Metastatic disease in uveal melanoma. Issue 5 (October 2015)

• Record Type: Journal Article
• Authors: Van Beek, Jackelien G.M.; Koopmans, Anna E.; Vaarwater, Jolanda; Verdijk, Rob M.; de Klein, Annelies; Naus, Nicole C.; Kiliç, Emine
• Is Part Of: Melanoma research. Volume 25:Issue 5(2015)
• Publication Date: 2015-10
• Subjects: Melanoma -- Periodicals; Melanoma -- Periodicals; Melanomen; 616.99477
• DOI: 10.1097/CMR.0000000000000176
• Languages: English
• ISSNs: 0960-8931

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <p>Mutation of <italic>SF3B1</italic> has been identified in low-grade uveal melanoma with a good prognosis. In this study, we compare chromosomal aberrations and gene mutations between a primary uveal melanoma and its multiple hepatic and peripancreatic metastases. DNA was isolated from a large primary uveal melanoma after fractionated stereotactic radiotherapy and three distinct metastases (two liver samples and one peripancreatic lymph node) to perform single-nucleotide polymorphism array and fluorescent in-situ hybridization. We analyzed mutations in uveal melanoma target genes <italic>BAP1</italic>, <italic>GNAQ</italic>, <italic>GNA11</italic>, <italic>SF3B1</italic>, and <italic>EIF1AX.</italic> The primary tumor showed no abnormalities in chromosome 3, whereas metastases showed deletion of at least 3q12.1-q24 and the <italic>BAP1</italic> gene was not mutated. All samples indicated the following consistent chromosomal aberrations: loss of 1p, gain of 6p, and gain of 8q. Subsequently, heterozygous <italic>SF3B1</italic> and heterozygous <italic>GNA11</italic> mutations were observed. The metastases showed more genetic aberrations than the primary tumor and may therefore represent the genetic status of the tumor before irradiation, whereas the current primary tumor shows presumably irradiation artifacts. An early occurring mutation in <italic>GNA11</italic> was observed in all samples. The <italic>SF3B1</italic> mutation seems to predispose for late metastatic disease in the absence of a <italic>BAP1</italic> mutation.</p> </sec> </abstract>