Molecular cytogenetic evaluation of gastric cardia adenocarcinoma and precursor lesions

Analyses of cancer incidence data in the United States and Western Europe r evealed steadily rising rates over the past decades of adenocarcinomas of t he esophagus and gastric cardia. Genetic information on gastric cardia aden ocarcinoma and its preneoplasias is sparse. We have used comparative genomi c hybridization to obtain a genome-wide overview of 20 archival gastric car dia adenocarcinomas and 10 adjacent preneoplastic lesions (4 metaplasias, 1 low-grade dysplasia, 5 high-grade dysplasias). Multiple genetic alteration s were discriminated in all adenocarcinomas. Frequent loss (greater than or equal to 25% of all tumors) was detected, in decreasing order of frequency , on 5q, 18q, 4q, 3p, 9p, 2q, 11q, 14q, 21q, 4p, 9q, 16q, 1p, and 8p. Frequ ent gain (greater than or equal to 25% of all tumors) was disclosed, in dec reasing order of frequency, on 20q, 7p, 8q, 1q, 7q, 20p, 17q, 13q, Xp, 6q, 8p, 19q, 5p, 6p, and Xq. Loss of the Y chromosome was found in 60% of male cases. High level amplification was frequently (>10% of all tumors) detecte d on 7q21, 8p22, 12p11.2, 17q12-q21, and 13q13.1-q13.2. The precursor lesio ns showed multiple aberrations in ah high-grade dysplasias, whereas few gen etic changes were discerned in LGD and metaplasias. High level amplificatio ns were also found in high-grade dysplasias, ie, on 7q21, 8p22, and 17q12-q 21. Moreover, the percentage of aberrations was not significantly different for invasive carcinomas or high-grade dysplasias. Approximately 70% of the precursor aberrations were also present in the adjacent carcinoma Minimal overlapping regions in the preneoplasias included loss on 18q12-q21 and gai ns on 8q23 and 17q12-q21, suggesting involvement of genes residing in these regions. In conclusion, we have (i) created a map of genetic alterations i n gastric cardia adenocarcinomas and (ii) provided evidence for the presenc e of a metaplasia-dysplasia-carcinoma sequence in this poorly understood ty pe of cancer.