MUTATIONAL ANALYSIS OF THE P73 GENE LOCALIZED AT CHROMOSOME 1P36.3 INCOLORECTAL CARCINOMAS

Genetic alteration of p53, which monitors DNA damage and operates cell ular checkpoints, is a major factor in the development of human colore ctal carcinoma (CRC). Recently, p73, a novel family member of p53, has been identified and found, like p53, to activate p21(Wafl/Cipl) and t o induce apoptosis. The p73 gene was mapped at chromosome 1p36.3 which is a region frequently deleted in CRCs and other cancers including ne uroblastoma. To assess whether or not p73 is a tumor suppressor gene o f 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 alle lic loss of p73 was found in 17% of the CRCs. RT-PCR single strand con formation polymorphism analysis showed no mutation except three polymo rphisms in the p73 coding region. In addition, p73 was expressed at hi gher levels in the CRC tissues than in the normal mucosa or neuroblast oma 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.