SUPERIMPOSED HISTOLOGIC AND GENETIC-MAPPING OF CHROMOSOME-17 ALTERATIONS IN HUMAN URINARY-BLADDER NEOPLASIA

Multistep alterations of chromosome 17 in the progression of human uri nary bladder neoplasia were studied by superimposed histologic and gen etic mapping. The p53 gene was included in the analysis as a model tum or suppressor gene that is frequently involved in urothelial carcinoge nesis. The strategy provided a systematic approach to the study of mul tistep genomic alterations that occur as neoplasia progresses from pre cursor intraurothelial conditions to invasive cancer. This was accompl ished by sampling the entire mucosa of the organ and displaying micros copically identified invasive cancer and precursor conditions in the f orm of a histologic map. Subsequent isolation of DNA provided a set of samples in which the search for genetic alterations was performed and superimposed on the histologic map. This approach disclosed multifoca l allelic losses of chromosome 17 in the early preinvasive phases of u rothelial neoplasia. The alterations were predominantly confined to th e p12-13, q22-11 and q24-25 regions. Mutations and allelic losses of t he p53 gene were mapped to early preinvasive phases of urothelial neop lasia. The data provide detailed analysis of chromosome 17 allelic los ses that occur in the development and progression of urothelial neopla sia and represent the first step for genome-wide modeling of multistep human urothelial carcinogenesis.