Abstract
Background: Spindle cell rhabdomyosarcoma (S-RMS) is a rare tumor that was previously considered as an uncommon variant of embryonal RMS (ERMS) and recently reclassified as a distinct RMS subtype with NCOA2, NCOA1, and VGLL2 fusion genes. In this study, we established a cell line (S-RMS1) derived from a four-month-old boy with infantile spindle cell RMS harboring SRF-NCOA2 gene fusion. Methods: Morphological and molecular characteristics of S-RMS1 were analyzed and compared with two RMS cell lines, RH30 and RD18. Whole genome sequencing of S-RMS1 and clinical exome sequencing of genomic DNA were performed. Results: S-RMS1 showed cells small in size, with a fibroblast-like morphology and positivity for MyoD-1, myogenin, desmin, and smooth muscle actin. The population doubling time was 3.7 days. Whole genome sequencing demonstrated that S-RMS1 retained the same genetic profile of the tumor at diagnosis. A Western blot analysis showed downregulation of AKT-p and YAP-p while RT-qPCR showed upregulation of endoglin and GATA6 as well as downregulation of TGFßR1 and Mef2C transcripts. Conclusion: This is the first report of the establishment of a cell line from an infantile spindle cell RMS with SRF-NCOA2 gene fusion. S-RMS1 should represent a useful tool for the molecular characterization of this rare and almost unknown tumor.
Highlights
Rhabdomyosarcoma (RMS) is the most common type of soft tissue sarcomas in children, accounting for 5%–8% of all pediatric tumors, and it may be congenital in 0.4%–2%of the cases [1]
The S-RMS1 cell line was established from the resected fresh tumor obtained through surgery, after neoadjuvant chemotherapy, from a four-month-old boy diagnosed at birth with an infantile S-RMS
Three different groups are included: (i) MyoD1 mutated spindle cell/sclerosing RMS that mostly occurs in older children and adults, with highly aggressive behavior; (ii) infantile S-RMS, with NCOA2, NCOA1, and VGLL2 fusions and favorable prognosis; and (iii) a subset of tumors probably representing a spindle cell variant of embryonal RMS (ERMS)
Summary
Rhabdomyosarcoma (RMS) is the most common type of soft tissue sarcomas in children, accounting for 5%–8% of all pediatric tumors, and it may be congenital in 0.4%–2%of the cases [1]. ERMS is more frequent and occurs in younger patients with a more favorable prognosis, whereas ARMS accounts for around 20% of all cases, and it is often diagnosed in older children with a highly aggressive clinical course. Since the 2013 WHO classification, these tumors are considered as a single rhabdomyosarcoma type [8], and they encompass spindle cell/sclerosing rhabdomyosarcomas with MyoD1 mutations, occurring in older children and young adults with a highly aggressive clinical behavior and infantile spindle cell rhabdomyosarcomas. This subgroup was originally described in 1994 under the name of rhabdomyofibrosarcoma [9]. S-RMS1 should represent a useful tool for the molecular characterization of this rare and almost unknown tumor
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