Detection of mutations in <i>SF3B1</i>, <i>EIF1AX</i> and <i>GNAQ</i> in primary orbital melanoma by candidate gene analysis

Rose, Anna M, Luo, Rong, Radia, Utsav K, Kalirai, Helen ORCID: 0000-0002-4440-2576, Thornton, Sophie ORCID: 0000-0001-7693-7279, Luthert, Philip J, Jayasena, Channa N, Verity, David H, Coupland, Sarah E ORCID: 0000-0002-1464-2069 and Rose, Geoffrey E
(2018) Detection of mutations in <i>SF3B1</i>, <i>EIF1AX</i> and <i>GNAQ</i> in primary orbital melanoma by candidate gene analysis. BMC CANCER, 18 (1). 1262-.

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<h4>Background</h4>Ocular melanoma is a rare but often deadly malignancy that arises in the uvea (commonest primary site), conjunctiva or the orbit. Primary orbital melanoma (POM) is exceedingly rare, with approximately 60 cases reported to date. Despite recent advances in our understanding of the genetics of primary uveal and conjunctival melanomas, this information is lacking for POM.<h4>Methods</h4>DNA was extracted from 12 POM tissues, with matched germline DNA (where available). MLPA was conducted to detect chromosomal alterations and Sanger sequencing used to identify point mutations in candidate melanoma driver genes (BRAF, NRAS, KRAS, GNA11, GNAQ), and other genes implicated in melanoma prognosis (EIF1AX, SF3B1). Immunohistochemistry was performed to analyse BAP1 nuclear expression.<h4>Results</h4>MLPA detected copy number alterations in chromosomes 1p, 3, 6 and 8. Sequencing of melanoma driver genes revealed GNAQ (p.Q209L) mutations in two samples; although it is possible that these samples represent extraocular spread of an occult uveal melanoma. A recurrent mutation in SF3B1 (p.R625H) was observed in indolent, but not aggressive, tumours; a mutation in EIF1AX (p.N4S) was detected in one patient with non-aggressive disease.<h4>Conclusions</h4>EIF1AX and SF3B1 mutations appear have a role in determining the clinical course of POM and detection of these changes could have clinical significance. Further in depth analysis of this rare group using differing 'omic technologies will provide novel insights into tumour pathogenesis.

Item Type: Article
Uncontrolled Keywords: Orbit, Melanoma, Primary, SF3B1, EIF1AX
Depositing User: Symplectic Admin
Date Deposited: 08 Jan 2019 16:51
Last Modified: 11 Oct 2023 20:12
DOI: 10.1186/s12885-018-5190-z
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