SRSF2 Mutations in Uveal Melanoma: A Preference for In-Frame Deletions?
Cancers (Basel) 2019, vol. 11, issue 8
Uveal melanoma (UM) is the most common primary ocular malignancy in adults in the Western world. UM with a mutation in
, 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
harbors similar chromosomal aberrations. Since, in addition to
, mutations in
have also been observed in hematological malignancies, UM without a
mutation-but with the characteristic chromosomal pattern-might harbor mutations in one of these genes.
42 UMs were selected based on their chromosomal profile and wildtype
status. Sanger sequencing covering the
(exon 2 and 7) hotspots and
(exon 1 and 2) was performed on DNA extracted from tumor tissue. Data of three UM with an
mutation was extracted from the The Cancer Genome Atlas (TCGA).
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
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.
Whereas in myelodysplastic syndrome predominantly missense
mutations are described, the observed
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.Link to full publication