Title:Secondary Radiation-Induced Bone Tumours Demonstrate a High Degree of Genomic Instability Predictive of a Poor Prognosis
Volume: 13
Issue: 6
Author(s): Christine Rumenapp, Jan Smida, Iria Gonzalez-Vasconcellos, Daniel Baumhoer, Bernard Malfoy, Nabila-Sandra Hadj-Hamou, Bahar Sanli-Bonazzi, Michaela Nathrath, Michael J. Atkinson and Michael Rosemann
Affiliation:
Keywords:
Genomic instability, Loss-of-heterozygosity, Osteosarcom, Predictive assay, Radiation-induced, SNP-array,
Therapy-related, Therapy response, heterozygosity, radiotherapy , induced bone sarcomas
Abstract: Secondary bone tumours arising in the field of a preceding radiotherapy are a serious late effect, in particular
considering the increasing survival times in patients treated for paediatric malignancies. In general, therapy associated tumours
are known to show a more aggressive behaviour and a limited response to chemotherapy compared with their primary
counterparts. It is not clear however whether this less favourable outcome is caused by inherent genetic factors of
the tumour cells or by a general systemic condition of the patient. To elucidate this we analysed a series of bone sarcomas
with a history of prior irradiation for the presence of genomic alterations and compared them with the alterations identified
earlier in primary osteosarcomas. We analysed seven radiation induced bone sarcomas for genome-wide losses of
heterozygosity (LOH) using Affymetrix 10K2 high-density single nucleotide polymorphism (SNP) arrays. Additionally,
copy number changes were analysed at two distinct loci on 10q that were recently found to be of major prognostic significance
in primary osteosarcomas. All the investigated tumours showed a LOH at 10q21.1 with 86% of cases (6/7) revealing
a total genome-wide LOH score above 2400 and more than 24% of the genome being affected. Our results indicate
similar genetic alterations in radiation induced sarcomas of bone and primary osteosarcomas with a poor prognosis. We
speculate that the high degree of genomic instability found in these tumours causes the poor prognosis irrespective of the
initiating event.
