Overview

This section shows a general overview of information for the selected study (COSU identifier) or publication (COSP identifier). Studies may have been performed by the Sanger Institute Cancer Genome Project, or imported from the ICGC/TCGA. You can see more information on the help pages.

Reference: SRSF2 Mutations in Uveal Melanoma: A Preference for In-Frame Deletions?
Paper ID: COSP47526
Authors: van Poppelen NM, Drabarek W, Smit KN, Vaarwater J, Brands T, Paridaens D, Kiliç E and de Klein A
Affiliation: Department of Ophthalmology, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands.
Journal: Cancers, 2019;11(8)
ISSN: 2072-6694
PMID: 31426461 (view at PubMed or Europe PMC)
Abstract: Background: Uveal melanoma (UM) is the most common primary ocular malignancy in adults in the Western world. UM with a mutation in SF3B1, 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 SF3B1 harbors similar chromosomal aberrations. Since, in addition to SF3B1, mutations in U2AF1 and SRSF2 have also been observed in hematological malignancies, UM without a SF3B1 mutation-but with the characteristic chromosomal pattern-might harbor mutations in one of these genes. Methods: 42 UMs were selected based on their chromosomal profile and wildtype SF3B1 status. Sanger sequencing covering the U2AF1 (exon 2 and 7) hotspots and SRSF2 (exon 1 and 2) was performed on DNA extracted from tumor tissue. Data of three UM with an SRSF2 mutation was extracted from the The Cancer Genome Atlas (TCGA). Results: Heterozygous in-frame SRSF2 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 SRSF2 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. Conclusions: Whereas in myelodysplastic syndrome predominantly missense SRSF2 mutations are described, the observed SRSF2 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: Curated
Genes Analysed: 39
Mutated Samples: 2
Total No. of Samples: 42

Mutation Matrix

This section shows the correlation plot between the top 20 genes and samples. There is more information in our help pages.

Genes	Mutated Samples

Non-Mutant Genes	Gene Id (COSG)

Variants

Coding Mutations
Non-Coding Mutations
CNV & Expr
Methylation
Fusions

This tab shows genes with mutations in the selected study/paper [more details]

Genes	Samples	CDS Mutation	AA Mutation

This tab shows non coding variant in the selected study/paper [more details]

Sample ID	Sample Name	ID NCV	Annotation	Zygosity	Chromosome	Genome start	Genome stop	Genome version	Strand	WT seq	Mut seq	FATHMM-MKL

This tab shows the gene expression and copy number variation data for this study [more details]

Table Information

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Sample	Gene	Expression	Expr Level (Z-Score) Over Expressed; Z-Score > 2.0 Under Expressed; Z-Score < -2.0 Normal; Z-Score within the range -2.0 to 2.0	CN Type	Minor Allele	Copy Number	CN Segment Posn.	Average Ploidy 1. N/A represents cases where the average ploidy value is not available( mostly ICGC samples). For some TCGA samples where the minor allele information is not available the average ploidy value could not be calculated. 2. For TCGA samples, the ASCAT algorithm was used to calculate the average ploidy. 3. For CGP samples, the PICNIC algorithm was used to calculate the average ploidy.	CNV

This table lists the samples in the selected study which have low/high methylation for each gene. [more details]

No data

This tab shows the fusion mutations observed in this sample [more details]

Gene	Sample Name	Id Sample(COSS)	CDS Mutation	Somatic status	Zygosity	Validated	Type

Samples

Mutant Samples
Non-Mutant Samples

This table shows mutated samples in the selected study/paper.

Sample Name	Mutation Count

This table shows samples without mutations in the selected study/paper.

Non-Mutant Samples	Sample Id (COSS)

GRCh38 · COSMIC v92