Mxi1 mutations in human neurofibrosarcomas

Mxil is thought to negatively regulate Myc function and may therefore be a potential tumor suppressor gene. Little effort has Set been made to find al terations involving this gene in human solid tumors. We screened 31 human g astric cancers, 7 esophageal cancers, 85 bone and soft tissue tumors of var ious types, including 4 neurofibrosarcomas, We also examined 29 human tumor cell lines consisting of 12 esophageal cancers, 7 glioma/glioblastomas and 10 others for Mxil mutations in exons 1, 2, 4 (HLH domain), 5 and 6, Polym erase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and subsequent sequencing revealed three distinct polymorphisms in the intron- exon boundary upstream from exon 6, We discovered a missense mutation, GCA to GTA (Ala 54 Val), in exon 2 in a neurofibrosarcoma patient (case 1), two missense mutations, AAA to CAA (Lys 118 Gin) and GAA to GCA (Glu 154 Gly) in exon 5 of another neurofibrosarcoma patient (case 2), and 3 amino acid s ubstitutions, GTG to GCG (Val 179 Ala), GTT to GCT (Val 181 Ala) and TTC to CTC (Phe 186 Leu), in a third neurofibrosarcoma patient (case 3), Ln case 3, loss of heterozygosity was also demonstrated by informative (TTC),I(TTC) 2 polymorphism. Our data demonstrate that mutations occur in the Mxil gene in neurofibrosarcoma, Missense mutations in the functional domain of Mxil i n these cases may be involved in the pathogenesis of neurofibrosarcoma.