Approximately 50% of ERMS is associated with RAS mutations, with NRAS mutations more common in adolescent cases and HRAS and KRAS mutations occurring in 70% of infant cases. Embryonal rhabdomyosarcoma is commonly driven by a mutation in the RAS family of proto-oncogenes, creating a powerful signal which is now known to promote tumor growth by preventing muscle lineage progression by blocking expression of the transcription factor myogenin. Inhibition of this signaling pathway with a cancer medication, trametinib, has been recently shown to overcome this differentiation block and reduce tumor progression in animal models of embryonal rhabdomyosarcoma.Tumor suppressor gene mutations, such as TP53 mutations, were shown in about 13% in the mutations and MYOD1 mutations were seen in about 3% of the mutations. Tumor suppressors signal the cell to stop the cell cycle and start apoptosis, known as programmed cell death, when the cell senses damage or irregular cell cycle growth patterns. Approximately 10% of ERMS cases include a loss of function mutation at TP53, which results in anaplasia, poor cellular differentiation that can be identified through nuclei that are larger and darker-colored than normal. An international study of more than 600 people with RMS showed worst outcomes in cases with anaplasia, regardless of fusion-status. Predisposing Conditions
Genetic conditions such as Gorlin syndrome, neurofibromatosis type 1, Beckwith-Wiedemann syndrome, Li-Fraumeni syndrome, Noonan syndrome, Costello syndrome, and DICER1 syndrome have been shown to predispose individuals to embryonal rhabdomyosarcoma. Risk factors associated with embryonal rhabdomyosarcoma include cigarette smoking, older age of birth parent, x-ray exposure, and maternal drug use.
However in "A Report From an International Consortium", the authors analyzed patient data from the Childrens Oncology Group (COG) and European paediatric Soft tissue sarcoma Study Group (EpSSG), hoping to identify and analyze any relationship between clinical outcomes and genetic mutations. The study comprised of 641 patients with sufficient data to analyze.Contrary to previous research, the findings of this study suggest that having RAS isoform mutations did not necessarily equate to a poor development of the disease. However, a pattern was found between the RAS isoform mutation seen and ones stage in life; HRAS isoform in infants, KRAS isoform in toddlers, and NRAS isoform in adolescence. This clinical study also found similar results as previous studies with the correlation of TP53 mutations and clinical outcome. TP53 mutations tended to result in a worsening development and clinical outcome of the disease. Although MYOD1 mutations make up a small percentage of ERMS, these mutations have been seen to have a negative prognosis and more studies should be conducted to understand how to treat the clinical condition of this specific mutation. Tumor Location
Tumor location plays an important role as RMS located in the parameningeal area, retroperitonium, pelvic, vulva, uterus, vagina, or trunk area genereally have poor prognosis. The anatomical position of parameningeal RMS makes it difficult to completely resect the entire tumor via surgery and may lead to tumor recurrence. Additionally, imaging that shows a tumor greater than 5 cm, presence of metastases, or positive lymph node status can indicate poor prognosis.