Losses of heterozygosity on chromosomes 17p and 9p/18q my play important roles in early and advanced phases of gallbladder carcinogenesis

Purpose: This present study aimed to investigate the genetic changes in gal lbladder carcinogenesis. Methods: Eleven intramucosal gallbladder carcinoma s were compared with 31 invasive lesions for loss of heterozygosity (LOH) o n chromosomes 5q, 9p, 17p and 18q, frame-shift mutations in a ten-adenine r epeat site within the gene encoding the transforming growth factor beta typ e II receptor (TGF beta RII) and an eight-guanine repeat site within BAX, a nd point mutations in codon 12 of Ki-ras. Results: The incidences of LOH in intramucosal and invasive carcinomas were 14% and 17% on 5q, 9% and 52% on 9p, 64% and 65% on 17p, and 13% and 32% on 18q. No frame-shift mutations w ere found at TGF beta RII or BAX, and point mutations in codon 12 of Ki-ras were present in only 8% of the samples. Thus, LOH on 17p was by far the mo st frequent lesion with similar results in both intramucosal and invasive c arcinomas. In contrast, the frequency of LOH on 9p and 18q was distinctly h igher in invasive lesions. Conclusion: The present data suggest that LOH on 17p may play an important role in the evolution of gallbladder carcinoma f rom a relatively early phase, while LOH on 9p and 18q may play roles in pro gression.