P. Francis, J. Fernebro, P. Edén, A. Laurell, A. Rydholm, H.A. Domanski, T. Breslin, C. Hegardt, Å. Borg and M. Nilbert
Intratumor versus Intertumor Heterogeneity in Gene Expression Profiles from Soft Tissue Sarcoma
to appear in Genes Chromosomes Cancer

Soft tissue sarcomas (STS) are heterogenous as regards genetic alterations, microscopic appearance, macroscopic features and clinical course. Concern has therefore been raised as to whether a single tumor sample can provide a gene expression profile representative of the entire tumor. We applied 27k cDNA microarray slides to assess the importance of intratumor versus intertumor heterogeneity of the gene expression profiles in two morphologically heterogenous STS. Multiple (8 and 10, respectively) tumor pieces were obtained from a malignant fibrous histiocytoma (MFH) and a leiomyosarcoma (LMS), and the expression patterns were compared with single tumor samples from 20 MFH and 16 LMS. Hierarchical clustering analysis of the expression profiles showed that samples from the same tumor clustered together and. The average intratumor distance was considerably lower than the average intertumor distance in both LMS and MFH. Also tumor subclusters that distinguished different macroscopic parts of the tumor could be discerned. We conclude that intratumor variability exists, but accurate gene expression profiling can be obtained using single samples also from large STS.

LU TP 05-17