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SF3B1 and EIF1AX mutations in uveal melanoma: a protective factor, or not?
Author(s) -
KILIC E,
KOOPMANS AE,
YAVUZYIGITOGLU S,
VAARWATER J,
VAN IJCKEN WFJ,
PARIDAENS D,
DE KLEIN JEMM
Publication year - 2014
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2014.4246.x
Subject(s) - sanger sequencing , exon , mutation , biology , bap1 , genetics , cancer research , medicine , melanoma , gene
Purpose The recent identification of mutations in the splicing factor SF3B1 and translation initiation factor EIF1AX prompted us to investigate the occurrence of these mutations in our uveal melanoma (UM) cohort. Methods Nineteen tumours were subjected to whole exome sequencing. In addition, the SF3B1 (exon 14) and EIF1AX (exon 1 and 2) mutation status was determined in 95 UM by Sanger sequencing. Results Mutations in SF3B1 were identified in 26% of UM and 19% harboured a mutation in either exon 1 or 2 of the EIF1AX gene. SF3B1 and EIF1AX mutations correlated significantly with good prognostic features such as spindle cell type, absence of closed vascular loops, positive BAP1 immunohistochemistry staining and disomy 3. Univariate analyses of EIF1AX mutated cases compared to those without EIF1AX mutations showed a significantly increase in disease‐free survival (DFS). Overall, the SF3B1 mutated cases did not show a significant difference in DFS compared to SF3B1 wild types. After stratifying for chromosome 3 status, patients with a disomy 3 UM and a SF3B1 mutation had a worse DFS compared to those with a disomy 3 UM and a wild type SF3B1 (P < 0.01). Conclusion SF3B1 and EIF1AX mutations occur in approximately a quarter of UM. Mutations in these genes associate with favourable prognostic features. In our study, we also reveal that patients with a normal chromosome 3 UM and a SF3B1 mutation have a higher risk of developing late metastasis.