Whole-genome copy-number analysis identifies new leads for chromosomal aberrations involved in the oncogenesis and metastastic behavior of uveal melanomas. Issue 3 (June 2015)

• Record Type: Journal Article
• Authors: van Engen-van Grunsven, Adriana C.H.; Baar, Marjolein P.; Pfundt, Rolph; Rijntjes, Jos; Küsters-Vandevelde, Heidi V.N.; Delbecq, Ann-Laure; Keunen, Jan E.; Klevering, Jeroen B.; Wesseling, Pieter; Blokx, Willeke A.M.; Groenen, Patricia J.T.A.
• Is Part Of: Melanoma research. Volume 25:Issue 3(2015)
• Publication Date: 2015-06
• Subjects: Melanoma -- Periodicals; Melanoma -- Periodicals; Melanomen; 616.99477
• DOI: 10.1097/CMR.0000000000000152
• Languages: English
• ISSNs: 0960-8931

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <p>To further elucidate the genetic underpinnings of uveal melanoma (UM) and identify new markers that correlate with disease outcome, archival formalin-fixed, paraffin-embedded enucleation specimens from 25 patients with UM and a mean follow-up of 14 years were analyzed for whole-genome copy-number alterations using OncoScan analysis. Copy-number alterations of chromosomes 1, 3, 6, and 8 were also analyzed in these tumors using multiplex ligation-dependent probe-amplification, and mutations in <italic>GNAQ</italic>, <italic>GNA11</italic>, and <italic>BAP1</italic> were searched for by Sanger sequencing. Our study confirms the previously reported <italic>GNAQ</italic> and <italic>GNA11</italic> mutation frequencies in UMs as well as the presence of monosomy 3 as a factor strongly indicating poor prognosis. Two cases with metastatic disease, but without monosomy of chromosome 3, showed loss of a small region in the distal part of chromosome 2p. Also, UMs leading to metastatic disease had more chromosomal aberrations than those without metastases. Three UMs lacking a <italic>GNAQ</italic> or <italic>a GNA11</italic> mutation showed a gain of chromosome 8q; one of these cases showed extensive chromothripsis. Another case (with suspect lung metastasis) showed focal chromothripsis. Our whole-genome copy-number analysis shows that focal loss of chromosome 2p may be involved in the metastatic spread of UMs without monosomy 3; metastatic UMs carry more chromosomal aberrations than those without metastases; and chromothripsis may play a role in the oncogenesis of UMs, but does not necessarily indicate a poor prognosis. The clinical and particularly diagnostic utility of these findings needs to be corroborated in a larger set of patients with UM.</p> </sec> </abstract>