Infrequent somatic mutations of the p73 gene in various human cancers.
OBJECTIVE
It has already been reported that loss of heterozygosity (LOH) on chromosome 1p is frequent in a variety of human cancers. This finding implies the presence of some important tumour suppressor genes in this region. p73, a candidate tumour suppressor gene identified recently in chromosome band 1p36.33, encodes a protein highly homologous to p53. To investigate the role of the p73 gene in human carcinogenesis, we studied genetic alterations of this gene in various human cancers.


METHODS
We analysed the entire coding exons as well as their surrounding exon-intron boundaries of the p73 gene in 185 cases of various types of tumours (47 breast cancers, 43 colorectal cancers, 31 gastric cancers, 23 neuroblastomas, 21 lung cancer cell lines, and 20 pancreatic cancer cell lines); they are known as a group of tumours with frequent LOHs in the 1p region. PCR-SSCP analysis was performed and tumours in which aberrant migrating sized bands were observed were subjected to direct sequencing analyses.


RESULTS
Of the 185 cases, only one somatic mis-sense mutation of glutamine from arginine at codon 269 in exon 7 was found in one breast cancer. In addition, several polymorphisms were found at codons 137, 336, 349, and 610, as well as in introns 6, 8, and 9. Monoallelic expression was also observed in pancreatic cancer cell lines.


CONCLUSIONS
Our results suggest that inactivation of the p73 gene does not play a major role in the tumour types analysed in the present study.
Han
S
S
Department of Molecular Pathology, Tohoku University School of Medicine, Sendai, Japan.
Semba
S
S
Abe
T
T
Makino
N
N
Furukawa
T
T
Fukushige
S
S
Takahashi
H
H
Sakurada
A
A
Sato
M
M
Shiiba
K
K
Matsuno
S
S
Nimura
Y
Y
Nakagawara
A
A
Horii
A
A
D000483:Alleles; D001943:Breast Neoplasms / Q000235:genetics; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D004067:Digestive System Neoplasms / Q000235:genetics; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics; D020125:Mutation, Missense; D009369:Neoplasms / Q000235:genetics*; D009447:Neuroblastoma / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins