Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jan;72(1):e31428.
doi: 10.1002/pbc.31428. Epub 2024 Nov 7.

Clinicopathological Analysis of a European Cohort of MYOD1 Mutant Rhabdomyosarcomas in Children and Young Adults

Julia C Chisholm  1 , Joanna L Selfe  2 , Rita Alaggio  3 , Edmund Cheesman  4 , Angelica Zin  5 , Lucia Tombolan  6 , Antonina Parafioriti  7 , Giuseppe Maria Milano  8 , Madeleine Adams  9 , Sergey Popov  10 , Maja Česen  11 , Svetlana Tafjord  12 , Meriel Jenney  9 , Paula Z Proszek  13 , Helene Schlecht  14 , Daniela Di Carlo  15   16 , Janet Shipley  2 , Anna Kelsey  4
Affiliations

Clinicopathological Analysis of a European Cohort of MYOD1 Mutant Rhabdomyosarcomas in Children and Young Adults

Julia C Chisholm et al. Pediatr Blood Cancer. 2025 Jan.

Abstract

Background: Patients with PAX3/7-FOXO1 fusion-negative rhabdomyosarcomas (fnRMS) harbouring the rare L122R MYOD1 mutation have significantly poorer prognosis than other fnRMS. We undertook a detailed clinicopathological evaluation of a cohort of patients with MYOD1 mutated fnRMS in order to improve risk stratification and treatment options.

Procedure: Histological, mutational and clinical data from a cohort of patients with MYOD1 mutant RMS treated in Europe were analysed.

Results: Thirty-two cases with mutant MYOD1 RMS were identified from patients enrolled in sequential European rhabdomyosarcoma clinical trials from 1992 to 2022 (n = 22) and non-trial cohorts (n = 10). Thirty cases had the recurrent L122R missense mutation, one case harboured a K124E mutation and one case had a truncating mutation (S63X). Increased MyoD1 and reduced MYF4 immunostaining were consistent features of MYOD1L122R-mutated RMS. Applying the risk stratification of the European paediatric Soft tissue sarcoma Study Group (EpSSG) RMS2005 trial, among 20 localised RMS cases that could be assigned a risk category, one was Very High Risk, 13 were High Risk and six were Standard Risk. Eight patients had distant metastases at diagnosis. Of the 25 patients with adequate clinical follow-up data, 15/25 (60%) patients had an event at a median time of 9 months (12/15 included failure of local control) and 13/25 (52%) died of disease.

Conclusion: This MYOD1 mutant cohort demonstrates increased MYOD and reduced MYF4 immunostaining, high risk of local failure and poor survival in agreement with other studies. Increased treatment intensity and improved local control should be considered for these patients.

Keywords: MYOD1; histology; mutation analysis; outcome; rhabdomyosarcoma.

PubMed Disclaimer

References

    1. D. Williamson, E. Missiaglia, A. de Reyniès, et al., “Fusion Gene‐Negative Alveolar Rhabdomyosarcoma is Clinically and Molecularly Indistinguishable From Embryonal Rhabdomyosarcoma,” Journal of Clinical Oncology 28 (2010): 2151–2158.
    1. S. Kohsaka, N. Shukla, N. Ameur, et al., “A Recurrent Neomorphic Mutation in MYOD1 Defines a Clinically Aggressive Subset of Embryonal Rhabdomyosarcoma Associated With PI3K‐AKT Pathway Mutations,” Nature Genetics 46 (2014): 595–600.
    1. J. F. Shern, J. Selfe, E. Izquierdo, et al., “Genomic Classification and Clinical Outcome in Rhabdomyosarcoma: A Report from an International Consortium,” Journal of Clinical Oncology 39 (2021): 2859–2871.
    1. R. Alaggio, L. Zhang, Y. Sung, et al., “A Molecular Study of Pediatric Spindle and Sclerosing Rhabdomyosarcoma: Identification of Novel and Recurrent VGLL2‐Related Fusions in Infantile Cases,” American Journal of Surgical Pathology 40 (2016): 224–235.
    1. K. Szuhai, D. de Jong, W. Y. Leung, C. D. M. Fletcher, and P. C. W Hogendoorn, “Transactivating Mutation of the MYOD1 Gene is a Frequent Event in Adult Spindle Cell Rhabdomyosarcoma,” Journal of Pathology 232 (2014): 300–307.

Substances

LinkOut - more resources