title: Multiple mechanisms of telomere maintenance exist in liposarcomas.
abstract: OBJECTIVE
  Telomeres are specialized nucleoprotein complexes that protect and confer stability upon chromosome ends. Loss of telomere function as a consequence of proliferation-associated sequence attrition results in genome instability, which may facilitate carcinogenesis by generating growth-promoting mutations. However, unlimited cellular proliferation requires the maintenance of telomeric DNA; thus, the majority of tumor cells maintain their telomeres either through the activity of telomerase or via a mechanism known as alternative lengthening of telomeres (ALT). Recent data suggest that constitutive telomere maintenance may not be required in all tumor types. Here we assess the role and requirement of telomere maintenance in liposarcoma.
  
  
  METHODS
  Tumor samples were analyzed with respect to telomerase activity, telomere length, and the presence of ALT-specific subcellular structures, ALT-associated promyelocytic leukemia nuclear bodies. This multi-assay assessment improved the accuracy of categorization.
  
  
  RESULTS
  Our data reveal a significant incidence (24%) of ALT-positive liposarcomas, whereas telomerase is used at a similar frequency (27%). A large number of tumors (49%) do not show characteristics of telomerase or ALT. In addition, telomere length was always shorter in recurrent disease, regardless of the telomere maintenance mechanism.
  
  
  CONCLUSIONS
  These results suggest that approximately one half of liposarcomas either employ a novel constitutively active telomere maintenance mechanism or lack such a mechanism. Analysis of recurrent tumors suggests that liposarcomas can develop despite limiting or undetectable activity of a constitutively active telomere maintenance mechanism.
authors.affiliation: Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
authors.forename: Jay E
authors.initials: JE
authors.lastname: Johnson
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Varkonyi
authors.forename: Jaclyn
authors.initials: J
authors.lastname: Schwalm
authors.forename: Ryan
authors.initials: R
authors.lastname: Cragle
authors.forename: Andres
authors.initials: A
authors.lastname: Klein-Szanto
authors.forename: Arthur
authors.initials: A
authors.lastname: Patchefsky
authors.forename: Edna
authors.initials: E
authors.lastname: Cukierman
authors.forename: Margaret
authors.initials: M
authors.lastname: von Mehren
authors.forename: Dominique
authors.initials: D
authors.lastname: Broccoli
mesh_terms: D000328:Adult; D000368:Aged; D015139:Blotting, Southern; D049109:Cell Proliferation; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D016678:Genome; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008080:Liposarcoma / Q000378:metabolism / Q000648:ultrastructure*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009698:Nucleoproteins / Q000378:metabolism; D010534:Peritoneal Neoplasms / Q000378:metabolism / Q000648:ultrastructure; D012333:RNA, Messenger / Q000378:metabolism; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000648:ultrastructure*
chemical_list: D009698:Nucleoproteins; D012333:RNA, Messenger; D019098:Telomerase