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Background:Uveal melanoma is the most frequent primary tumour of the eye. It is molecularly clearly distinct from cutaneous melanoma and shows a different pattern of driver mutations. The influence of sunlight ultraviolet (UV) exposure on the aetiology of uveal melanoma is a matter of debate. The recent identification of driver mutations in the promoter of the telomerase reverse transcriptase (TERT) gene with UV-induced cytidine-to-thymidine transitions in cutaneous melanoma prompted us to investigate whether these mutations also occur in uveal melanoma.Methods:We analysed 50 cases of uveal melanoma obtained from enucleation surgery for mutations in the genes GNAQ, GNA11, BAP1, SF3B1, EIFAX1 and TERT, measured gene expression using microarrays and analysed gene copy numbers by SNP arrays.Results:We detected a TERT mutation in only one case of a 57-year-old white male patient with clinical and histopathological features typical for uveal melanoma. The tumour showed mutations in GNA11 and EIF1AX that are typical for uveal melanoma and absent from cutaneous melanoma. No mutations were detected in GNAQ, BAP1 and SF3B1 that are frequently mutated in uveal melanoma. Both copies of chromosome 3 were retained. Several tumours among which the one carrying the TERT promoter mutation showed elevated TERT expression. Consistent with previous reports, GNAQ is inversely associated with chromosome 3 monosomy and metastasis. BAP1 mutations are significantly associated with chromosome 3 monosomy but not with relapse.Conclusion:These data indicate that TERT mutations are rare in uveal melanoma. No conclusion can be drawn on their potential influence on tumour progression. [ABSTRACT FROM AUTHOR]

Purpose Around 10 centers worldwide treat ocular tumors with proton therapy, all with dedicated eyelines. Our synchrotron-based facility is equipped with general-purpose fixed beamlines; proton and carbon ion treatments are delivered with pencil beam scanning modality (range in water 3 ÷ 32 cm). Recently, our proton beamline was adapted to treat also ocular diseases. The main dosimetric properties of this new eyeline are described in this work. Methods A 3 cm water-equivalent range shifter (RS) was placed along the beamline to reach shallower penetration depths. In order to achieve steep lateral dose gradients, the position of the RS and patient-specific collimator were simulated using MonteCarlo (MC) FLUKA code. Lateral dose profiles were measured with gafchromic EBT3 films to evaluate lateral penumbra width and dose homogeneity. Several beam scanning patterns were tested. Depth-dose distributions (DDDs) were measured with the Peakfinder system. To obtain uniform dose distributions (Spread-Out Bragg Peaks, SOBPs), the weights of each DDD were optimized simulating different targets. Absorbed doses were then measured in water with an advanced Markus chamber. Neutron dose at the contralateral eye was also evaluated with passive bubble dosimeters. Results MC simulations and experimental results showed that maximizing the distance between RS and collimator reduces the lateral dose penumbra of the collimated beam and increases field transversal dose homogeneity. Therefore, RS and patient-specific collimator were placed at about 98 cm (behind beam monitors) and 6 cm from the isocenter, respectively. The lateral penumbra (distal fall-off) ranged between 1.0 and 1.8 mm (1.0 and 1.6 mm). The measured SOBP doses were in very good agreement with MC simulations, as shown in Fig. 1. The mean neutron dose at the contralateral eye was 68.8 ± 10.2 μSv/Gy. Conclusions Our eyeline satisfied the requirements to treat ocular tumors. The first ocular patient was treated in August 2016. Around 60 patients have been treated so far. [ABSTRACT FROM AUTHOR]