Our partners at the Institute Curie (Paris, France) have recently published in American Association for Cancer Research June issue a paper that explains the importance of genetic testing in the setting of metastatic UM, namely how it can help predict treatment responses. 

Influence of Tumour Genetic Testing in the treatment of Uveal Melanoma


Uveal Melanoma (UM), from a development perspective, is one of the simplest adult tumours. This means that, in terms of alterations that occur in cells that lead to tumour formation (ie. Genetic events), UM is rather limited. Nonetheless, how and when these alterations occur is still not fully understood.

Genetic events, also called mutations, in the UM setting, can be informative of prognosis (how aggressive the tumour might be) and can also predict treatment response.

Most genetic events that occur in uveal melanocytes that give rise to uveal melanoma, generate stable cells that are not detected by the immune system. This is one of the reasons why UM response to classic immunotherapy is limited (as opposed to cutaneous melanoma). Rarely, a mutation may occur at the level of MDB4, a gene responsible for repairing DNA damage. Contrary to other genetic events in UM, MDB4 mutations originate tumours that are more reactive with the immune system.

This study evaluated liver metastases of UM patients and studied ther genetic events. Dividing the tumours in term of MDB4 presence (the mutation makes it absent, allowing for more genetic events), MDB4 mutated tumours show a much higher mutation rate vs tumours without MDB4 mutation. This higher amount of mutations makes UM more identifiable by the immune system, which may explain the efficacity of immunotherapy in MDB4 mutated tumours.