Role of somatic mutations and chromosomal aberrations in the prognosis of uveal melanoma in a Spanish patient cohort

Abstract

Background: Uveal melanoma (UM) has a high tendency to cause liver metastases. Metastatic disease is fatal, with a low survival rate. There are two large groups of UMs that, according to their risk of metastatic disease, can be divided into risk subgroups based on histopathological, cytogenetic and molecular characteristics. The presence of somatic mutations in certain genes may explain the origin and prognosis of these tumours.

Methods: Forty-six UM samples previously classified as high or low metastatic risk according to chromosome 3 copy number status were tested for somatic mutations. A multi-gene targeting strategy was adopted, and sequencing was performed using AmpliSeq technology.

Results: Mutations were found in all major UM-related genes. BAP1 mutations confer an increased risk of metastases in high-risk tumours; thus, this gene acts as a strong prognostic predictor in UM. The presence of somatic mutations in LZTS1 did not show significant differences in the risk of metastases.

Conclusions: This result supports the idea that exploring mutations and copy number variations in UM provides insights into patient outcomes. Genetic tests allow the determination of accurate personalized molecular profiles with a fundamental prognostic purpose.

Keywords: BAP1; genetics; prognosis; somatic mutations; uveal melanoma.