Genetic abnormalities involved in the pathogenesis of gallbladder carcinoma

While considerable progress has been made in the understanding of the genetic changes involved in the pathogenesis of several human neoplasms, there is limited information about the genetic changes involved in the development of gallbladder carcinoma. Several studies indicate that TP53 (17p13) and p16(Ink4)/CDKN2 (9p21-22) gene loci abnormalities are frequent and early events in the pathogenesis of this neoplasm, in some cases preceding the onset of histological changes of invasion. Preliminary data also suggest that deletions at other chromosomal regions (8p21 and DCC at 18q21 loci) may play an important role in the development of gallbladder carcinoma; however, they need to be further analyzed. K-ras gene mutations appear to be an infrequent event in this neoplasm, except in gallbladder carcinomas associated with congenital abnormalities of the biliary tract. Genetic studies confirm that the sequence dysplasia-carcinoma in situ (CIS) is the usual route for the development of gallbladder carcinoma, and our recent data strongly suggest that adenomas are not precursors of this neoplasm.