Two cases of primary supratentorial intracranial rhabdomyosarcoma with DICER1 mutation which may belong to a "spindle cell sarcoma with rhabdomyosarcoma-like feature, DICER1 mutant".
Additional in trans DICER1 missense somatic mutations in the IIIb DICER1 domain were found both in the cystic nephroma and in the rhabdomyosarcoma, suggesting that neoplasms in this family might arise from the unusual two-hit mechanism for DICER-derived tumorigenesis in which after the presence of a truncated constitutive protein, a neomorphic DICER1 activity is somatically adquired.
We identified Bub1b as an essential element for the growth and survival of rhabdomyosarcoma (RMS) cells using a bar-coded, tetracycline-inducible short hairpin RNA (shRNA) library screen.
These data suggest that the genetic progression in rhabdomyosarcoma from MVA and non-MVA cases may be similar, but that somatic BUB1B mutations are unlikely to be common in sporadic childhood cancers known to be associated with MVA.
In family 2, immunohistochemistry analysis showed isolated loss of PMS2 expression in all tumours in the affected patients, including rhabdomyosarcoma itself and the surrounding normal tissue.
In family 2, immunohistochemistry analysis showed isolated loss of PMS2 expression in all tumours in the affected patients, including rhabdomyosarcoma itself and the surrounding normal tissue.
Rhabdomyosarcomas are malignancies associated with a rhabdomyoblastic phenotype which can be demonstrated morphologically or by immunohistochemistry for MYOD1 and myogenin.
We investigated 30 cases of MYOD1-mutant rhabdomyosarcoma (12 previously reported and 18 newly diagnosed) with an age range of 2-94 years, including 15 children.
The expanding morphological and genetic spectrum of MYOD1-mutant spindle cell/sclerosing rhabdomyosarcomas: a clinicopathological and molecular comparison of mutated and non-mutated cases.
Cases were wild type for MYOD1 and no other mutations or rearrangements characteristic of a known subtype of rhabdomyoma or rhabdomyosarcoma were identified.
High MyoD1 expression (≥51% tumor cells) was seen in more cases of pure sclerosing, combined with spindle cell/sclerosing RMSs (10/10, 100%), as compared to the other subtypes (91/141, 67.4%) (p = 0.032).
Our data support unappreciated and dominant oncogenic roles for MYF5 and MYOD convergence on common transcriptional targets to regulate human RMS growth.
Clinically, a striking correlation was found between MYOD1 mutation and the clinical outcomes available for 15 of 21 cases: 5 of 7 patients with spindle cell and sclerosing rhabdomyosarcomas, harboring MYOD1 mutation, were alive-with-disease and 2 of 8 patients with spindle cell and sclerosing rhabdomyosarcomas, with mutant MYOD1, were free-of-disease.
A clinicopathologic study of head and neck rhabdomyosarcomas showing FOXO1 fusion-positive alveolar and MYOD1-mutant sclerosing are associated with unfavorable outcome.
Interestingly, biallelic IGF2 expression has been linked to rhabdomyosarcoma tumorigenesis and pUPD11 occurred in all 8 ERMS samples from CS individuals.