GNAQ and GNA11 Genes: A Comprehensive Review on Oncogenesis, Prognosis and Therapeutic Opportunities in Uveal Melanoma.

The GNAQ and GNA11 genes are mutated in almost 80-90% of uveal melanomas in a mutually exclusive pattern. These genes encode the alpha subunits of the heterotrimeric G proteins, Gq and G11; thus, mutations of these genes result in the activation of several important signaling pathways, including phospholipase C, and activation of the transcription factor YAP. It is well known that both of them act as driver genes in the oncogenic process and it has been assumed that they do not play a role in the prognosis of these tumours. However, it has been hypothesised that mutations in these genes could give rise to molecularly and clinically distinct types of uveal melanomas. It has also been questioned whether the type and location of mutation in the GNAQ and GNA11 genes may affect the progression of these tumours. All of these questions, except for their implications in carcinogenesis, remain controversial. Uveal melanoma has a distinctive genetic profile, and specific recurrent mutations, which make it a potential candidate for treatment with targeted therapy. Given that the most frequent mutations are those observed in the GNAQ and GNA11 genes, and that both genes are involved in oncogenesis, these molecules, as well as the downstream signalling pathways in which they are involved, have been proposed as promising potential therapeutic targets. Therefore, in this review, special attention is paid to the current data related to the possible prognostic implications of both genes from different perspectives, as well as the therapeutic options targeting them.

Applications of Non-Coding RNAs in Patients With Retinoblastoma.

Retinoblastoma (RB) is the most common primary intraocular malignancy in childhood. In the carcinogenic process of neoplasms such as RB, the role of non-coding RNAs (ncRNAs) has been widely demonstrated recently. In this review, we aim to provide a clinical overview of the current knowledge regarding ncRNAs in relation to RB. Although ncRNAs are now considered as potential diagnostic biomarkers, prognostic factors, and therapeutic targets, further studies will facilitate enhanced understanding of ncRNAs in RB physiopathology and define the roles ncRNAs can play in clinical practice.

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

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.

The Role of Non-Coding RNAs in Uveal Melanoma.

Uveal melanoma (UM) is the most common primary intraocular tumor in adulthood. Approximately 50% of patients develop metastatic disease, which typically affects the liver and is usually fatal within one year. This type of cancer is heterogeneous in nature and is divided into two broad groups of tumors according to their susceptibility to develop metastasis. In the last decade, chromosomal abnormalities and the aberrant expression of several signaling pathways and oncogenes in uveal melanomas have been described. Recently, importance has been given to the association of the mentioned deregulation with the expression of non-coding RNAs (ncRNAs). Here, we review the different classes of ncRNAs-such as long non-coding RNAs (lncRNAs) and microRNAs (miRNAs)-and their contribution to the development of UM. Special attention is given to miRNAs and their regulatory role in physiopathology and their potential as biomarkers. As important agents in gene regulation, ncRNAs have a huge potential for opening up therapeutic pathways, predicting response to treatment, and anticipating patient outcome for UM.

Treatment of Metastatic Uveal Melanoma: Systematic Review.

INTRODUCTION: More than 50% of patients with uveal melanoma end up developing metastases. Currently, there is no standard first-line treatment that facilitates proper management of the metastatic disease. METHODS: A systematic review of the last 40 years in PubMed with an exhaustive and strict selection of studies was conducted, in which the unit of measurement was overall survival (OS) expressed in Kaplan-Meier curves or numerically. RESULTS: After the selection process, 110 articles were included. Regional therapies, such as intra-arterial liver chemotherapy (OS: 2, 9-22 months), isolated liver perfusion (OS: 9, 6-27, 4 months), or selective internal radiation therapy (OS: 18 months in monotherapy and 26 months in combination with other therapies) showed some superiority when compared to systemic therapies, such as chemotherapy (OS: 4, 6-17 months), immunotherapy (OS: 5-19, 1 month), immunosuppression (OS: 11 months), or targeted therapy (OS: 6-12 months), without being significant. CONCLUSIONS: The results of this review suggest that there are no important differences in OS when comparing the different current treatment modalities. Most of the differences found seem to be explained by the heterogenicity of the different studies and the presence of biases in their design, rather than actual extensions of patient survival.