title: Absence of a telomere maintenance mechanism as a favorable prognostic factor in patients with osteosarcoma.
abstract: There are two telomere maintenance mechanisms (TMMs) in human tumors, telomerase activation (TA) and, more rarely, the process termed alternative lengthening of telomeres (ALT). Unlike most carcinomas, sarcomas, including osteosarcomas (OS), have been reported to display TA and ALT in more balanced proportions and, thus, present an opportunity to examine the impact of different TMMs on clinical tumor behavior. We studied OS samples from 62 patients for molecular evidence of TA and ALT. Kaplan-Meier analysis demonstrated that the absence of both TA and ALT (in 18%) was more strongly associated with improved survival (P = 0.05) than were stage (P = 0.16) or chemotherapy response (P = 0.18) in this group of patients with OS. Subsets of OS cases with either TA or ALT did not differ significantly from each other in clinical outcome. There were no significant associations of presence, absence, or type of TMM with patient age, stage, or chemotherapy response. Thus, the absence of a detectable TMM may identify a favorable clinical subset of OS patients. Our study also suggests that the likelihood of detecting correlations between TMMs and clinical outcome in studies of certain other tumor types might be improved if, in addition to TA, ALT is included in future analyses. Finally, we note that OS cases with a TA-/ALT+ phenotype seem to be as clinically aggressive as TA+ cases in terms of stage and clinical outcome.
authors.affiliation: Medical Service, Veterans Administration Palo Alto Health Care System, and Department of Medicine, Stanford University, Palo Alto, California 94304, USA. gary.ulaner@stanfordalumni.org
authors.forename: Gary A
authors.initials: GA
authors.lastname: Ulaner
authors.forename: Hsuan-Ying
authors.initials: HY
authors.lastname: Huang
authors.forename: Jesse
authors.initials: J
authors.lastname: Otero
authors.forename: Zhiquan
authors.initials: Z
authors.lastname: Zhao
authors.forename: Leah
authors.initials: L
authors.lastname: Ben-Porat
authors.forename: Jaya M
authors.initials: JM
authors.lastname: Satagopan
authors.forename: Richard
authors.initials: R
authors.lastname: Gorlick
authors.forename: Paul
authors.initials: P
authors.lastname: Meyers
authors.forename: John H
authors.initials: JH
authors.lastname: Healey
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Huvos
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Hoffman
authors.forename: Marc
authors.initials: M
authors.lastname: Ladanyi
mesh_terms: D000328:Adult; D000367:Age Factors; D001859:Bone Neoplasms / Q000201:enzymology / Q000235:genetics*; D004268:DNA-Binding Proteins; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D012516:Osteosarcoma / Q000201:enzymology / Q000235:genetics*; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D019098:Telomerase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D019098:Telomerase