The Impact of Tissue Heterogeneity on Gene Expression Analysis

Neuroblastomas can demonstrate marked intra and intertumoral heterogeneity primarily due to the spectrum of differentiation that occurs (see Chap. 8). This may result in tumor samples with a predominant primitive neuroblast component and others with a predominant differentiated ganglionic or Schwannian cell component. The interpretation of observed gene expression is therefore dependent on understanding the complexity of the cellular content. In heterogeneous samples, gene expression corresponding to very small but biologically significant components of tumors may not be evident using current methods and inter-sample comparisons can be limited by their lack of consistency in tissue content. Few reports have addressed these issues, but it is obvious that cell content is a major factor in NB as shown in the analyses below.

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