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

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...

Full description

Saved in:
Bibliographic Details
Published in:BMC cancer 2018-12, Vol.18 (1), p.1262-1262, Article 1262
Main Authors: Rose, Anna M, Luo, Rong, Radia, Utsav K, Kalirai, Helen, Thornton, Sophie, Luthert, Philip J, Jayasena, Channa N, Verity, David H, Coupland, Sarah E, Rose, Geoffrey E
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Cancer
Cancer patients
Care and treatment
Chromosomes
Chromosomes, Human, Pair 1 - genetics
Chromosomes, Human, Pair 3 - genetics
Chromosomes, Human, Pair 6 - genetics
Chromosomes, Human, Pair 8 - genetics
Conjunctiva
Copy number
Deoxyribonucleic acid
DNA
DNA Copy Number Variations
EIF1AX
Eukaryotic Initiation Factor-1 - genetics
Eye diseases
Female
Gene expression
Gene mutation
Genetic aspects
Genetic testing
GTP-Binding Protein alpha Subunits, Gq-G11 - genetics
Health aspects
Humans
Immunohistochemistry
Immunotherapy
Leukemia
Male
Malignancy
Medical prognosis
Melanoma
Melanoma - genetics
Metastasis
Middle Aged
Multiplex Polymerase Chain Reaction
Mutation
Orbit
Orbital Neoplasms - genetics
Patients
Phosphoproteins - genetics
Primary
Prognosis
Radiation therapy
RNA Splicing Factors - genetics
Sequence Analysis, DNA
SF3B1
Tumors
Uvea
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
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. Despite recent advances in our understanding of the genetics of primary uveal and conjunctival melanomas, this information is lacking for POM. 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. 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. 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.
ISSN:1471-2407
1471-2407
DOI:10.1186/s12885-018-5190-z