P300 GENE ALTERATIONS IN COLORECTAL AND GASTRIC CARCINOMAS

Colorectal tumors frequently have loss of heterozygosity on chromosome 22q, suggesting that inactivation of tumor suppressor gene(s) on 22q participates in the tumor development. Neurofibromatosis 2 (NF2) gene and E1A binding protein p300 gene, recently identified on 22q, are tho ught to be candidates for tumor suppressor genes. In this study, mutat ion of the NF2 gene in 59 colorectal carcinomas, and mutation of the p 300 gene in 27 colorectal and two gastric carcinomas, were analysed us ing PCR-SSCP, RT-PCR-SSCP and direct sequencing methods. Missense muta tions of p300 gene were detected in a colorectal carcinoma, and in a g astric carcinoma, though no mutation of NF2 gene was detected. Both p3 00 mutations were somatic and coupled to deletion of the second allele of the gene, which suggests inactivation of the p300 gene in these ca rcinomas. The mutations are located within the Cys/His-rich regions, w hich are assumed to play important roles in the function of p300. Thes e are the first cases in which p300 gene has been found to be altered in both alleles, suggesting that inactivation of the p300 gene may be involved in the development of carcinomas, and that this gene may be t he target of loss of 22q in carcinomas of the digestive tract.