Germline testing for uveal melanoma
Reviewed by Ian Reekie

The authors present a study of 114 consecutive patients presenting with uveal melanoma. Between 1 December 2019 and 1 November 2021 all patients over 18-years-old presenting to their centre with uveal melanoma were offered germline testing for variants in BAP1, CDKN2A, CDK4, POT1 and MITF (December 2019-November 2021), MC1R (December 2019-April 2021) and BRCA2 and PTEN (April 2021-November 2021). Testing was initiated by the ocular oncologist, with support in discussing the results from a geneticist. The article concentrates on BAP1 germline mutation, as variants in this gene have a definite association with uveal melanoma. The authors found that 4/114 (3.5%) of patients with uveal melanoma had germline mutations in BAP1, which is in keeping with the rate found in other studies. Variants of unknown significance were detected in four other genes in 13.2% of patients. Patients with germline mutations in BAP1 were significantly more likely to have metastatic disease, and to have a family history of malignant mesothelioma. There was a non-significant trend towards a younger age of diagnosis of uveal melanoma in the germline mutation group. There were no significant differences in tumour site or size between the group with germline mutation vs. no germline mutations, nor differences in ultrasonographic characteristics, clinical appearance or the presence of subretinal fluid. The authors suggest that the results show the suitability of a model where ocular oncologists request BAP1 germline mutation screening in uveal melanoma patients. However, before this were to be rolled out further studies would be advisable, in particular examining the cost-effectiveness of this screening program, and also to ascertain the optimal management of patients’ relatives found to have germline mutations in BAP1 but who have not developed a uveal melanoma. Should these patients be followed up? By whom and how regularly? By what modality? Germline testing means we are not simply managing one patient, but whole families at a time.

Oncologist-led germline genetic testing for uveal melanoma.
Gillies B, Krema H, Chao A, et al.
OPHTHALMIC GENETICS
2023;44(3):253-61.