oncology and Pathology, 2015
    Co-Authors: Jinfeng Cao, Martine J. Jager
    Abstract:

    Animal models play an important role in understanding tumor growth and may be used to develop novel therapies against human malignancies. The significance of the results from animal experiments depends on the selection of the proper model. Many attempts have been made to create appropriate animal models for Uveal Melanoma and its characteristic metastatic behavior. One approach is to use transgenic animal models or to implant tumor cells. A variety of tumor types have been used for this purpose: tumor cells, such as Greene Melanoma, murine B16 Melanoma, and human Uveal Melanoma cells, may be implanted in the eyes of hamsters, rats, rabbits, and mice, among others. Various inoculation routes, including into the anterior chamber and posterior compartment, and retro-orbitally, have been applied to obtain tumor growth mimicking ocular Uveal Melanoma. However, when we choose animal models, we must be conscious of many disadvantages, such as variable tumor growth, or the need for immunosuppression in xenogeneic grafts. In this paper, we will discuss the various eye models.

  • Uveal Melanoma: The Inflammatory Microenvironment
    Journal of innate immunity, 2012
    Co-Authors: Inge H.g. Bronkhorst, Martine J. Jager
    Abstract:

    Uveal Melanoma is a highly malignant intraocular tumor with quite homogeneous tumor tissue and a diffuse leukocytic infiltration. In contrast with many other malignancies, the presence of infiltrating macrophages and T cells is associated with a poor prognosis rather than a good one. The clear link between inflammation and cancer in this malignancy provides a paradigm for macrophage plasticity and function. Macrophages in Uveal Melanoma have an M2-like phenotype and are associated with the loss of one specific chromosome - monosomy 3. The central players involved in this process and discussed in this review include macrophages, T lymphocytes, chemokines and cytokines, including the macrophage-attraction molecules. When a tumor acquires the ability to release significant amounts of macrophage-attraction molecules it causes the expansion of a population of myeloid immature cells that may not only help the tumor to suppress immune reactions but also aid in the construction of new blood vessels for tumor growth. A better understanding of the molecular basis of a local myelomonocytic cell population will bring a better understanding of the immunopathology of this disease and will lead to therapeutic interventions in Uveal Melanoma. This review focuses on the roles of the local inflammatory microenvironment in the development and progression of Uveal Melanoma.

  • Current Concepts in Uveal Melanoma - Current Concepts in Uveal Melanoma
    Developments in Ophthalmology, 2011
    Co-Authors: Martine J. Jager
    Abstract:

    Preface: Jager, M.J. Desjardins, L. Kivela, T. Damato, B.E. Diagnosis of Uveal Melanoma: Kivela, T. Treatment Selection for Uveal Melanoma: Damato, B.E. Ruthenium-106 Brachytherapy: Pe'er, J. Treatment of Uveal Melanoma by Accelerated Proton Beam: Desjardins, L. Lumbroso-Le Rouic, L. Levy-Gabriel, C. Cassoux, N. Dendale, R. Mazal, A. Delacroix, S. Sastre, X. Plancher, C. Asselain, B. Stereotactic Photon Beam Irradiation of Uveal Melanoma: Zehetmayer, M. Local Resection of Uveal Melanoma: Damato, B.E. Biopsies in Uveal Melanoma: Midena, E. Parrozzanl, R. Analysis of Intraocular Biopsies: Coupland, S.E. Antiangiogenic Therapy in Uveal Melanoma: el Filali, M. van der Velden, P.A. Luyten, G.P.M. Jager, M.J. Immunotherapy of Uveal Melanoma: Bosch, J.J. Genetic Determinants of Uveal Melanoma: Couturier, J. Saule, S. Therapeutic Options in Metastatic Uveal Melanoma: Mariani, P. Servois, V. Piperno-Neumann, S.

  • Anti-Angiogenic Therapy in Uveal Melanoma
    Developments in ophthalmology, 2011
    Co-Authors: Mariam El Filali, Pieter A. Van Der Velden, Gregorius P. M. Luyten, Martine J. Jager
    Abstract:

    For several decades, targeting of tumor-related vessels has been regarded as a potential anticancer therapy. Such anti-angiogenic therapy is based on the assumption that a tumor cannot grow beyond the limits of diffusion (about 1-2 mm) of oxygen and nutrients from capillaries, unless angiogenesis takes place. Vascular endothelial growth factor (VEGF) plays a key role in angiogenesis, regulating vasopermeability as well as the proliferation and migration of endothelial cells. In several types of cancer (colon carcinoma, soft tissue sarcomas and gastric cancer), serum VEGF levels are a marker for disease stage and an indicator of metastasis. VEGF levels are significantly elevated in Uveal Melanoma patients with metastatic disease compared to patients without metastases. Anti-angiogenic therapy, such as bevacizumab, is currently used for the treatment of metastases of several malignancies. Anti-angiogenic therapy has not yet been tested for the treatment of primary Uveal Melanoma or related metastatic disease. Clinicians, however, have a broad experience with anti-angiogenic agents in patients with Uveal Melanoma by treating the complications of radiation therapy. We will discuss tumor angiogenic processes and related molecular pathways in Uveal Melanoma. The role of VEGF and the potential use of current commercially and experimentally available anti-angiogenic drugs for the treatment of primary Uveal Melanoma and/or metastatic disease will be explained below.

Carol L. Shields - One of the best experts on this subject based on the ideXlab platform.

  • Uveal Melanoma: Estimating prognosis
    Wolters Kluwer Medknow Publications, 2015
    Co-Authors: Swathi Kaliki, Carol L. Shields, Jerry A. Shields
    Abstract:

    Uveal Melanoma is the most common primary malignant tumor of the eye in adults, predominantly found in Caucasians. Local tumor control of Uveal Melanoma is excellent, yet this malignancy is associated with relatively high mortality secondary to metastasis. Various clinical, histopathological, cytogenetic features and gene expression features help in estimating the prognosis of Uveal Melanoma. The clinical features associated with poor prognosis in patients with Uveal Melanoma include older age at presentation, male gender, larger tumor basal diameter and thickness, ciliary body location, diffuse tumor configuration, association with ocular/oculodermal melanocytosis, extraocular tumor extension, and advanced tumor staging by American Joint Committee on Cancer classification. Histopathological features suggestive of poor prognosis include epithelioid cell type, high mitotic activity, higher values of mean diameter of ten largest nucleoli, higher microvascular density, extravascular matrix patterns, tumor-infiltrating lymphocytes, tumor-infiltrating macrophages, higher expression of insulin-like growth factor-1 receptor, and higher expression of human leukocyte antigen Class I and II. Monosomy 3, 1p loss, 6q loss, and 8q and those classified as Class II by gene expression are predictive of poor prognosis of Uveal Melanoma. In this review, we discuss the prognostic factors of Uveal Melanoma. A database search was performed on PubMed, using the terms "uvea," "iris," "ciliary body," "choroid," "Melanoma," "Uveal Melanoma" and "prognosis," "metastasis," "genetic testing," "gene expression profiling." Relevant English language articles were extracted, reviewed, and referenced appropriately

  • Overview of Management of Posterior Uveal Melanoma
    Radiotherapy of Intraocular and Orbital Tumors, 2003
    Co-Authors: Jerry A. Shields, Carol L. Shields, Luther W. Brady, Bizhan Micaily
    Abstract:

    In the first edition of this textbook, we stressed the controversies in management of Melanomas of the ciliary body and choroid (posterior Uveal Melanoma). Many of the controversies have been largely resolved, and there continue to be new developments related to the management of patients with posterior Uveal Melanoma. Therefore, it seems appropriate in this chapter to provide a brief overview of the current options in management of this important intraocular tumor. Other authors will discuss the details of radiation therapy of Uveal Melanoma.

  • Uveal Melanoma in young patients.
    Archives of ophthalmology (Chicago Ill. : 1960), 2000
    Co-Authors: Arun D. Singh, Carol L. Shields, Jerry A. Shields, Takami Sato
    Abstract:

    Objective To study the clinical profile of young patients with Uveal Melanoma. Design Retrospective case-control series. Setting Tertiary referral center. Patients Data on 63 patients aged 20 years or younger with Uveal Melanoma were reviewed for clinical profile and association with oculo(dermal) melanocytosis, familial Uveal Melanoma, dysplastic nevus syndrome, cutaneous Melanoma, and other second malignant neoplasms. Results Of 8000 patients with Uveal Melanoma, 63 (0.8%) were found in patients who were 20 years of age or younger. The median age at diagnosis was 16 years, and the youngest patient was 3 years old. Sixty-two patients (98%) were white, and Uveal Melanoma was unilateral in all cases. Seven patients (11%) had oculo(dermal) melanocytosis. Two patients (3%) had dysplastic nevi syndrome, and personal history of cutaneous Melanoma was observed in 1 patient (2%). No other second cancers were present in any patient. The 5- and 15-year posttreatment survival estimates were 0.95 (95% confidence interval, 0.87-1.00) and 0.77 (95% confidence interval, 0.52-1.00), respectively. Conclusions Uveal Melanoma is rare in children or teenagers. It occurs in a heterogeneous group displaying various associations, especially with oculo(dermal) melanocytosis. Oculo(dermal) melanocytosis is 9 times (95% confidence interval, 3.6-22.8) more common in young patients with Uveal Melanoma than in the general population with Uveal Melanoma. Young patients with Uveal Melanoma have short-term (5-year) survival better than that of adults, but the long-term (15-year) survival is similar to that of adults.

  • lifetime prevalence of Uveal Melanoma in white patients with oculo dermal melanocytosis
    Ophthalmology, 1998
    Co-Authors: Arun D. Singh, Carol L. Shields, Patrick De Potter, Jerry A. Shields, Bonnie A. Fijal, Robert C. Elston
    Abstract:

    Objective: In the white population, an association between oculo(dermal) melanocytosis (ODM) and Uveal Melanoma is well recognized. However, the lifetime prevalence of Uveal Melanoma in the ODM population is not known. This study was designed to determine the lifetime prevalence of Uveal Melanoma among patients with ocular melanocytosis. Design: Fifty-six white patients manifesting ODM with Uveal Melanoma formed the basis of the study. Main Outcome Measures: Published prevalence rates of ODM and Uveal Melanoma were used for calculations using Bayes' theorem. Results: The lifetime prevalence of Uveal Melanoma in white patients with ODM is estimated to be 2.6 × 10 −3 . The median age at diagnosis of Uveal Melanoma in the ODM population was similar to a randomly selected population (60.5 years and 62.5 years, respectively). In the vast majority of patients (90%) with ODM-associated Uveal Melanoma, the Uveal Melanoma was diagnosed between the ages of 31 years and 80 years. Conclusions: One of about 400 patients with ODM followed for life is estimated to develop Uveal Melanoma. Excessive melanocytes in the Uveal tract in ODM may provide the biologic basis for susceptibility to the development of Uveal Melanoma. Patients with ODM should be monitored ophthalmoscopically, especially during the susceptible period, for the development of Uveal Melanoma. The authors suggest that a national registry of ODM patients be created and prospective data collected to better assess the risk of developing Uveal Melanoma.

  • Genetic aspects of Uveal Melanoma: a brief review.
    Seminars in Oncology, 1996
    Co-Authors: Arun D. Singh, Larry A. Donoso, Carol L. Shields, M. X. Wang, P. De Potter, Jerry A. Shields
    Abstract:

    Uveal Melanoma usually occurs sporadically in the absence of obvious genetic predisposing factors. However, in rare patients, there is a suggestion that there may be genetic predisposition. Rare occurrences of familial Uveal Melanoma are believed to be inherited in an autosomal dominant mode. There are a few clinical conditions that can predispose to or be associated with Uveal Melanoma, including ocular melanocytosis, neurofibromatosis type I, and familial atypical mole and Melanoma syndrome. Nonrandom cytogenetic changes in Uveal Melanoma are characterized by monosomy 3, trisomy 8, and structural or numerical abnormalities of chromosome 6. Alterations of chromosome 9p are less frequently observed. CDKN2 gene, a cutaneous Melanoma predisposition gene, is probably not a Uveal Melanoma predisposition gene as evidenced by the lack of somatic mutations involving this gene in Uveal Melanoma samples and the absence of germline mutations in familial Uveal Melanoma patients. Transgenic mouse models developed using a tyrosinase promoter tagged with a mutated ras gene or SV40-Tag oncoprotein develop retinal pigment epithelium tumors that resemble Uveal Melanoma. We propose that Uveal Melanoma cases be categorized on genetic basis according to a new classification system. This classification scheme will help to identify and uniformly categorize Uveal Melanoma patients with genetic predisposition. Such patients offer unique opportunities for studying the genetic aspects of Uveal Melanoma and, therefore, appropriate tissue samples should be obtained from them for molecular genetic studies. Further studies are needed to fully understand the genetic aspects of Uveal Melanoma.

Klaus G Griewank - One of the best experts on this subject based on the ideXlab platform.

  • Is there a role for immune checkpoint blockade in metastatic Uveal Melanoma
    Journal of Translational Medicine, 2015
    Co-Authors: Bastian Schilling, Antje Sucker, Tim Schneider, Inga Möller, Annette Paschen, Dirk Schadendorf, Klaus G Griewank
    Abstract:

    Uveal Melanoma is the most common intraocular malignancy in adults with a disease specific mortality rate of ~40%. Oncogenic mutations in GNAQ and GNA11 were recently identified as driver mutations in ~90% of Uveal Melanoma. While localized disease can be effectively treated by surgery or radiotherapy, treatment options for metastatic Uveal Melanoma are limited. To investigate the interplay between Uveal Melanoma and the hosts´ immune system and to test immunotherapeutic approaches, we have established an syngenic mouse model of GNAQ oncogene-driven Melanoma.

  • Genetic and clinico-pathologic analysis of metastatic Uveal Melanoma
    Modern Pathology, 2014
    Co-Authors: Klaus G Griewank, Antje Sucker, Bastian Schilling, Johannes Van De Nes, Iris Moll, Hojabr Kakavand, Lauren E Haydu, Marina Asher, Lisa Zimmer, Uwe Hillen
    Abstract:

    Uveal Melanoma is the most common malignant tumor of the adult eye. Fifty percent of tumors will eventually metastasize, and there are no effective treatments for them. Recent studies of Uveal Melanoma have identified activating mutations in GNAQ and GNA11 , loss-of-function mutations in the tumor suppressor gene BAP1 , and recurrent mutations in codon 625 of SF3B1 . Previous studies have reported the existence of a higher frequency of GNA11 than GNAQ mutations, frequent BAP1 loss, and rare SF3B1 mutations in metastatic Uveal Melanoma. We analyzed a cohort of 30 Uveal Melanoma metastases for the occurrence of GNAQ , GNA11 , and SF3B1 mutations, as well as BAP1 loss, and correlated these parameters with clinical and histopathologic features. Most (92%) tumors were composed of cells with an epithelioid or mixed (

  • Pathology and genetics of Uveal Melanoma
    Pathology, 2013
    Co-Authors: Klaus G Griewank, Rajmohan Murali
    Abstract:

    Summary Uveal Melanoma is the most common malignant tumour of the adult eye. Around half of all Uveal Melanoma patients will eventually die of their disease. There are a number of effective options to treat the primary tumour locally, but once the tumour has metastasised, there are no curative therapies. Traditionally, the diagnosis of Uveal Melanoma and prognostic prediction was based solely on the clinical presentation and detailed histopathological evaluation. Recent genetic findings have shed light on the biology of these tumours, and led to the development of genetic tests that can help assess their malignant potential and prognosis. The genes, proteins and pathways that have been (and continue to be) discovered will likely result in novel targeted therapeutic approaches with high efficacy and low toxicity. In this review, we summarise the clinical, pathological and genetic features of Uveal Melanoma, with emphasis on recent discoveries.

  • genetic and molecular characterization of Uveal Melanoma cell lines
    Pigment Cell & Melanoma Research, 2012
    Co-Authors: Klaus G Griewank, Jahan S Khalili, Mert Sozen, Katherine Stempkehale, Chantale Bernatchez, Seth Wardell, Boris C Bastian, Scott E Woodman
    Abstract:

    Summary The recent identification of frequent activating mutations in GNAQ or GNA11 in Uveal Melanoma provides an opportunity to better understand the pathogenesis of this Melanoma subtype, and to develop rational therapeutics to target the cellular effects mediated by these mutations. Cell lines from Uveal Melanoma tumors are an essential tool for these types of analyses. We report the mutation status of relevant Melanoma genes, expression levels of proteins of interest and DNA fingerprinting of a panel of Uveal Melanoma cell lines used in the research community.

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