title: The p73 gene is less involved in the development but involved in the progression of neuroblastoma.
abstract: We performed expression, mutation, loss of heterozygosity (LOH) and fluorescence in situ hybridization (FISH) analyses of the p73 gene in neuroblastomas (NBs). Reverse transcription-polymerase chain reaction (RT-PCR) using primers which can detect both the p73alpha and p73beta transcripts was performed on 30 fresh NBs and 22 NB cell lines. Aberrant expression of the p73 gene was found in 4 (25%) of 16 primary tumors found by mass screening and in 10 (71.4%) of 14 primary tumors found clinically. The rates of expression in these two types of tumors were significantly different (p=0.026, Fisher's exact test). The incidence of aberrant expression of the p73 gene was significantly higher in stage IV patients than in stages I, II, III plus IVS patients (p=0.0236, Fisher's exact test). No homozygous deletions or rearrangements of the p73 gene were found in any samples examined. In addition to the polymorphism in exon 2, a silent mutation (codon 336 GCC/GCT) was found in one primary tumor. LOH of the p73 gene was detected in 5 (15%) of 33 primary NBs using PCR-LOH analysis. FISH analysis showed that all 17 NB cell lines used in this study revealed allelic loss of the p73 gene, while most of them expressed the p73 gene. These results suggest that the p73 gene is not monoallelically expressed in NB. We conclude that the p73 gene is less involved in the development but involved in the progression of neuroblastoma.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: H W
authors.initials: HW
authors.lastname: Yang
authors.forename: H Y
authors.initials: HY
authors.lastname: Piao
authors.forename: Y Z
authors.initials: YZ
authors.lastname: Chen
authors.forename: J
authors.initials: J
authors.lastname: Takita
authors.forename: M
authors.initials: M
authors.lastname: Kobayashi
authors.forename: M
authors.initials: M
authors.lastname: Taniwaki
authors.forename: K
authors.initials: K
authors.lastname: Hashizume
authors.forename: R
authors.initials: R
authors.lastname: Hanada
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
authors.forename: T
authors.initials: T
authors.lastname: Taki
authors.forename: F
authors.initials: F
authors.lastname: Bessho
authors.forename: M
authors.initials: M
authors.lastname: Yanagisawa
authors.forename: Y
authors.initials: Y
authors.lastname: Hayashi
mesh_terms: D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000032:analysis; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D015870:Gene Expression; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D019656:Loss of Heterozygosity; D009447:Neuroblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D017354:Point Mutation; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
chemical_list: D017931:DNA Primers; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins