Accession Number : AD1050097


Title :   The NUP98 Gene as a Potential Modifier of NF2-Associated Tumors


Descriptive Note : Technical Report,01 Jun 2016,31 May 2017


Corporate Author : Research Institute at Nationwide Childrens Hospital Columbus United States


Personal Author(s) : Chang, Long-Sheng


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1050097.pdf


Report Date : 01 Jun 2017


Pagination or Media Count : 45


Abstract : 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 mutations/variant 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 mutations/variant 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.


Descriptors :   neoplasms , genetic disorders , genes , mutations , gene expression , pathogenesis , amino acids


Subject Categories : Medicine and Medical Research
      Genetic Engineering and Molecular Biology


Distribution Statement : APPROVED FOR PUBLIC RELEASE