This is clearly a major advance in the understanding of osteosarcoma (OS) tumorigenesis. It is the most comprehensive and sophisticated genomic study published on this disease.  

The study explains a new mechanism of how OS is generated with a biallelic deletion centered on the short arm of chromosome 17, in the region where p53 sits. This tumor suppressor gene was known to be key in OS, but the mechanism by which this relevance was reflected in the associated genetic instability and high complexity of structural aberrations in the OS genome was not known. The loss-translocation-amplification (LTA) chromothripsis [breakage and rearrangement of chromosome fragments] mechanism they describe appears quasi-exclusive to OS, something that was already known, as the OS genome is almost unique among all cancers.  

Loss of heterozygosity (LOH) is described as the starting point of the chromothripsis LTA mechanism and genome-wide LOH levels appear to predict increased aggressiveness of OS. These data deserve further clinical correlation, as the prognosis of OS remains very poor.  

This study, thanks to the sophisticated genomic analysis of multiple regions of OS tumors and the associated extremely complex bioinformatics analysis, has made it possible to decipher a puzzle that seemed unfathomable. The mechanisms behind such an aberrant genome as that of OS seem to respond to a mechanism that has its biological logic and that allows us to understand how the chromosomal instability of the OS genome propagates. It would be likened to a bomb that, when it explodes, generates new subsequent explosions to continue generating new explosions in a chain.