Genetic evidence for the role of ultraviolet radiation in the pathogenesis of uveal melanoma

Uveal melanoma (UM) is currently classified by the World Health Organisation as a melanoma caused by risk factors other than cumulative solar damage. However, factors relating to ultraviolet radiation (UVR) susceptibility such as light-coloured skin and eyes, propensity to burn, and proximity to the equator, frequently correlate with higher risk of UM. These risk factors echo those of the far more common cutaneous melanoma (CM), which is widely accepted to be caused by excessive UVR exposure, suggesting a role of UVR in the development and progression of a proportion of UM. Indeed, this could mean that countries, such as Australia, with high UVR exposure and the highest incidences of CM would represent a similarly high incidence of UM if UVR exposure is truly involved. Most cases of UM lack the typical genetic mutations that are related to UVR damage, although recent evidence in a small minority of cases has shown otherwise. This review therefore reassesses statistical, environmental, anatomical, and physiological evidence for and against the role of UVR in the aetiology of UM.

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Faculty Opinions recommendation of Genetic evidence for a role of BiP/Kar2 that regulates Ire1 in response to accumulation of unfolded proteins.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1014080.192856 ◽

2003 ◽

Author(s):

David Ron

Keyword(s):

Genetic Evidence ◽

Unfolded Proteins

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Histologic Findings of Choroidal Vasculopathy in Eyes Enucleated following Radiation Therapy for Uveal Melanoma: Radiation Choroidopathy

Klinische Monatsblätter für Augenheilkunde ◽

10.1055/a-1275-0626 ◽

2021 ◽

Author(s):

Sean Platt ◽

Diva R. Salomao ◽

Jose Pulido

Keyword(s):

Radiation Therapy ◽

Uveal Melanoma ◽

Malignant Tumors ◽

Vitreous Hemorrhage ◽

Radiation Retinopathy ◽

Radiation Induced ◽

Histopathologic Analysis ◽

Choroidal Vessels ◽

Choroidal Vasculopathy

Abstract Introduction Little has been published about the choroidal vascular changes that occur years after radiation exposure. The aim of this study was to review the histological changes observed in the choroidal vasculature following radiotherapy for uveal melanoma. Methods Records from a single institution were retrospectively reviewed from June 7, 2007 to June 7, 2017; 101 patients with a diagnosis of uveal melanoma that underwent enucleation had their records reviewed. Out of these, a total of 26 eyes had undergone plaque brachytherapy prior to enucleation, which had been performed at a mean time of 7.2 years (range from 0 years to 30 years) after the initial plaque placement. A histopathologic analysis was conducted on all 26 eyes with special emphasis on the choroidal changes. Of these 26 eyes, 18 demonstrated evidence of radiation-induced vasculopathy. Results Of the 18 eyes, 10/18 (55%) had radiation retinopathy and 16/18 (89%) had radiation choroidal vasculopathy. One patient had a phthisical eye, and the choroid could not be evaluated because the characteristics of the vasculature could not be determined. Nine cases had vitreous hemorrhage (50%), all cases had radiation retinopathy, and 8/9 (89%) had radiation choroidopathy. Of the 16 cases with radiation choroidal vasculopathy, 3/16 (19%) had only intratumoral radiation choroidal vasculopathy, 3/16 (19%) had only extratumoral radiation choroidal vasculopathy, and, thus, 10/16 (32%) had both intratumoral and extratumoral radiation choroidal vasculopathy. In patients with radiation choroidal vasculopathy, 2/16 (13%) had hyalinization of the choroidal vessels. Another 3/16 (19%) cases with radiation choroidal vasculopathy had ectatic vessels. The other 11/16 (68%) had evidence of both hyalinization of the choroidal vessels as well as ectatic vessels in the choroid. Histological evidence of radiation retinopathy and choroidopathy were seen in 69% of eyes enucleated after receiving radiation therapy, which, in some cases, also had vitreous hemorrhage. Polypoidal choroidal vasculopathy, choroidal neovascularization, and retinal choroidal anastomoses (RAP-type lesions) were seen in 12 of the 16 eyes (75%). Discussion/Conclusion Irradiation of malignant tumors of the eye causes not only radiation retinopathy but also radiation choroidopathy. The role of radiation choroidopathy in the subsequent visual loss following radiotherapy and the role of anti-VEGF therapy needs to be recognized and distinguished from radiation retinopathy. Our data adds to the prior limited knowledge that radiation affects the choroid and can induce specific phenotypes similar to the clinical spectrum of CNV, PCV, and RAP.

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Role of somatic mutations and chromosomal aberrations in the prognosis of uveal melanoma in a Spanish patient cohort

Acta Ophthalmologica ◽

10.1111/aos.14760 ◽

2021 ◽

Author(s):

Paula Silva‐Rodríguez ◽

Manuel Bande ◽

Daniel Fernández‐Díaz ◽

Nerea Lago‐Baameiro ◽

María Pardo ◽

...

Keyword(s):

Uveal Melanoma ◽

Chromosomal Aberrations ◽

Somatic Mutations ◽

Spanish Patient ◽

Patient Cohort

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Molecular Genetic Evidence for the Role of SGT1 in the Intramolecular Complementation of Bs2 Protein Activity in Nicotiana benthamiana

The Plant Cell ◽

10.1105/tpc.104.029637 ◽

2005 ◽

Vol 17 (4) ◽

pp. 1268-1278 ◽

Cited By ~ 81

Author(s):

R. Todd Leister ◽

Douglas Dahlbeck ◽

Brad Day ◽

Yi Li ◽

Olga Chesnokova ◽

...

Keyword(s):

Nicotiana Benthamiana ◽

Molecular Genetic ◽

Genetic Evidence ◽

Protein Activity ◽

Molecular Genetic Evidence

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Loss of Ubp3 increases silencing, decreases unequal recombination in rDNA, and shortens the replicative life span in Saccharomyces cerevisiae

Molecular Biology of the Cell ◽

10.1091/mbc.e13-10-0591 ◽

2014 ◽

Vol 25 (12) ◽

pp. 1916-1924 ◽

Cited By ~ 3

Author(s):

David Öling ◽

Rehan Masoom ◽

Kristian Kvint

Keyword(s):

Saccharomyces Cerevisiae ◽

Rna Polymerase ◽

Life Span ◽

Rna Polymerase Ii ◽

Ribosomal Dna ◽

Genetic Evidence ◽

Wild Type ◽

Replicative Life Span ◽

Unequal Recombination

Ubp3 is a conserved ubiquitin protease that acts as an antisilencing factor in MAT and telomeric regions. Here we show that ubp3∆ mutants also display increased silencing in ribosomal DNA (rDNA). Consistent with this, RNA polymerase II occupancy is lower in cells lacking Ubp3 than in wild-type cells in all heterochromatic regions. Moreover, in a ubp3∆ mutant, unequal recombination in rDNA is highly suppressed. We present genetic evidence that this effect on rDNA recombination, but not silencing, is entirely dependent on the silencing factor Sir2. Further, ubp3∆ sir2∆ mutants age prematurely at the same rate as sir2∆ mutants. Thus our data suggest that recombination negatively influences replicative life span more so than silencing. However, in ubp3∆ mutants, recombination is not a prerequisite for aging, since cells lacking Ubp3 have a shorter life span than isogenic wild-type cells. We discuss the data in view of different models on how silencing and unequal recombination affect replicative life span and the role of Ubp3 in these processes.

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Genetic Evidence for an Essential Role of Neuronally Expressed IL-6 Signal Transducer gp130 in the Induction and Maintenance of Experimentally Induced Mechanical Hypersensitivityin vivoandin vitro

Molecular Pain ◽

10.1186/1744-8069-7-73 ◽

2011 ◽

Vol 7 ◽

pp. 1744-8069-7-73 ◽

Cited By ~ 25

Author(s):

Serena Quarta ◽

Christian Vogl ◽

Cristina E Constantin ◽

Nurcan Üçeyler ◽

Claudia Sommer ◽

...

Keyword(s):

Essential Role ◽

Genetic Evidence ◽

Signal Transducer ◽

Experimentally Induced

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Ultraviolet Radiation and Chronic Inflammation—Molecules and Mechanisms Involved in Skin Carcinogenesis: A Narrative Review

Life ◽

10.3390/life11040326 ◽

2021 ◽

Vol 11 (4) ◽

pp. 326

Author(s):

Magdalena Ciążyńska ◽

Irmina Olejniczak-Staruch ◽

Dorota Sobolewska-Sztychny ◽

Joanna Narbutt ◽

Małgorzata Skibińska ◽

...

Keyword(s):

Ultraviolet Radiation ◽

Chronic Inflammation ◽

Potential Role ◽

Tumor Formation ◽

Skin Carcinogenesis ◽

Molecular Networks ◽

Cancer Therapies ◽

Inflammatory Microenvironment ◽

Skin Cancers

The process of skin carcinogenesis is still not fully understood. Both experimental and epidemiological evidence indicate that chronic inflammation is one of the hallmarks of microenvironmental-agent-mediated skin cancers and contributes to its development. Maintaining an inflammatory microenvironment is a condition leading to tumor formation. Multiple studies focus on the molecular pathways activating tumorigenesis by inflammation and indicate several biomarkers and factors that can improve diagnostic and prognostic processes in oncology and dermatology. Reactive oxygen species produced by ultraviolet radiation, oxidizers, or metabolic processes can damage cells and initiate pro-inflammatory cascades. Considering the potential role of inflammation in cancer development and metastasis, the identification of early mechanisms involved in carcinogenesis is crucial for clinical practice and scientific research. Moreover, it could lead to the progress of advanced skin cancer therapies. We focus on a comprehensive analysis of available evidence and on understanding how chronic inflammation and ultraviolet radiation can result in skin carcinogenesis. We present the inflammatory environment as complex molecular networks triggering tumorigenesis and constituting therapeutic targets.

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5-MOP Induced Protection Against Epidermal DNA Damage by Ultraviolet Radiation in Human Skin: The Role of the Skin Type

Light in Biology and Medicine ◽

10.1007/978-1-4684-5991-3_20 ◽

1991 ◽

pp. 201-209

Author(s):

Antony R. Young ◽

Christopher S. Potten ◽

Caroline A. Chadwick ◽

Gillian M. Murphy ◽

A. Jeffrey Cohen

Keyword(s):

Dna Damage ◽

Ultraviolet Radiation ◽

Human Skin ◽

Skin Type

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Disordered haematopoiesis and cardiovascular disease: a focus on myelopoiesis

Clinical Science ◽

10.1042/cs20180111 ◽

2018 ◽

Vol 132 (17) ◽

pp. 1889-1899 ◽

Cited By ~ 8

Author(s):

Dragana Dragoljevic ◽

Marit Westerterp ◽

Camilla Bertuzzo Veiga ◽

Prabhakara Nagareddy ◽

Andrew J. Murphy

Keyword(s):

Inflammatory Diseases ◽

Genetic Evidence ◽

Loss Of Function ◽

Atherosclerotic Vascular Disease ◽

Stem And Progenitor Cells ◽

Anti Inflammatory ◽

The Cantos ◽

Inflammatory Milieu ◽

Proliferative Advantage

Cardiovascular (CV) diseases (CVD) are primarily caused by atherosclerotic vascular disease. Atherogenesis is mainly driven by recruitment of leucocytes to the arterial wall, where macrophages contribute to both lipid retention as well as the inflammatory milieu within the vessel wall. Consequently, diseases which present with an enhanced abundance of circulating leucocytes, particularly monocytes, have also been documented to accelerate CVD. A host of metabolic and inflammatory diseases, such as obesity, diabetes, hypercholesteraemia, and rheumatoid arthritis (RA), have been shown to alter myelopoiesis to exacerbate atherosclerosis. Genetic evidence has emerged in humans with the discovery of clonal haematopoiesis of indeterminate potential (CHIP), resulting in a disordered haematopoietic system linked to accelerated atherogenesis. CHIP, caused by somatic mutations in haematopoietic stem and progenitor cells (HSPCs), consequently provide a proliferative advantage over native HSPCs and, in the case of Tet2 loss of function mutation, gives rise to inflammatory plaque macrophages (i.e. enhanced interleukin (IL)-1β production). Together with the recent findings of the CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcomes Study) trial that revealed blocking IL-1β using Canakinumab reduced CV events, these studies collectively have highlighted a pivotal role of IL-1β signalling in a population of people with atherosclerotic CVD. This review will explore how haematopoiesis is altered by risk-factors and inflammatory disorders that promote CVD. Further, we will discuss some of the recent genetic evidence of disordered haematopoiesis in relation to CVD though the association with CHIP and suggest that future studies should explore what initiates HSPC mutations, as well as how current anti-inflammatory agents affect CHIP-driven atherosclerosis.

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