RESUMO
Embryonal rhabdomyosarcoma (eRMS) shows the most myodifferentiation among sarcomas, yet the precise cell of origin remains undefined. Using Ptch1, p53 and/or Rb1 conditional mouse models and controlling prenatal or postnatal myogenic cell of origin, we demonstrate that eRMS and undifferentiated pleomorphic sarcoma (UPS) lie in a continuum, with satellite cells predisposed to giving rise to UPS. Conversely, p53 loss in maturing myoblasts gives rise to eRMS, which have the highest myodifferentiation potential. Regardless of origin, Rb1 loss modifies tumor phenotype to mimic UPS. In human sarcomas that lack pathognomic chromosomal translocations, p53 loss of function is prevalent, whereas Shh or Rb1 alterations likely act primarily as modifiers. Thus, sarcoma phenotype is strongly influenced by cell of origin and mutational profile.
Assuntos
Rabdomiossarcoma Embrionário/patologia , Sarcoma/patologia , Animais , Diferenciação Celular , Linhagem da Célula , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Genes do Retinoblastoma , Genes p53 , Humanos , Camundongos , Mutação , Receptores Patched , Receptor Patched-1 , Receptores de Superfície Celular/genética , Rabdomiossarcoma Embrionário/genética , Sarcoma/genéticaRESUMO
CONTEXT: Cribriform-morular variant of papillary thyroid carcinoma (CMVPTC) is one of the rare types of papillary carcinoma. It has been associated with familial adenomatous polyposis, though it can also occur sporadically. The molecular pathogenesis of this tumor is incompletely understood. It appears that there can be molecular contributions from the RET/PTC translocations and from mutations in the APC gene and beta-catenin gene, which are both part of the Wnt signaling pathway. However, one of the most common mutations in papillary carcinoma, the BRAF mutation, has not been reported in this variant of papillary carcinoma. OBJECTIVE: To investigate the BRAF mutational status in CMVPTC. DESIGN: Four cases of CMVPTC (1 associated with familial adenomatous polyposis and the others apparently sporadic) were identified from the files of 3 large centers. Deoxyribonucleic acid was extracted and successfully amplified from each case. The polymerase chain reaction products were sequenced and evaluated for the T1799A BRAF mutation. RESULTS: None of the 4 cases harbored the T1799A BRAF mutation (0/4). Conclusions.-The T1799A BRAF mutation does not appear to play a role in the tumorigenesis of CMVPTC.
