BRAF mutations are detectable in conjunctival but not uveal melanomas

Spendlove, Hayley E.; Damato, Bertil; Humphreys, Jane; Barker, Karen; Hiscott, Paul; Houlston, Richard S.

doi:10.1097/00008390-200412000-00003

Cited by 108 publications

(76 citation statements)

References 20 publications

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“…These mutations have been shown to be present in 66 to 80% of cutaneous melanomas and have also been detected in up to 82% of melanocytic nevi (Pollock et al, 2003). The mutation has also been reported in 22-40% of conjunctival melanomas and recently our group has identified this mutation in 48% of 19 iris melanomas (Gear et al, 2004;Spendlove et al, 2004;Henriquez et al, 2007). However, there have been several studies, in uveal melanoma including primary and metastatic choroidal and ciliary body melanomas and the BRAF mutation has only been identified in one case (Malaponte et al, 2006).…”

Section: Discussionmentioning

confidence: 75%

The T1799A point mutation is present in posterior uveal melanoma

et al. 2008

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An activating mutation in exon 15 of the BRAF gene is present in a high proportion of cutaneous pigmented lesions. Until recently this mutation had however only been identified in one case of posterior uveal melanoma. Despite this apparent lack of the BRAF mutation, inappropriate downstream activation of the Ras/Raf/MAPK pathway has been described in posterior uveal melanoma. Based on the already recognised morphological and cytogenetic heterogeneity in uveal melanoma, we hypothesised that the BRAF mutation may be present in uveal melanoma but only in some of the tumour cells. In this study, we analysed 20 ciliary body and 30 choroidal melanomas using a nested PCR-based technique resulting in the amplification of a nested product only if the mutation was present. This sensitive technique can identify mutated DNA in the presence of wild-type DNA. The mutation was identified in 4 of 20 (20%) ciliary body and 11 of 30 (40%) choroidal melanomas. Further analysis of separate areas within the same choroidal melanoma demonstrated that the mutation was not present in the entire tumour. In conclusion, the T1799A BRAF mutation is present in a proportion of posterior uveal melanomas but within these tumours the distribution of the mutation is heterogeneous.

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Section: Discussionmentioning

confidence: 75%

The T1799A point mutation is present in posterior uveal melanoma

et al. 2008

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“…The majority of cutaneous melanomas occur in areas exposed to sun radiation, whereas the majority of uveal melanomas occur in the posterior segment of the eye, which is not exposed to significant sun radiation. Chromosomal assessment and molecular biological and epidemiological studies demonstrate that cutaneous melanomas differ from uveal melanomas (29)(30)(31)(32)(33)(34), whereas conjunctival melanomas appear to have more similarities to cutaneous than uveal melanomas (32,34). The primary underlying biological differences between uveal and cutaneous melanomas may be associated with various gene mutations and differing microenvironments.…”

Section: Discussionmentioning

confidence: 99%

Chrysin induces cell apoptosis in human uveal melanoma cells via intrinsic apoptosis

Xue

Chen

et al. 2016

Oncology Letters

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Abstract. Uveal melanoma is the most common intraocular malignant tumor in adults. Chrysin is a flavonoid present in honey, propolis, various plants and herbs. In the present study, the cytotoxic effects of chrysin were investigated on human uveal melanoma cell lines (M17 and SP6.5) and associated signaling pathways, and a comparison to the effects on normal ocular cells [scleral fibroblasts and retinal pigment epithelial (RPE) cells] was performed. The effects of chrysin on cell viability were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell apoptosis was determined by using terminal deoxynucleotidyl transferase mediated dUTP nick end-labeling assay. Mitochondrial permeability was determined by JC-1 fluorescein analysis. Cytosol cytochrome c levels, and the activities of caspase-3, -8 and -9 were measured by enzyme-linked immunosorbent assay or colorimetric assay. Chrysin reduced the viability of cultured human melanoma cells in a dose-dependent manner (0, 10, 30 and 100 µM) with IC 50 at 28.3 and 35.8 µM in SP6.5 and M17 cell lines, respectively. Chrysin at 30-100 µM levels selectively reduced the viability of melanoma cells without affecting the viability of scleral fibroblasts and RPE cells. Chrysin increased mitochondrial permeability, the levels of cytosol cytochrome c, and caspase-9 and -3 activities, but not capase-8 activity in uveal melanoma cells. The results of the present study indicate that chrysin induces apoptosis of human uveal melanoma cells via the mitochondrial signaling pathway and suggest that chrysin may be a promising agent in the treatment of uveal melanoma.

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“…1,23,25,27,42 Genetic abnormalities of CoM CoMs show mutation of BRAF (7q34). 45,46,[49][50][51][52]55 This gene encodes a serine/threonine kinase in the 45 We now test all CoMs routinely for the BRAF V600E mutation, which may predict responsiveness to Vemurafenib should the patient develop metastatic disease. 56 We have also demonstrated that primary CoM showed amplification of CDKN1A and RUNX2 (both 6p21.2); in metastatic CoM, MLH1 (3p22.1) and TIMP2 (17q25.3) were frequently amplified, and MGMT (20q26.3) and ECHS1 (10q26.3) were frequently deleted.…”

Section: Prognosismentioning

confidence: 99%