GRCh38 · COSMIC v92

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
<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
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

This table shows genes with mutations in the selected study/paper [more details]
Genes Mutated Samples
This table shows genes without mutations in the selected study/paper [more details]
Non-Mutant Genes Gene Id (COSG)

Variants

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

Hide

The table currently shows only high value (numeric) copy number data. Copy number segments are excluded if the total copy number and minor allele values are unknown.

Click here to include all copy number data. For more detailed information about copy number data and gain/loss definitions click here.

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

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)