MYOD1 as a prognostic indicator in rhabdomyosarcoma

Abstract

Background/objectives: Rhabdomyosarcoma (RMS) is characterized by the expression of the myogenic regulatory protein MYOD1. Histologic types include alveolar, embryonal (ERMS), and spindle cell sclerosing RMS (SRMS). SRMS harbors MYOD1 mutations in a subset of adult cases in association with poor prognosis.Design/methods: To study the level of MYOD1 protein expression and its clinical significance, we have analyzed variable numbers of pediatric (<18 years of age) and adult (age range ≥18 to 35 years) ERMS and SRMS cases for presence or absence of MYOD1 immunoreactivity in correlation with clinical outcome and MYOD1 L122R mutations.Results: Lack of MYOD1 immunoreactivity, identified in 23.8% of nonalveolar RMS (non-ARMS) cases, was more prevalent in SRMS (44%) than ERMS (17.2%) and was significantly associated with low overall survival and unfavorable tumor sites (p < .05).Lack of MYOD1 immunoreactivity was not associated with MYOD1 L122R mutations, which were identified in 3/37 (8%) cases including only two of 31 (6.5%) pediatric cases, one of 11 or 9% pediatric SRMS, and one case of infant ERMS. Conclusion:These studies highlight the prognostic role of MYOD1 in non-ARMS. Lack of MYOD1 immunoreactivity is associated with poor prognosis in ERMS and SRMS.MYOD1 gene mutations are generally infrequent in pediatric RMS. Although mutations are predominant in SRMS, they may exceptionally occur in infantile ERMS.

Molecular testing of rhabdomyosarcoma in clinical trials to improve risk stratification and outcome: A consensus view from European paediatric Soft tissue sarcoma Study Group, Children's Oncology Group and Cooperative Weichteilsarkom-Studiengruppe

“…Recently, a lack of nuclear MYOD1 immunostaining in ERMS and spindle cell sclerosing RMS, that contrasts to the high level of staining associated with L122R mutations, has also been associated with inferior outcome, although numbers reported are so far small [92]. As MYOD1 is a key determinant of apparent differentiation status in RMS tumours, this lack of nuclear expression may reflect a relatively undifferentiated state.…”

Identify potential driver genes for PAX-FOXO1 fusion-negative rhabdomyosarcoma through frequent gene co-expression network mining

“…All these evidences support that TWIST1 is another potential driver gene in RMS. MYOD1 is a myogenic regulatory factor and is necessary for muscle fiber differentiation ( 61 ). However, its role in FN-RMS samples that we examined shows inconsistent results.…”

“…While in the St. Jude dataset, MYOD1 CN amplification is observed in FN-RMS, but no significant changes in term of gene expression between two fusion status subtypes. Zibat et al identified that MYOD1 is significantly lower expressed in FN-RMS (ERMS and FN-ARMS) than FN-RMS (PAX-FOXO1 ARMS) (62), and lacking of MYOD1 is associated with poor prognosis in ERMS (61). In addition, TWIST1 is a known MYOD1 inhibitor (63) and Tremblay et al have observed that YAP1 and TWIST1 could inhibit MYOD1 activity in ERMS (58).…”

NanoString Digital Molecular Profiling of Protein and microRNA in Rhabdomyosarcoma

“…Diagnoses were confirmed by re-review of the histologic slides for the characteristic morphology and immunophenotype (Table 1). Patients and tumors were selected from our previous study [15] and were classified into three prognostic and histologic groups, based on clinical follow-up information and calculation of overall survival (Figure 1A). Group 1 was defined as tumors with adverse or poor prognosis and contained both ERMS and SRMS.…”

“…Read-out of protein expression was estimated using signal to noise ratio (SNR) and quantified as 1-3 (SNR = 1 indicates protein signal similar to background noise; SNR = 3 indicates signal is three times the background noise). and tumors were selected from our previous study [15] and were classified into th prognostic and histologic groups, based on clinical follow-up information and calculat of overall survival (Figure 1A). Group 1 was defined as tumors with adverse or poor pr nosis and contained both ERMS and SRMS.…”