GRCh38 · COSMIC v92


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SRSF2 Mutations in Uveal Melanoma: A Preference for In-Frame Deletions?
Paper ID
van Poppelen NM, Drabarek W, Smit KN, Vaarwater J, Brands T, Paridaens D, Kiliç E and de Klein A
Department of Ophthalmology, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands.
Cancers, 2019;11(8)
ISSN: 2072-6694
PMID: 31426461 (view at PubMed or Europe PMC)
<i>Background:</i> Uveal melanoma (UM) is the most common primary ocular malignancy in adults in the Western world. UM with a mutation in <i>SF3B1</i>, a spliceosome gene, is characterized by three or more structural changes of chromosome 1, 6, 8, 9, or 11. Also UM without a mutation in <i>SF3B1</i> harbors similar chromosomal aberrations. Since, in addition to <i>SF3B1</i>, mutations in <i>U2AF1</i> and <i>SRSF2</i> have also been observed in hematological malignancies, UM without a <i>SF3B1</i> mutation-but with the characteristic chromosomal pattern-might harbor mutations in one of these genes. <i>Methods:</i> 42 UMs were selected based on their chromosomal profile and wildtype <i>SF3B1</i> status. Sanger sequencing covering the <i>U2AF1</i> (exon 2 and 7) hotspots and <i>SRSF2</i> (exon 1 and 2) was performed on DNA extracted from tumor tissue. Data of three UM with an <i>SRSF2</i> mutation was extracted from the The Cancer Genome Atlas (TCGA). <i>Results:</i> Heterozygous in-frame <i>SRSF2</i> deletions affecting amino acids 92-100 were detected in two UMs (5%) of 42 selected tumors and in three TGCA UM specimens. Both the UM with an <i>SRSF2</i> mutation from our cohort and the UM samples from the TCGA showed more than four structural chromosomal aberrations including (partial) gain of chromosome 6 and 8, although in two TCGA UMs monosomy 3 was observed. <i>Conclusions:</i> Whereas in myelodysplastic syndrome predominantly missense <i>SRSF2</i> mutations are described, the observed <i>SRSF2</i> mutations in UM are all in-frame deletions of 8-9 amino acids. This suggests that the R625 missense SF3B1 mutations and SRSF2 mutations in UM are different compared to the spliceosome gene mutations in hematological cancers, and probably target a different, as yet unknown, set of genes involved in uveal melanoma etiology.
Paper Status