TY  - JOUR
AB  - 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.
AU  - Rumenapp, C.
AU  - Smida, J.
AU  - Gonzalez-Vasconcellos, I.
AU  - Baumhoer, D.
AU  - Malfoy, B.*
AU  - Hadj-Hamou, N.S.*
AU  - Sanli-Bonazzi, B.
AU  - Nathrath, M.
AU  - Atkinson, M.J.
AU  - Rosemann, M.
C1  - 11527
C2  - 30725
SP  - 433-437
TI  - Secondary radiation-induced bone tumours demonstrate a high degree of genomic instability predictive of a poor prognosis.
JO  - Curr. Genomics
VL  - 13
IS  - 6
PB  - Bentham Science
PY  - 2012
SN  - 1389-2029
ER  - 

TY  - JOUR
AB  - The use of particle ion beams in cancer radiotherapy has a long history. Today, beams of protons or heavy ions, predominantly carbon ions, can be accelerated to precisely calculated energies which can be accurately targeted to tumors. This particle therapy works by damaging the DNA of tissue cells, ultimately causing their death. Among the different types of DNA lesions, the formation of DNA double strand breaks is considered to be the most relevant of deleterious damages of ionizing radiation in cells. It is well-known that the extremely large localized energy deposition can lead to complex types of DNA double strand breaks. These effects can lead to cell death, mutations, genomic instability, or carcinogenesis. Complex double strand breaks can increase the probability of mis-rejoining by NHEJ. As a consequence differences in the repair kinetics following high and low LET irradiation qualities are attributed mainly to quantitative differences in their contributions of the fast and slow repair component. In general, there is a higher contribution of the slow component of DNA double strand repair after exposure to high LET radiation, which is thought to reflect the increased amount of complex DNA double strand breaks. These can be accurately measured by the γ-H2AX assay, because the number of phosphorylated H2AX foci correlates well with the number of double strand breaks induced by low or / and high LET radiation.
AU  - Schmid, T.E.*
AU  - Zlobinskaya, O.*
AU  - Multhoff, G.
C1  - 8318
C2  - 29980
SP  - 418-425
TI  - Differences in phosphorylated histone H2AX foci formation and removal of cells exposed to low and high linear energy transfer radiation.
JO  - Curr. Genomics
VL  - 13
IS  - 6
PB  - Bentham Science
PY  - 2012
SN  - 1389-2029
ER  - 

TY  - JOUR
AU  - Drobyshev, A.L.
AU  - Hrabě de Angelis, M.
AU  - Beckers, J.
C1  - 10254
C2  - 21313
SP  - 615-621
TI  - Artefacts and Reliability of DNA Microarray Expression Profiling Data. 
JO  - Curr. Genomics
VL  - 4
PY  - 2003
SN  - 1389-2029
ER  - 

TY  - JOUR
AU  - Beckers, J.
AU  - Hoheisel, J.*
AU  - Mewes, H.-W.
AU  - Vingron, M.*
AU  - Hrabě de Angelis, M.
C1  - 21925
C2  - 20260
SP  - 121-129
TI  - Molecular Phenotyping of Mouse Mutant Resources by RNA Expression Profiling.
JO  - Curr. Genomics
VL  - 3
PY  - 2002
SN  - 1389-2029
ER  -