Genomic heterogeneity of osteosarcoma - shift from single candidates to functional modules.

摘要: Osteosarcoma (OS), a bone tumor, exhibit complex karyotype. On the genomic level highly variable degree of alterations in nearly all chromosomal regions and between individual tumors is observable. This hampers identification common drivers OS biology. To identify molecular mechanisms involved maintenance OS, we follow hypothesis that copy number-associated differences patients are intercepted on functional modules. The implementation based network approach utilizing number associated genes paired expression data protein interaction data. resulting modules tightly connected were interpreted regarding their biological functions potential prognostic significance. We identified an osteosarcoma assembling well-known lesser-known candidates. derived shows significant connectivity modularity suggesting affected by heterogeneous genetic share same context. participate several critical aspects cancer biology like DNA damage response, cell growth, motility which line with specifically deregulated but cancer. Further, could deduce possible significance for further investigation (e.g. EZR, CDKN2A, MAP3K5). Several those module located chromosome 6q. given systems provides evidence heterogeneity ordered system Different aberrations pointing to cellular vicinity form vital, already neoplastically altered, maintaining OS. observation, exemplarily now shown has been under discussion longer time, often hypothetical manner, can here be exemplified