title: p53 gene gets altered by various mechanisms: studies in childhood sarcomas and retinoblastoma.
abstract: BACKGROUND
  Somatic and constitutional mutation screening of p53 in childhood sarcomas and retinoblastoma was investigated by a multitechnical approach to evaluate its role in the development/progression by somatic mutation events and/or genetic predisposition.
  
  
  METHODS
  The studies were carried out on a cohort of 100 sarcoma cases, i.e. Ewing's sarcoma (n=44), osteosarcoma (n=36), and rhabdomyosarcoma (n= 20), and on 50 retinoblastoma (Rb) cases.
  
  
  RESULTS
  Constitutional allelic deletion was found by FISH in 4% of sarcoma cases. Overall, 20% of sarcoma tumors showed p53 rearrangement by PCR/SSCP and Southern blot. Allelic deletion of p53 was detected in 78% of sarcoma and 55% of Rb tumors. p53 protein expression was detected by immunohistochemistry in 20% of sarcoma tumors.
  
  
  CONCLUSIONS
  This study for the first time provided evidence of p53 alteration through allelic deletion that are common primary somatic mutation events which occur irrespective of grade and stage and are hence probably associated with an early phase of tumorigenesis and/or tumor progression. The studies also explored the occurrence of de novo constitutional deletion of p53 in sporadic childhood sarcomas. This study in retinoblastoma provided evidence for the synergistic role of RB1 and p53, probably essential for the full-blown development of malignancy.
authors.affiliation: Cancer Cytogenetics Laboratory, Tata Memorial Hospital, Mumbai, India.
authors.forename: Prachi
authors.initials: P
authors.lastname: Ghule
authors.forename: Pratibha Amare
authors.initials: PA
authors.lastname: Kadam
authors.forename: Nirmala
authors.initials: N
authors.lastname: Jambhekar
authors.forename: Mikhil
authors.initials: M
authors.lastname: Bamne
authors.forename: Suresh
authors.initials: S
authors.lastname: Pai
authors.forename: Chandrika
authors.initials: C
authors.lastname: Nair
authors.forename: Shripad
authors.initials: S
authors.lastname: Banavali
authors.forename: Ajay
authors.initials: A
authors.lastname: Puri
authors.forename: Manish
authors.initials: M
authors.lastname: Agarwal
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D001859:Bone Neoplasms / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D017931:DNA Primers / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D018628:Gene Dosage; D016158:Genes, p53; D018095:Germ-Line Mutation; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D012516:Osteosarcoma / Q000235:genetics; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D019572:Retinal Neoplasms / Q000235:genetics*; D012175:Retinoblastoma / Q000235:genetics*; D012208:Rhabdomyosarcoma / Q000235:genetics; D012509:Sarcoma / Q000235:genetics*; D012512:Sarcoma, Ewing / Q000235:genetics
chemical_list: D017931:DNA Primers