Mutational analysis of the p73 gene localized at chromosome 1p36.3 in colorectal carcinomas.
Genetic alteration of p53, which monitors DNA damage and operates cellular checkpoints, is a major factor in the development of human colorectal carcinoma (CRC). Recently, p73, a novel family member of p53, has been identified and found, like p53, to activate p21Waf1/Cip1 and to induce apoptosis. The p73 gene was mapped at chromosome 1p36.3 which is a region frequently deleted in CRCs and other cancers including neuroblastoma. To assess whether or not p73 is a tumor suppressor gene of CRC, we performed mutational analysis of p73 in 82 colorectal tumor tissues paired with constitutional DNA. Using a microsatellite marker for p73, the loss of heterozygosity (LOH) study was performed and allelic loss of p73 was found in 17% of the CRCs. RT-PCR single strand conformation polymorphism analysis showed no mutation except three polymorphisms in the p73 coding region. In addition, p73 was expressed at higher levels in the CRC tissues than in the normal mucosa or neuroblastoma tissues, though the transcripts were detectable only by the RT-PCR method. Our results suggest that, in CRCs, p73 may not play a role as a tumor suppressor, at least not in a classic Knudson manner.
Division of Biochemistry, Chiba Cancer Center Research Institute, Chuoh-ku, Chiba 260-8717, Japan.
M
M
Sunahara
S
S
Ichimiya
Y
Y
Nimura
N
N
Takada
S
S
Sakiyama
Y
Y
Sato
S
S
Todo
W
W
Adachi
J
J
Amano
A
A
Nakagawara
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002878:Chromosomes, Human, Pair 1; D015179:Colorectal Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D016147:Genes, Tumor Suppressor; D016158:Genes, p53; D006801:Humans; D019656:Loss of Heterozygosity; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D014158:Transcription, Genetic
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins