Firstly, according to the research that was conducted by Kashi et al (2016) it indicate that ERMS is a genetically heterogeneous that arise as sporadic tumours. As much as this particular condition occurs occasionally but it is highly associated with a number of familial syndrome that are caused by a germ-line mutation in oncogenesis- related signal transduction pathway. In other words there are several pathways that are capable of driving the development of ERMS.So although ERMS has no consistent chromosal rearrangement, a molecular analyses of polymorphic loci reveals a frequent allelic loss on chromosome 11. Allellic loss is manifested by the absence of one of two alleles in patient tumour cells which indicate a genetic mutation event such as chromosome loss, election or mitotic recombination that eliminate allele and surrounding chromosome region (Xia et al :2002).
Usually the ERMS allelic loss occurring in the smallest region of chromosome 11p15.5 and the presence of a consistent region of allelic loss indicate the inactivation of tumour suppressor gene in the associated malignancy (Xia et al:2002).
On the other hand, great scientists Xinsun et al (2015), reveals that RMS can occur either as primary malignancy or as a malignant terotomatous tumour. So a malignant transformation occurs cytogenetically due to the accumulation of somatic mutations by the acquisition of tumour specific chromosal translocations. RMS is characterized by the gains or loose of a specific chromosome, so the focal region where by gain and amplification occurs cover 12q13.3-q14.1, 8p11.2-11.2, CDK4, myCN, GLI, MDMZ, FGFRI and FGFR4. As it was already mention early that RMS is classified into three forms which is embryonal, alveolar and pleomorphic ,so ERMS is mainly indicated by the gains or loose of specific whole chromosome whereas ARMS is characterised by the region of genomic amplifications ( Xinsun et al:2015).
ERMS exhibits a loss of imprinting ,leading to a twofold gene dosage effect .ERMS tumorigenesis can results from inactivation of the parental bias of chromosome 11p15which is the most common rearrangement in ERMS(Xinsun et al:2015).
Furthermore RMS originates as a consequence of regulatory disruption of growth and differentiation of myogenic precursor cells. Progenitor cells reside in muscle and their activation results in either proper myogenesis or aberrant signalling pathways leading to the development of RMS (Kashi et al: 2016). Based on the sketal muscle lineage RMS reflects the undifferentiated myogenic nature and the genus that upregulated includes FGFR4,NOTCH2,Ube2c,UHRFI and YWHAB genes contribute to the failure of RMS cells to complete normal skeletal muscle development and progress to an alternative fate. Amplification of MDM2 in a RMS cell lines interferes with MYOD activity and inhibit overt muscle cell differentiation (Xinsun et al: 2015).
In addition, most RMS tumour hijacked a common receptor tyrosine kinase/RAS/PiK 3 CA genetic axis. This could occur via two alternative mechanism rearrangement of a PAX gene and accumulation of mutation that were downstream targets of the PAX fision protein. Skeletal muscle cell has a no bust antioxidant defense system to protect the DNA, Lipids and Protein from the delections effects of excess reactive oxygen species (Xinsun et al:2015).