Genetics and RNA Regulation of Uveal Melanoma
by
, , , , and
Cristina Barbagallo
1,
Michele Stella
1,
Giuseppe Broggi
2
,
Andrea Russo
3
,
Rosario Caltabiano
2
and
Marco Ragusa
1,*
1
Department of Biomedical and Biotechnological Sciences—Section of Biology and Genetics, University of Catania, 95123 Catania, Italy
2
Department of Medical, Surgical Sciences and Advanced Technologies G.F. Ingrassia—Section of Anatomic Pathology, University of Catania, 95123 Catania, Italy
3
Department of Ophthalmology, University of Catania, 95123 Catania, Italy
*
Author to whom correspondence should be addressed.
Cancers 2023, 15(3), 775; https://doi.org/10.3390/cancers15030775
Submission received: 30 December 2022
/
Revised: 20 January 2023
/
Accepted: 23 January 2023
/
Published: 26 January 2023
(This article belongs to the Special Issue Epidemiology and Biological Features of Melanoma)
Simple Summary
Uveal melanoma (UM) is a rare eye cancer with a high mortality rate due to metastases, leading to death in up to 50% of patients within 10 years from UM diagnosis. Moreover, patients show a median survival of 6 to 12 months after metastasis diagnosis. UM and cutaneous melanoma (CM) have the same melanocytic origin; however, they are very different in terms of molecular alterations and biological behavior. In this review, we will discuss the complex genetic and non-coding RNA-based epigenetic landscapes underlying the transformation, progression, and dissemination of UM. This knowledge will pave the way for the future identification of new biomarkers of the pathology and therapeutic targets.
Abstract
Uveal melanoma (UM) is the most common intraocular malignant tumor and the most frequent melanoma not affecting the skin. While the rate of UM occurrence is relatively low, about 50% of patients develop metastasis, primarily to the liver, with lethal outcome despite medical treatment. Notwithstanding that UM etiopathogenesis is still under investigation, a set of known mutations and chromosomal aberrations are associated with its pathogenesis and have a relevant prognostic value. The most frequently mutated genes are BAP1, EIF1AX, GNA11, GNAQ, and SF3B1, with mutually exclusive mutations occurring in GNAQ and GNA11, and almost mutually exclusive ones in BAP1 and SF3B1, and BAP1 and EIF1AX. Among chromosomal aberrations, monosomy of chromosome 3 is the most frequent, followed by gain of chromosome 8q, and full or partial loss of chromosomes 1 and 6. In addition, epigenetic mechanisms regulated by non-coding RNAs (ncRNA), namely microRNAs and long non-coding RNAs, have also been investigated. Several papers investigating the role of ncRNAs in UM have reported that their dysregulated expression affects cancer-related processes in both in vitro and in vivo models. This review will summarize current findings about genetic mutations, chromosomal aberrations, and ncRNA dysregulation establishing UM biology.
