Osteosarcoma microaberrations

Background: Osteosarcoma (OS) is a very aggressive bone tumor characterized by highly abnormal complex karyotypes. With the improved resolution offered by array comparative genomic hybridization (array CGH) platforms, it is possible to readily detect cryptic microaberrations in genomic DNA. The identification of these microaberrations in genetic syndromes is currently the focus of many array CGH studies, but there have been no analyses to date documenting the occurrence of microaberrations in tumors. Results: In this study we utilized high-resolution oligonucleotide array CGH to identify novel microaberrations under ~750 kb in four OS-derived cell lines: U-2 OS, HOS, MG-63 and SAOS-2. Comparative analysis of these alterations showed that SAOS-2 harbored the most microaberrations at 17, followed by MG-63 with 11, HOS with 9 and U-2 OS with 6. SAOS-2, which has a TP53 mutation, exhibited the highest level of chromosomal instability in previous studies by our group; whereas U-2 OS, which has wild-type p53 status, exhibited the least instability. A consensus region of gain at 5p15.33 was detected in three of the four OS-derived cell lines (HOS, MG-63 and SAOS-2) by aCGH. Of these consensus gains, one was a microaberration of 500 kb in SAOS-2, and confirmed by fluorescence in situ hybridization analysis. It should be noted that this microaberration is immediately telomeric to the TERT gene, which also showed gain. TERT is correlated with increased tumor aggression, as well as decreased progression free survival in OS patients. Keywords: comparative genomic hybridization (array CGH) This genome-wide analysis is the first study to utilize oligonucleotide array CGH to identify microaberrations in OS, likely to contain genes involved in OS tumor oncogenesis. A better understanding of the underlying molecular genetic events leading to tumor initiation and progression could result in the identification of prognostic markers and therapeutic targets.