Muscle-specific Gene Expression in Rhabdomyosarcomas and Stages of Human Fetal Skeletal Muscle Development

Rhabdomyosarcomas (RMS) bear a morphological resemblance to developing striated muscle. It has been reported that two histologically distinct subtypes of RMS, embryonal and alveolar, behave differently in many clinical aspects, such as age distribution, primary site, and prognosis. We have investigated the expression of various genes, which are preferentially expressed in normal muscle tissue or cell culture (actins, myosins, and creatine kinases, and myogenic regulatory genes MyoD, myogenin, MRF4, and My/5), in embryonal and alveolar subtypes and compared the results to the stages of developing human fetal limb muscle. The data showed that each of the RMS tumors tested, regardless of histological features, expressed MyoD1 and MRF4 transcripts. Expression of the myogenin gene was detectable in all alveolar RMS (n = 8), whereas only 5 of 8 embryonal RMS expressed myogenin transcripts. Trace levels of Myf5 transcripts were visible in all alveolar RMS and 7 of 8 embryonal RMS. The α-skeletal, α-cardiac, and β- and -γ-cytoplasmic actin transcripts were detectable in all alveolar RMS. While the β-and γ-cytoplasmic actin transcripts were evident in all embryonal RMS, only 3 of 8 and 6 of 8 embryonal RMS expressed detectable levels of α- skeletal and α-cardiac actin transcripts, respectively. The embryonic form of myosin heavy chain was detectable in 1 of 8 of each type of tumor. Myosin light chain-1β transcripts were detectable in 4 of 8 alveolar RMS and 5 of 8 embryonal RMS. Brain creatine kinase transcripts were detectable in all alveolar RMS and 4 of 8 embryonal RMS, whereas none of the RMS samples contained detectable levels of the muscle form of creatine kinase. A comparison of the expression profiles with those of normal developing human fetal limb muscle (from 7.5 to 24 weeks' gestation) suggested that RMS resembled a relatively restricted segment of fetal muscle development. Furthermore, the data also showed a great deal of overlap in the differentiation state achieved by the embryonal and alveolar subtypes of RMS, suggesting that the clinicopathological differ ence between these two may not be due to malignant transformation of the cells from different positions in the normal pathway of myogenesis.