Chordoma and chondrosarcoma gene profile implicat

Authors: Joseph H Schwab Patrick J Boland Narasimhan P Agaram Nicholas D Socci Tianhua Guo Gary C O’Toole Xinhui Wang Elena Ostroumov Christopher J Hunter Joel A Block Stephen Doty Soldano Ferrone John H Healey Cristina R Antonescu

Publish Date: 2008/07/19

Volume: 58, Issue: 3, Pages: 339-

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Abstract

Chordoma and chondrosarcoma are malignant bone tumors characterized by the abundant production of extracellular matrix The resistance of these tumors to conventional therapeutic modalities has prompted us to delineate the gene expression profile of these two tumor types with the expectation to identify potential molecular therapeutic targets Furthermore the transcriptional profile of chordomas and chrondrosarcomas was compared to a wide variety of sarcomas as well as to that of normal tissues of similar lineage to determine whether they express unique gene signatures among other tumors of mesenchymal origin and to identify changes associated with malignant transformation A HGU133A Affymetrix Chip platform was used to determine the gene expression signature in 6 chordoma and 14 chondrosarcoma lesions Validation of selected genes was performed by qPCR and immunohistochemistry IHC on an extended subset of tumors By unsupervised clustering chordoma and chondrosarcoma tumors grouped together in a genomic cluster distinct from that of other sarcoma types They shared overexpression of many extracellular matrix genes including aggrecan type II X collagen fibronectin matrillin 3 high molecular weightmelanoma associated antigen HMWMAA matrix metalloproteinase MMP9 and MMP19 In contrast T Brachyury and CD24 were selectively expressed in chordomas as were Keratin 8131518 and 19 Chondrosarcomas are distinguished by high expression of type IX and XI collagen Because of its potential usefulness as a target for immunotherapy the expression of HMWMAA was analyzed by IHC and was detected in 62 of chordomas and 48 of chondrosarcomas respectively Furthermore western blotting analysis showed that HMWMAA synthesized by chordoma cell lines has a structure similar to that of the antigen synthesized by melanoma cells In conclusion chordomas and chondrosarcomas share a similar gene expression profile of upregulated extracellular matrix genes HMWMAA represents a potential useful target to apply immunotherapy to these tumors

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