Technical innovations in liquid biopsies

Uveal melanoma is a rare and aggressive intraocular malignancy. The majority of diagnoses are made on the basis of clinical examination solely, without taking a tumour biopsy. As more patients are treated by local, eye‐preserving radiotherapy instead of an enucleation, tumour tissue becomes even less available for further analysis. Nevertheless, the molecular characterisation of a patient's primary uveal melanoma may yield clinically‐important information.

Over the past decades, prognostically‐relevant molecular tumour subtypes have been identified based on the genetic alterations present in a uveal melanoma. These subtypes present independently from established clinicopathological markers such as tumour diameter and prominence. Patients with an increased risk of metastatic dissemination may be offered a more intense follow‐up screening program, and could possibly benefit from earlier detection of metastasis. Additionally, knowledge about the molecular profile of the primary tumour has been positively associated with various aspects of psychosocial well‐being and might be of (future) clinical relevance with regard to novel (neo‐)adjuvant therapies.

Digital PCR is one of the most sensitive molecular technologies available to analyse solid and liquid biopsies from cancer patients. It is widely used in a variety of malignancies, and in different stages of disease. We developed novel assays and experimental setups to make this technology applicable in the context of uveal melanoma. These were validated and applied in primary and metastatic tumour specimens, and in vitreous fluid samples obtained from eyes with a uveal melanoma. Others used this technology for the analysis of blood from patients with primary or metastatic uveal melanoma.

In this talk, the challenges and opportunities of digital PCR in the context of uveal melanoma will be discussed, and compared to those of other technologies available in the field.