The reason for rhabdomyosarcoma (RMS) is multifactorial, involving genetic mutations and subsequent disruptions in cell signaling pathways that regulate cell function. RMS may arise from tissues like skin, fat, or nerves.
Here's a more detailed breakdown:
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Genetic Mutations: The underlying cause involves alterations in the genetic material of cells. Specific mutations disrupt normal cell growth and differentiation, leading to the development of RMS. The exact mutations vary, contributing to different subtypes and prognoses.
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Disrupted Cell Signaling Pathways: These genetic mutations lead to dysregulation of signal transduction pathways. These pathways are crucial for controlling cell growth, differentiation, and survival. When these pathways are disrupted, cells may begin to grow uncontrollably and evade programmed cell death (apoptosis).
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Cellular Origin: While the specific cell of origin isn't always clear, RMS is thought to arise from primitive mesenchymal cells that are destined to become skeletal muscle. However, the reference suggests that RMS may also originate from tissues like skin, fat or nerves. These cells fail to properly differentiate and instead become cancerous.
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Subtypes: RMS is divided into several subtypes, each potentially having different genetic drivers and affecting treatment strategies. The two main subtypes are:
- Embryonal RMS (ERMS): More common in children, often associated with loss of heterozygosity (LOH) at chromosome 11p15.5 and mutations in genes regulating cell growth.
- Alveolar RMS (ARMS): More common in adolescents and young adults, frequently characterized by specific chromosomal translocations that fuse the PAX3 or PAX7 gene with the FOXO1 gene. These fusion genes create abnormal transcription factors that drive cancer development.
In summary, rhabdomyosarcoma arises due to a combination of genetic mutations that perturb cell signaling pathways, ultimately disrupting normal cell growth and differentiation of muscle cells (or potentially other tissue types).
