title: Expression of the retinoblastoma susceptibility gene in childhood rhabdomyosarcomas.
abstract: BACKGROUND
  Alveolar and embryonal rhabdomyosarcomas are soft-tissue tumors that occur mainly in childhood. The more aggressive alveolar subtype has been found to possess a characteristic chromosomal abnormality located near the retinoblastoma susceptibility gene (RB1). RB1 is a tumor suppressor gene implicated in the development of retinoblastoma and other, unrelated malignancies, especially osteogenic sarcomas and other second malignancies in retinoblastoma survivors.
  
  
  OBJECTIVE
  The goals of our study were (a) to determine whether abnormalities of RB1 occur routinely in sporadic rhabdomyosarcomas, as reported for other sporadic malignancies, especially bone and soft-tissue sarcomas of adulthood; and (b) to assess differences in the functional status of the gene in embryonal and alveolar rhabdomyosarcomas that might explain the differing clinical aggressiveness of these two variants.
  
  
  METHODS
  Analyses of messenger RNA (mRNA) and protein expression and immunohistochemical studies were performed on 11 rhabdomyosarcoma cell lines from patients with no family history of retinoblastoma, and RB1 protein expression was studied by immunoprecipitation in primary tumor biopsy tissue from 18 patients with sporadic rhabdomyosarcoma (five embryonal and 13 alveolar).
  
  
  RESULTS
  The RB1 gene appears to be normal in structure, expression, and function and is comparably phosphorylated in both forms of childhood rhabdomyosarcoma. Normal-size RB1 mRNA was present in all rhabdomyosarcomas, whereas clearly abnormal expression was documented in the controls, as expected: mRNA transcripts were truncated in Y79 retinoblastoma and absent in DU4475 breast carcinoma. In addition, immunoprecipitation with antibody to RB1 protein indicated the presence of normal RB1 protein in all rhabdomyosarcomas.
  
  
  CONCLUSIONS
  These findings are distinct from those for other adult asarcomas, in which RB1 expression frequently is reported as abnormal. They are particularly surprising in view of the high incidence of RB1 abnormalities in osteosarcoma, the bone tumor most associated with retinoblastoma. The etiology and biologic behavior of rhabdomyosarcoma are, thus, unlikely to be dependent on RB1 mutations.
  
  
  CONCLUSIONS
  The findings reported here clearly imply that the RB1 gene is structurally and functionally normal in childhood rhabdomyosarcoma. Other, as yet unidentified, genetic defects are apparently etiologic in this particular sarcoma.
authors.affiliation: Department of Pathology and Laboratory Medicine, Childrens Hospital Los Angeles, CA 90027.
authors.forename: A
authors.initials: A
authors.lastname: De Chiara
authors.forename: A
authors.initials: A
authors.lastname: T'Ang
authors.forename: T J
authors.initials: TJ
authors.lastname: Triche
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics; D002648:Child; D005134:Eye Neoplasms / Q000235:genetics; D005260:Female; D005455:Fluorescent Antibody Technique; D016161:Genes, Retinoblastoma; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D012175:Retinoblastoma / Q000235:genetics; D016160:Retinoblastoma Protein / Q000096:biosynthesis / Q000235:genetics; D012208:Rhabdomyosarcoma / Q000235:genetics* / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016160:Retinoblastoma Protein