Genetic progression and heterogeneity in intraductal papillary-mucinous neoplasms of the pancreas

Abstract

Intraductal papillary-mucinous neoplasms (IPMNs) of the pancreas are ideal neoplasms to study clonal progression and genetic diversity because of their large size and prominent intraductal component. We microdissected 55 histologically defined areas from 13 IPMNs, extracted the DNA from each, and performed polymerase chain reaction (PCR)-based microsatellite analysis to detect loss of heterozygosity on chromosome arms 1p, 3p, 6q, 8p, 9p, 17p, 18q, and 22q. LOH was identified at 1p in two cases, at 3p in four cases, at 6q in seven cases, at 8p in four cases, at 9p in eight cases, at 17p in five cases, at 18q in five cases, and at 22q in one of the IPMNs examined. In one of the IPMNs, the allelic losses were uniform throughout multiple microdissected areas, and in four of the IPMNs, there was evidence of clonal progression. In contrast, in three of the IPMNs, substantial allelic heterogeneity was seen. This remarkable heterogeneity may, in part, be due to the slow growth rate of these neoplasms.