title: Telomere stability genes are not mutated in osteosarcoma cell lines.
abstract: Osteosarcoma (OS), the most common primary bone tumor in adolescents and young adults, is characterized by a high degree of chromosomal abnormalities. Because telomeres are important for maintaining chromosomal integrity, it is plausible that germ-line or somatic mutations in the genes responsible for stabilizing the telomere complex could contribute to OS. We performed bi-directional sequence analysis in five OS cell lines and targeted all exons and proximal promoter regions in eight genes important in telomere stability: telomerase, the RNA component of telomerase (TERC), telomeric repeat binding factor 1, telomeric repeat binding factor 2, TERF1 interacting nuclear factor 2, human Rap1, protection of telomeres 1 and tankyrase. In this pilot study, we did not identify either somatic mutations or novel germ-line mutations in the five cell lines studied. However, we did confirm common genetic polymorphisms; an analysis of heterozygous sites suggests that loss of heterozygosity in OS is not present across these eight genes.
authors.affiliation: Section of Genomic Variation, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Advanced Technology Center, 8717 Grovemont Circle, Bethesda, MD 20892-4605, USA. savagesh@mail.nih.gov
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Savage
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Stewart
authors.forename: Jason S
authors.initials: JS
authors.lastname: Liao
authors.forename: Lee J
authors.initials: LJ
authors.lastname: Helman
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
mesh_terms: D001859:Bone Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D006801:Humans; D009154:Mutation; D012516:Osteosarcoma / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D019098:Telomerase / Q000235:genetics; D016615:Telomere; D035321:Telomeric Repeat Binding Protein 1 / Q000235:genetics; D035341:Telomeric Repeat Binding Protein 2 / Q000235:genetics
chemical_list: D035321:Telomeric Repeat Binding Protein 1; D035341:Telomeric Repeat Binding Protein 2; D019098:Telomerase