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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Towards a new understanding and classification of chondrogenic neoplasias of the skeleton--biochemistry and cell biology of chondrosarcoma and its variants.

Despite substantial knowledge on the clinicopathology of chondrogenic skeletal neoplasms, only limited insights into the biology of the different tumor variants are available. There are virtually no established molecular markers for identification and classification of these neoplasms. In this paper, we present a systematic review of the biochemistry and cell biology of chondrogenic neoplasms of the bone focussing on our own recent investigations. The hallmark of all differentiated chondrogenic tumors is the presence of neoplastic chondrocytic cells responsible for the formation of the characteristic cartilaginous tumor matrix. These cells can show the full differentiation potential of physiologic chondrocytes depending on the tumor entity investigated. The high phenotypic diversity of physiologic chondrocytes explains the previously poorly understood, striking heterogeneity of the neoplastic cells and their surrounding extracellular matrix not only between different but also within chondrogenic tumors. In our studies, tumor classifications, so far based only on histomorphological criteria, were either confirmed or corrected: mesenchymal chondrosarcomas represent the prototypic neoplasm of pre-chondrogenic undifferentiated cells undergoing multifocal chondrocytic differentiation. Enchondromas, osteochondromas, and conventional chondrosarcomas are neoplasms of multi-phenotypically differentiated chondrocytes. Clear cell chondrosarcomas appear to be neoplasms of hypertrophic chondrocytic cells. A peculiar biology is displayed by dedifferentiated chondrosarcomas, which at least in most cases show neither "anaplasia" nor "dedifferentiation", but most likely "transdifferentiation" of part of the neoplastic cells to a cellular phenotype of a different mesenchymal differentiation lineage. Chondroblastomas do not show any chondroblastic differentiation at all. Our studies delineate molecular markers of chondrogenic neoplasms of the skeleton, which have the potential to be the basis of a new biology-orientated classification of skeletal neoplasms. The expression analysis of extracellular matrix genes, in particular of the collagen types, might be able to play herein a leading role in classification and diagnosis, similar to the cytokeratin subtypes or the CDs (cluster of differentiation) for the classification and diagnosis of neoplasms of the epithelia and the lymphatics.[1]


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