P53 HOT-SPOT MUTATIONAL ANALYSIS IN ADVANCED WESTERN GALLBLADDER CARCINOMA

In gallbladder carcinoma, studies on the prime target of genetic alter ations and gene therapy in human gallbladder malignancies, the p53 tum or suppressor gene, have been focusing on this gene's immunohistochemi cal detection. From November 1991 to October 1993, seven patients suff ering from gallbladder carcinoma underwent surgical resection. Cancero us and normal liver tissues were obtained immediately after surgery, s nap-frozen in liquid nitrogen, and stored at -80 degrees C for immunoh istochemistry and DNA isolation. Exons 5, 6, 7, and 8 of the p53 gene were completely sequenced following polymerase chain reaction (PCR) am plification of a 1574-bp fragment. Missense mutations were detected in the cancerous tissues of two patients: one transition each on codons 134 (Phe--> Leu) and 146 (Trp--> Arg). Immunohistochemical p53 stainin g was positive in the latter patient only. This is the first report on sequence analysis and mutagenesis of the p53 gene in Caucasian patien ts with gallbladder cancer. Both mutations were transitions and seem t o represent a rather rare event. The possible impact of p53 mutagenesi s on gallbladder tumorigenesis requires evaluation in larger studies.