Genetic Modeling of Human Rhabdomyosarcoma
- 1 June 2005
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 65 (11), 4490-4495
- https://doi.org/10.1158/0008-5472.can-04-3194
Abstract
Rhabdomyosarcoma, a malignancy showing features of skeletal muscle differentiation, is the most common soft tissue sarcoma of childhood. The identification of distinct clinical presentation patterns, histologic tumor types, and risk groups suggests that rhabdomyosarcoma is a collection of highly related sarcomas rather than a single entity. In an effort to understand this seemingly heterogeneous malignancy, we constructed a genetically defined but malleable model of rhabdomyosarcoma by converting less differentiated human skeletal muscle cell precursors (SkMC) and committed human skeletal muscle myoblasts (HSMM) into their malignant counterparts by targeting pathways altered in rhabdomyosarcoma. Whereas the two cell types were both tumorigenic, SkMCs gave rise to highly heterogeneous tumors occasionally displaying features of rhabdomyosarcoma, whereas HSMMs formed rhabdomyosarcoma-like tumors with an embryonal morphology, capable of invasion and metastasis. Thus, despite introducing the same panel of genetic changes, altering the skeletal muscle cell of origin led to different tumor morphologies, suggesting that cell of origin may dictate rhabdomyosarcoma tumor histology. The ability to now genetically induce human rhabdomyosarcoma-like tumors provides a representative model to dissect the molecular mechanisms underlying this cancer.Keywords
This publication has 26 references indexed in Scilit:
- Relationship Between MYCN Copy Number and Expression in Rhabdomyosarcomas and Correlation With Adverse Prognosis in the Alveolar SubtypeJournal of Clinical Oncology, 2005
- Altered expression and molecular abnormalities of cell-cycle-regulatory proteins in rhabdomyosarcomaLaboratory Investigation, 2004
- Soft tissue sarcomas of childhoodCancer Treatment Reviews, 2004
- Distinct requirements for Ras oncogenesis in human versus mouse cellsGenes & Development, 2002
- Human breast cancer cells generated by oncogenic transformation of primary mammary epithelial cellsGenes & Development, 2001
- Rhabdomyosarcoma – working out the pathwaysOncogene, 1999
- Mouse models in tumor suppressionOncogene, 1998
- SV40 Large T Antigen Interferes with Adult Myosin Heavy Chain Expression, but Not with Differentiation of Human Satellite CellsExperimental Cell Research, 1996
- Insulin-like Growth Factor Expression in Human Cancer Cell LinesPublished by Elsevier BV ,1996
- Cancer in the families of children with soft tissue sarcomaCancer, 1990