title: hCDC4 variation in osteosarcoma.
abstract: The hCDC4 gene (also known as Fbw7 or Archipelago) encodes an F-box protein that is responsible for targeting cyclin E for Skp1-cullin-F box protein (SCF) ubiquitination and proteosomal degradation. Disruption of this pathway has been associated with chromosomal instability and aneuploidy in several cancer cell lines and primary tumors. This study aimed to examine whether hCDC4 mutations contribute to aneuploidy in osteosarcoma. We analyzed 147 primary high-grade osteosarcoma specimens and 6 osteosarcoma cell lines. The protein truncation test (PTT) and single-strand conformation polymorphism (SSCP) analysis with subsequent sequencing were performed to detect alterations of the hCDC4 gene. All specimens exhibited the same PTT pattern of normal bands with less intense common bands. Two shifts were detected by SSCP, and subsequent DNA analysis identified one in-frame three-base GAG (424-426) deletion and one silent nucleotide substitution (C1261T). We conclude that somatic hCDC4 mutations are infrequent in osteosarcoma, and are unlikely to play an important role in aneuploidy of this tumor.
authors.affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, M5G 1X5.
authors.forename: Taiqiang
authors.initials: T
authors.lastname: Yan
authors.forename: Jay S
authors.initials: JS
authors.lastname: Wunder
authors.forename: Nalan
authors.initials: N
authors.lastname: Gokgoz
authors.forename: Kelly K Y
authors.initials: KK
authors.lastname: Seto
authors.forename: Robert S
authors.initials: RS
authors.lastname: Bell
authors.forename: Irene L
authors.initials: IL
authors.lastname: Andrulis
mesh_terms: D000782:Aneuploidy; D018797:Cell Cycle Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D044783:F-Box Proteins / Q000235:genetics*; D000073979:F-Box-WD Repeat-Containing Protein 7; D006801:Humans; D009154:Mutation; D012516:Osteosarcoma / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D017422:Sequence Analysis, DNA / Q000379:methods; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513273:FBXW7 protein, human; D044767:Ubiquitin-Protein Ligases