Abstract
BackgroundOcular 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.MethodsDNA 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.ResultsMLPA 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.ConclusionsEIF1AX 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.
Highlights
Ocular melanoma is a rare but often deadly malignancy that arises in the uvea, conjunctiva or the orbit
We examined Primary orbital melanoma (POM) for alterations in candidate melanoma driver genes (BRAF, NRAS, KRAS, GNA11, GNAQ) and genes implicated in uveal melanoma (UM) prognosis (EIF1AX, SF3B1, BAP1)
In this study we examined the largest reported clinical series of POM for mutations implicated in melanoma, giving the first report of genetic alterations in this rare tumour
Summary
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. Ocular melanoma is a rare, generally lethal, malignancy that can arise in the uveal tract, the conjunctiva, or the ocular adnexa (eyelid or orbit). Orbital melanoma occurs either as primary disease, as secondary disease (local invasion from an ocular or sinonasal primary tumour), or as a metastasis from the contralateral eye or from the skin. Primary orbital melanoma (POM) is extremely rare, with approximately 60 cases reported to date. The disease is considered to have a very poor prognosis, but there appears to be a subset of patients who have long-survival [6, 7]
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