Molecular classification of synovial sarcomas, leiomyosarcomas and malignant fibrous histiocytomas by gene expression profiling

Abstract

In this study, we have used genome-wide expression profiling to categorise synovial sarcomas, leiomyosarcomas and malignant fibrous histiocytomas (MFHs). Following hierarchical clustering analysis of the expression data, the best match between tumour clusters and conventional diagnosis was observed for synovial sarcomas. Eight of nine synovial sarcomas examined formed a cluster that was characterised by higher expression of a set of 48 genes. In contrast, sarcomas conventionally classified as leiomyosarcomas and MFHs did not match the clusters defined by hierarchical clustering analysis. One major cluster contained a mixture of both leiomyosarcomas and MFHs and was defined by the lower expression of a set of 202 genes. A cluster containing a subgroup of MFHs was also detected. These results may have implications for the classification of soft tissue sarcomas, and are consistent with the view that sarcomas conventionally defined as MFHs do not represent a separate diagnostic category.

Figures

Figure 1

(A) Two-dimensional cluster analysis of soft tissue sarcomas (horizontal) and 833 genes (vertical). Each column corresponds to a tumour, and each row corresponds to a gene. Red indicates overexpression relative to the median expression of all the samples, while green indicates underexpression. Grey indicates missing or excluded data. The dendrogram at the top (tumour clustering) shows the degree of similarity of expression pattern between the tumours, and the dendrogram on the side (gene clustering) shows the degree of similarity of expression pattern between the genes across the tumour samples. The shorter the branches, the more similar are the two joined tumours or genes (B) Magnified tumour dendrogram showing the type of tumour. Abbreviations: MFH, malignant fibrous histiocytoma; Leio, leiomyosarcoma; Synom, monophasic synovial sarcoma; Synob, biphasic synovial sarcoma.