Recurrent RECQL4 imbalance and increased gene expression levels are associated with structural chromosomal instability in sporadic osteosarcoma

Neoplasia. 2009 Mar;11(3):260-8, 3p following 268. doi: 10.1593/neo.81384.


Osteosarcoma (OS) is an aggressive bone tumor with complex abnormal karyotypes and a highly unstable genome, exhibiting both numerical- and structural-chromosomal instability (N- and S-CIN). Chromosomal rearrangements and genomic imbalances affecting 8q24 are frequent in OS. RECQL4 gene maps to this cytoband and encodes a putative helicase involved in the fidelity of DNA replication and repair. This protective genomic function of the protein is relevant because often patients with Rothmund-Thomson syndrome have constitutional mutations of RECQL4 and carry a very high risk of developing OS. To determine the relative level of expression of RECQL4 in OS, 18 sporadic tumors were studied by reverse transcription-polymerase chain reaction. All tumors overexpressed RECQL4 in comparison to control osteoblasts, and fluorescence in situ hybridization analysis of tumor DNA showed that expression levels were strongly copy number-dependent. Relative N- and S-CIN levels were determined by classifying copy number transitions within array comparative genomic hybridization profiles and by enumerating the frequency of break-apart fluorescence in situ hybridization within 8q24 using region-specific and control probes. Although there was no evidence that disruption of 8q24 in OS led to an elevated expression of RECQL4, there was a marked association between increased overall levels of S-CIN, determined by copy number transition frequency and higher levels of RECQL4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Bone Neoplasms / genetics*
  • Child
  • Chromosomal Instability / genetics*
  • Female
  • Gene Dosage / genetics*
  • Gene Expression
  • Humans
  • In Situ Hybridization, Fluorescence
  • Male
  • Osteosarcoma / genetics*
  • RecQ Helicases / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction


  • RECQL4 protein, human
  • RecQ Helicases