PAX7 expression in embryonal rhabdomyosarcoma suggests an origin in muscle satellite cells - PubMed (original) (raw)

PAX7 expression in embryonal rhabdomyosarcoma suggests an origin in muscle satellite cells

N Tiffin et al. Br J Cancer. 2003.

Abstract

Rhabdomyosarcoma (RMS) is a common paediatric soft tissue sarcoma that resembles developing foetal skeletal muscle. Tumours of the alveolar subtype frequently harbour one of two characteristic translocations that juxtapose PAX3 or PAX7, and the forkhead-related gene FKHR (FOXO1A). The embryonal subtype of RMS is not generally associated with these fusion genes. Here, we have quantified the relative levels of chimaeric and wild-type PAX transcripts in various subtypes of RMS (n=34) in order to assess the relevance of wild-type PAX3 and PAX7 gene expression in these tumours. We found that upregulation of wild-type PAX3 is independent of the presence of either fusion gene and is unlikely to contribute to tumorigenesis. Most strikingly, upregulated PAX7 expression is almost entirely restricted to cases without PAX3-FKHR or PAX7-FKHR fusion genes and may contribute to tumorigenesis in the absence of chimaeric PAX transcription factors. Furthermore, as myogenic satellite cells are known to express PAX7, this pattern of PAX7 expression suggests this cell type as the origin of these tumours. This is corroborated by the detection of MET (c-met) expression, a marker for the myogenic satellite cell lineage, in all RMS samples expressing wild-type PAX7.

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Figures

Figure 1

Figure 1

Average relative expression of PAX3, PAX3-FKHR, PAX7 and PAX7-FKHR in RMS samples. (A) Expression of PAX3 is shown relative to the expression of PAX3 in the cell line RDCL. (B) Expression of PAX3-FKHR is shown relative to the expression of PAX3-FKHR in the Rh30 cell line. (C) Expression of PAX7 is shown relative to the expression of PAX7 in the cell line RDCL (note different scale due to high levels of expression relative to RDCL=1.0). (D) Expression of PAX7-FKHR is shown relative to the expression of PAX7-FKHR in the RMS sample 6. Translocation status is shown. Error bars indicate standard deviation of four experiments.

Figure 2

Figure 2

RT–PCR to detect MET. Example of MET PCR product (240 bp) in lane 1, and restriction enzyme digest products (147, 93 bp) in lane 2.

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