title: Mxi1 mutations in human neurofibrosarcomas.
abstract: Mxi1 is thought to negatively regulate Myc function and may therefore be a potential tumor suppressor gene. Little effort has yet been made to find alterations involving this gene in human solid tumors. We screened 31 human gastric cancers, 7 esophageal cancers, 85 bone and soft tissue tumors of various types, including 4 neurofibrosarcomas. We also examined 29 human tumor cell lines consisting of 12 esophageal cancers, 7 glioma/glioblastomas and 10 others for Mxi1 mutations in exons 1, 2, 4 (HLH domain), 5 and 6. Polymerase 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 Gln) and GAA to GGA (Glu 154 Gly) in exon 5 of another neurofibrosarcoma patient (case 2), and 3 amino acid substitutions, 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). In case 3, loss of heterozygosity was also demonstrated by informative (TTC)3/(TTC)2 polymorphism. Our data demonstrate that mutations occur in the Mxi1 gene in neurofibrosarcoma. Missense mutations in the functional domain of Mxi1 in these cases may be involved in the pathogenesis of neurofibrosarcoma.
authors.affiliation: First Department of Pathology, Hamamatsu University School of Medicine.
authors.forename: X J
authors.initials: XJ
authors.lastname: Li
authors.forename: D Y
authors.initials: DY
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Zhu
authors.forename: R J
authors.initials: RJ
authors.lastname: Guo
authors.forename: X D
authors.initials: XD
authors.lastname: Wang
authors.forename: K
authors.initials: K
authors.lastname: Lubomir
authors.forename: K
authors.initials: K
authors.lastname: Mukai
authors.forename: H
authors.initials: H
authors.lastname: Sasaki
authors.forename: H
authors.initials: H
authors.lastname: Yoshida
authors.forename: T
authors.initials: T
authors.lastname: Oka
authors.forename: R
authors.initials: R
authors.lastname: Machinami
authors.forename: K
authors.initials: K
authors.lastname: Shinmura
authors.forename: M
authors.initials: M
authors.lastname: Tanaka
authors.forename: H
authors.initials: H
authors.lastname: Sugimura
mesh_terms: D000328:Adult; D000368:Aged; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018319:Neurofibrosarcoma / Q000235:genetics*; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D014157:Transcription Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C079440:MXI1 protein, human