Comparative genomic hybridization of cancer of the gastroesophageal junction: Deletion of 14Q31-32.1 discriminates between esophageal (Barrett's) andgastric cardia adenocarcinomas

Incidence rates hale risen rapidly for esophageal and gastric cardia adenoc arcinomas. These cancers, arising at and around the gastroesophageal juncti on (GEJ), share a poor prognosis. In contrast, there is no consensus with r espect to clinical staging resulting in possible adverse effects on treatme nt and survival. The goal of this study Has to provide more insight into th e genetic changes underlying esophageal and gastric cardia adenocarcinomas. We have used comparative genomic hybridization for a genetic analysis of 2 8 adenocarcinomas of the GEJ. Eleven tumors were localized in the distal es ophagus and related to Barrett's esophagus, and 10 tumors were situated in the gastric cardia. The remaining seven tumors Here located at the junction and could not be classified as either Barrett-related. or gastric cardia. We found alterations in all 28 neoplasms. Gains and losses Here distinguish ed in comparable numbers. Frequent loss (greater than or equal to 25% of al l tumors) H-as detected, in decreasing order of frequency, on 4pq (54%), 14 q (46%). 18q (43%), 5q (36%), 16q (36%), 9p (29%), 17p (29%), and 21q (29%) . Frequent gain (greater than or equal to 25% of all tumors) was observed, in decreasing order of frequency, on 20pq (86%), 8q (79%), 70 (61%), 13q (4 6%), 12q (39%), 15q (39%), 1q (36%), 3q (32%), 5p (32%), 6p (32%), 19q (32% ), Xpq (32%), 17q (29%), and 18p (25%). Nearly all patients were male, and loss of chromosome Y was frequently noted (64%). Recurrent high-level ampli fications (>10%) of all tumors) Here seen at 8q23-24.1. 15q25, 17q12-21, an d 19q13.1. Minimal overlapping regions could be determined at multiple loca tions (candidate genes are in parentheses): minimal regions of overlap for deletions were assigned to 3p14 (FHIT, RCA1), 5q14-21 (APC, MCC), 9p21 (MTS 1/CDKN2), 14q31-32.1 (TSHR), 16q23, 18q21 (DCC, PI5) and 21q21. Minimal ove rlapping amplified sites could be seen at 5p14 (MLVI2), 6p12-21.1 (NRASL3), 7p12 (EGFR), 8q23-24.1 (MYC), 12q21.1, 15q25 (IGFIR), 17q12-21 (ERBB2/ HER 2-neu). 19q13.1 (TGFB1, BCL3, AKT2). 20p12 (PCNA), 20q12-13 (MYBL2, PTPN1), and Xq25. The distribution of the imbalances revealed similar genetic patt erns in the three GEJ tumor groups. Hoe ever, loss of 14q31-32.1 occurred s ignificantly more frequent in Barrett-related adenocarcinomas of the distal esophagus, than in gastric cardia cancers (P = 0.02). The unclassified, "p ure junction" group displayed an intermediate position, suggesting that the se may be in part gastric cardia tumors, whereas the others may be related to (short-segment) Barrett's esophagus. In conclusion, this study has, firs t, provided a detailed comparative genomic hybridization-map of GEJ adenoca rcinomas documenting new genetic changes, as well as candidate genes involv ed. Second, genetic divergence was revealed in this poorly understood group of cancers.