Genetic analysis of p73 localized at chromosome 1p36.3 in primary neuroblastomas.
BACKGROUND
Human p73, a novel homolog of p53, has recently been cloned and mapped at chromosome 1p36.3, the locus for putative tumor suppressor gene(s) of neuroblastoma (NBL) and other cancers. p73, like p53, inhibits growth and induces apoptosis in neuroblastoma and osteosarcoma cell lines.


METHODS
To test the hypothesis that p73 is a NBL suppressor gene, we examined expression, allelo-typing, and mutation of the p73 gene in primary human neuroblastomas. Loss of heterozygosity (LOH) for p73 was performed in 272 primary NBLs using a CT repeat polymorphic marker, which we found in intron 9 of the p73 gene.


RESULTS
p73 LOH was observed in 28 out of 151 (19%) informative cases. The high frequency of p73 LOH was significantly associated with sporadic neuroblastomas (P< 0.001), MYCN amplification (P< 0.001), and advanced stages (P< 0.05). Mutational analyses by PCR-SSCP (single strand conformation polymorphism) revealed two mis-sense mutations in 140 NBLs, one somatic and one germline.


CONCLUSIONS
Thus, the present results have shown that mutation of p73 is infrequent in NBLs, although the p73 locus is frequently lost in advanced stage tumors. These suggest that p73 may not be a tumor suppressor in the classic Knudson manner.
Ichimiya
S
S
Division of Biochemistry, Chiba Cancer Center Research Institute, Japan.
Nimura
Y
Y
Kageyama
H
H
Takada
N
N
Sunahara
M
M
Shishikura
T
T
Nakamura
Y
Y
Sakiyama
S
S
Seki
N
N
Ohira
M
M
Kaneko
Y
Y
McKeon
F
F
Caput
D
D
Nakagawara
A
A
D019943:Amino Acid Substitution; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics* / Q000648:ultrastructure; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D006801:Humans; D019656:Loss of Heterozygosity; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics; D009447:Neuroblastoma / Q000097:blood / Q000235:genetics* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins