Stuck in a balancing act: histone methyltransferase activity of KMT1A traps alveolar rhabdomyosarcomas in an undifferentiated state.

摘要

Rhabdomyosarcoma (RMS) is a pedi-atric tumor of skeletal muscle that bears a strong resemblance to myoblasts, the undifferentiated but committed cells of skeletal muscle. The two most common subtypes of RMS, alveolar (ARMS) and embryonal (ERMS), exhibit different morphologies as well as generally affecting different patient populations, but both share the common characteristic of a failure to properly execute the myogenic transcriptional differentiation program. While the most common genetic lesion in ERMS is a loss of 11p15, ARMS are notable for frequently exhibiting a gene fusion between either PAX3 or PAX7 and the forkhead transcription factor FOXO1A, a fusion that results in abnormally strong expression of PAX targets.