Molecular markers


Last author update: 14 December 2022
Last staff update: 14 December 2022

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PubMed Search: MyoD1

Zhonghua Liu, M.D., Ph.D.
Patricia Tsang, M.D., M.B.A.
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Cite this page: Liu Z, Tsang P. MyoD1. website. Accessed May 20th, 2024.
Definition / general
  • Located on 11p15.1, MYOD1 (myogenic differentiation 1) encodes myogenic transcriptional regulatory protein expressed in early skeletal muscle differentiation during skeletal muscle development and regeneration
  • MyoD1 is a sensitive immunostain for rhabdomyosarcoma (RMS) but lacks specificity
  • Somatic recurrent mutation is associated with poor prognosis in spindle cell / sclerosing rhabdomyosarcomas (SRMS)
Essential features
  • MYOD1 encodes a nuclear protein that promotes transcription of muscle specific target genes and regulates muscle cell differentiation
  • MYOD1 p.L122R is a recurrent hotspot mutation in SRMS with unfavorable prognosis
  • Mutant cases typically show intense immunohistochemical (IHC) staining (Eur J Cancer 2022;172:367)
  • Diffuse, strong nuclear staining in SRMS and variable expression in alveolar, embryonal and pleomorphic RMS
  • MYOD1 gene: myogenic differentiation 1 gene
  • Myoblast determination protein 1
  • MYOD1 c.365T>G, p.L122R substitution missense mutation (COSMIC: Mutation COSV51452486 [Accessed 15 November 2022])
  • MyoD1 immunostain
  • Class C basic helix - loop - helix protein 1 (BHLHC1)
  • Myogenic factor 3 (MYF3)
Clinical features
  • L122R mutated SRMS cases predominantly occur in the head and neck or paramengineal region (88%) (J Clin Oncol 2021;39:2859)
    • Age range of 2 - 94 years, commonly in adolescents and young adults
    • Generally absent in congenital / infantile cases which tend to harbor gene fusions without involving MYOD1 (Mod Pathol 2019;32:27)
    • Mutation is associated with aggressive clinical course and typically a fatal outcome in both pediatric and adult patients
Uses by pathologists
Prognostic factors
Microscopic (histologic) images

Contributed by Zhonghua Liu, M.D., Ph.D.
Spindle cell / sclerosing rhabdomyosarcoma Spindle cell / sclerosing rhabdomyosarcoma

Spindle cell / sclerosing RMS

MyoD1 immunohistochemistry


Positive staining - normal
  • Normal fetal skeletal muscle (myoblasts of developing skeletal muscle)
    • Downregulated during later stages of differentiation
    • Nuclear staining pattern
  • Areas of skeletal muscle regeneration in myopathies and neurogenic muscle atrophy disorders (Acta Neuropathol 1994;87:605)
Positive staining - disease
Negative staining
  • Normal adult muscle
Molecular / cytogenetics description
Molecular / cytogenetics images

Images hosted on other servers:

MYOD1 CTG>CGG p.L122R mutation (SRMS)

MYOD1 T>G p.L122R mutation (SRMS)

Sample pathology report
  • Soft tissue mass, left thigh, needle core biopsy:
    • Malignant spindle cell neoplasm, consistent with spindle cell rhabdomyosarcoma (see comment and addendum)
    • Comment: The needle core biopsy demonstrates fascicles of spindle cell proliferation with a herringbone growth pattern. Rare rhabdomyoblasts are present. Mitoses are brisk. The neoplastic cells stain positively for MyoD1, desmin and myogenin (focal) and negatively for AE1 / AE3, S100, CD34 and SMA. The morphology and immunophenotypic profile are consistent with spindle cell rhabdomyosarcoma.
    • Addendum: MYOD1 p.L122R mutation was detected. Notably, this somatic mutation is associated with an aggressive clinical course in spindle cell / sclerosing rhabdomyosarcoma. Per xxx (reference laboratory) report, PCR was performed on genomic DNA extracted from formalin fixed paraffin embedded tumor tissue. Sanger sequencing of the purified amplicon confirmed a missense substitution of MYOD1 (p.L122R, T>G), consistent with a hotspot mutation reported in a subset of spindle cell / sclerosing rhabdomyosarcoma.
Board review style question #1

A 20 year old man with a 4 cm lump in the scalp underwent a core needle biopsy. H&E and MyoD1 immunostain images are shown above. Which genetic abnormality is most likely seen in this tumor?

  1. BRAF p.V600E mutation
  2. EWSR1::TFCP2 fusion
  3. MYOD1 p.L122R mutation
  4. SS18::SSX1 fusion
  5. VGLL2::NCOA2 fusion
Board review style answer #1
C. MYOD1 p.L122R is the most likely recurrent genetic abnormality in this MyoD1 expressing spindle cell / sclerosing rhabdomyosarcoma. This tumor commonly involves the head and neck region in adolescents and young adults. Congenital / infantile cases are more likely to harbor fusions involving the VGLL2, SRF, TEAD1, NCOA2 and CITED2 genes.

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Reference: MyoD1
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