Genetic prognostication in uveal melanoma

Abstract

Uveal melanoma (UM) is a rare tumour with a high propensity to metastasize. Although no effective treatment for metastases yet exists, prognostication in UM is relevant for patient counselling, planning of follow-up and stratification in clinical trials. Besides conventional clinicopathologic characteristics, genetic tumour features with prognostic significance have been identified. Non-random chromosome aberrations such as monosomy 3 and gain of chromosome 8q are strongly correlated with metastatic risk, while gain of chromosome 6p indicates a low risk. Recently, mutations in genes such as BAP1, SF3B1 and EIF1AX have been shown to be related to patient outcome. Genetics of UM is a rapidly advancing field, which not only contributes to the understanding of the pathogenesis of this cancer, but also results in further refinement of prognostication. Concomitantly, advances have been made in the use of genetic tests. New methods for genetic typing of UM have been developed. Despite the considerable progress made recently, many questions remain, such as those relating to the reliability of prognostic genetic tests, and the use of biopsied or previously irradiated tumour tissue for prognostication by genetic testing. In this article, we review genetic prognostic indicators in UM, also comparing available genetic tests, addressing the clinical application of genetic prognostication and discussing future perspectives for improving genetic prognostication in UM.

Intraocular biopsy of uveal melanoma Risk assessment and identification of genetic prognostic markers

“…The use in clinical practice is limited by the cost, heavy laboratory work load and the need for an experienced cytogeneticist. In addition, the low resolution only allows for detection of gross chromosomal changes (Dogrusöz & Jager ).…”

“…In contrast, copy number analyses based on detection of single nucleotide polymorphisms (SNP array) or micro satellites (MSA) can differentiate between the allele inherited from the mother and father, respectively (Dogrusöz & Jager ).…”

ECCO essential requirements for quality cancer care for melanoma: Defining how to organise care

“…• Genetic analysis for prognostication by analysis of chromosomal aberrations (monosomy 3, extra copies of chromosome 8), expression arrays to determine class I or class I and/or BAP1 mutations must only be performed after informed consent of the patient (Dogrusözm and Jager, 2017). …”

Identification of differentially expressed genes and functional annotations associated with metastases of the uveal melanoma

“…Uveal melanoma (UVM), the most frequently occurring type of intraocular malignancy in adults, has a strong tendency to metastasize . UVMs account for the majority (85%) of ocular melanomas . Their average annual incidence in the United States is 5.1 × 10 −6 .…”

“…1 UVMs account for the majority (85%) of ocular melanomas. 2 Their average annual incidence in the United States is 5.1 × 10 −6 . 3 In Europe, the incidence reportedly increases with age, peaking at 75 years and then plateauing.…”