BASE TRANSITIONS ARE THE MOST FREQUENT GENETIC CHANGES AT P53 IN GASTRIC-CANCER

We searched for P53 mutations in gastric carcinoma by analyzing tumor DNAs from 29 patients. We detected 13 different somatic mutations in 1 5 patients (52%) and a biallelic polymorphism in exon 6 (5 heterozygou s subjects). The somatic mutations were mainly localized in the sequen ces corresponding to the highly conserved domains of the protein. Twel ve samples showed a single base change: 11 missense and 1 nonsense mut ations. Three samples showed deletions leading to a frame shift, to th e in-frame loss of 2 amino acids, and to the deletion of a splicing si te. All point mutations, except one, were transitions, and 91% of them were G:C-->A:T changes. We previously analyzed this panel of tumors f or allelic loss at the 17p13 chromosomal region, where the P53 gene ha d previously been located: the results showed an increasing incidence of allelic loss in late-stage tumors. On the contrary, in the present study no trend between P53 mutations and tumor stages was found. This observation indicates that mutation events precede allelic loss in gas tric cancer. Half (54%) of the mutations occurred in samples without a llelic loss, suggesting that specific mutated alleles, acting in a dom inant negative fashion, can alter in vivo the P53 protein function.