DISTINCT REGIONS OF FREQUENT LOSS OF HETEROZYGOSITY OF CHROMOSOME 5P AND 5Q IN HUMAN ESOPHAGEAL CANCER

Loss of heterozygosity (LOH) studies reported thus far suggest that tu mor suppressor loci on chromosome 5q are important in esophageal cance r (EC) while little is known about the involvement of chromosome 5p. T o investigate the potential existence of tumor suppressor gene(s) on c hromosome 5 contributing to the development of EC, we performed LOH st udies using a total of 24 polymorphic markers spanning the entire chro mosome 5. Seventy primary esophageal cancers were microdissected and a llelic deletions were detected by polymerase chain reaction (PCR)-sing le strand conformation polymorphism or by microsatellite analysis. LOH was observed in at least I of the loci in 47 of 70 (67%) esophageal t umors. Initially, 40 tumors [24 squamous cell carcinomas (SCC) and 16 adenocarcinomas (ADC)], each with matched histologically normal esopha geal mucosa, were analyzed at 15 marker loci on 5p and 5q. A novel loc us, D5S667 on 5p15.2, exhibited the highest frequency of LOH (44%) in these tumors along with another previously reported region of frequent deletion, irf-1 (5q31.1). In a series of 30 additional EC tumors (I I SCC and 19 ADC), a detailed LOH analysis of chromosome 5p15.2 region was conducted using 10 additional polymorphic markers, which mapped th e Frequently deleted region within 1 cM. Overall, LOH at the D5S667 lo cus was observed more frequently in SCC than in ADC (62% vs. 23%, p = 0.01). This significant rate of LOH of a distinct region of chromosome 5p implicates the existence of a putative tumor suppressor gene locus involved in EC. (C) 1998 Wiley-Liss, Inc.