Mapping of genetic deletions on the long arm of chromosome 4 in human esophageal adenocarcinomas

Loss of the long arm of chromosome 4 has been identified previously as a co mmon occurrence in adenocarcinomas of the esophagus and gastroesophageal ju nction by relatively low resolution genetic surveys. To better define the e xtent of 4q deletion in these neoplasms we isolated DNA from 29 primary car cinomas using microdissection, and used DNA obtained from xenografts of 14 carcinomas grown in immunodeficient mice in an assay of loss of heterozygos ity of 25 polymorphic microsatellite markers distributed along the chromoso mal arm. Two carcinomas exhibited widespread microsatellite instability and were excluded from deletion mapping. In the remaining 41 carcinomas, loss of heterozygosity was detected in 33 (80%), Twenty-three cancers showed com plete or extensive reduction to homozygosity along the length of the long a rm. Ten cancers had smaller discrete areas of loss and were principally use ful in discerning three non-overlapping areas of con sensus genetic deletio n. Area 1 centered on marker D4S1534 at 4q21.1-22, area 2 centered on marke r D4S620 at 4q32-33, and area 3 centered on marker D45426 at 4q35, No known tumor suppressor genes map to these loci, but the frequent deletion of the se areas in gastroesophageal carcinomas and in other carcinomas suggests th at undiscovered tumor suppressor genes may reside here.