MedicalResearch.com Interview with:
Mark E. Hatley, M.D., Ph.D.
Molecular Oncology Division, Department of Oncology
St. Jude Children’s Research Hospital
Memphis, TN 38105
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma occurring in children. Tumors appear histologically and genetically as undifferentiated skeletal muscle and are thus thought to solely originate from early skeletal muscle cells. However, tumors occur throughout the body, including sites devoid of skeletal muscle. In addition, tumor location is a key feature of staging and 40% of patients develop RMS in the head and neck. Interestingly, head and neck muscle development is distinct from the development of trunk and limb muscle. Previously we described a model of rhabdomyosarcoma which occurred specifically in the head and neck and originated from non-muscle cells. In this study we investigated how normal development programs are hijacked to drive rhabdomyosarcoma location.
We demonstrated that RMS can originate from immature blood vessel cells that lie in between muscle fibers specifically in the head and neck. During development, these cells are hijacked, and become reprogrammed into rhabdomyosarcoma rather than mature endothelial cells. These RMS cells express factors important in head and neck muscle development. Our findings highlight that cell of origin contributes to RMS location and may explain why a high proportion of RMS occurs in the head and neck.
MedicalResearch.com: What should readers take away from your report?
Response: Here we demonstrate that rhabdomyosarcoma tumors that display the histological and molecular characteristics of undeveloped muscle cells can actually develop from immature endothelial cells that are hijacked during development. Typically, tumor origin is assumed on the histological and gene expression patterns of tumors. Our findings highlight why such assumptions are dangerous.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: Next, we need to determine the mechanism of transformation in our tumor model and apply these findings to patient samples to determine whether a similar mechanism of tumorigenesis occurs in human patients. If so, this could help us determine which patients are likely to respond better to therapy and identify new drug targets and therapies for patients.
Location specificity in fusion-negative rhabdomyosarcoma driven by cell of origin
AACR 2018 April 16, 2018
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