The NUP98 Gene as a Potential Modifier of NF2-Associated Tumors
Technical Report,01 Jun 2016,31 May 2017
Research Institute at Nationwide Childrens Hospital Columbus United States
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This exploratory hypothesis-driven award will test the hypothesis that the NUP98 gene, which plays an important role in nucleocytoplasmic transport, gene expression, mitotic checkpoint, and pathogenesis, is frequently mutated in VS and that NUP98 mutations are associated with disease severity. By next-generation sequencing, we previously identified missense mutations in the NUP98 gene in VS from two NF2 patients. We now confirmed that the changes include a D1156N mutation in exon 23, a Q1142E variant also in exon 23, and a K1178R mutation in exon 24, but not in the rest of NUP98 exons. By analyzing a total of 31 NF2-associated VS and 25 sporadic VS and by searching the COSMIC Catalogue of Somatic Mutations in Cancer database, we showed that NF2-associated VS have a higher incidence of harboring these mutationsvariant than sporadic VS or individuals without VS. These changes are heterozygous and are present in patients germline. Intriguingly, the amino acids affected by these NUP98 mutationsvariant are evolutionarily conserved among various species and are clustered in a coiled region of the protein. Our findings suggest that the NUP98 exons 23 and 24 encode an important functional domain and further implicate NUP98 as a potential genetic modifier for NF2.
- Medicine and Medical Research
- Genetic Engineering and Molecular Biology