No abstract

The tumor suppressor gene APC was recently identified, and the cDNA was cloned from chromosome 5q21. Point mutations affecting APC are seen in the hereditary syndrome familial adenomatous polyposis, and point mutations in APC and a closely linked gene, MCC, as well as loss of heterozygosity involving chromosome 5q have been reported in sporadic colon cancer. To our knowledge, loss of heterozygosity involving APC or MCC or both has not yet been described in any other human cancer besides lung cancer. We used the polymerase chain reaction and DNA content flow cytometric nuclear sorting to examine 30 primary human esophageal cancers for loss of heterozygosity ofAPC or MCC or both. Loss of one allele was detected in 77% of 26 informative cases. These data suggest that loss of heterozygosity of regions on Sq including the APC and MCC genetic loci is involved in the development and/or progression of most human esophageal cancers.

No abstract

Loss of heterozygosity affecting chromosome 17p has been detected at high frequencies in a variety of human tumors, including cancers ofthe colon, breast, lung, and brain. One presumed target of these losses is p53, a tumor suppressor gene located on 17p. To our knowledge, loss of heterozygosityhas not yet been reported at any locus, including p53, in human esophageal cancer. Moreover, current methods of detecting loss of heterozygosity depend on the availability of large amounts of high molecular weight DNA, making the study of small biopsy specimens or paraffin-embedded tissues problematic. We examined 52 primary human esophageal neoplasms for loss of heterozygosity affecting the p53 gene by using the polymerase chain reaction. Loss of one allele was detected in 52% of informative cases and was more common in squamous carcinomas than in adenocarcinomas. Southern blot analysis was used to confirm polymerase chain reaction-derived data.The identification of allelic loss in approximately half of the tumors analyzed supports the hypothesis that inactivation of p53 is involved in the pathogenesis of esophageal cancer.Esophageal carcinoma is a major cancer worldwide, ranked among the leading causes of cancer death (1). There are two main forms of this disease, squamous cell carcinoma and adenocarcinoma. Squamous esophageal cancer is associated with ethanol and tobacco consumption (1), whereas primary esophageal adenocarcinoma usually accompanies Barrett esophagus (2). Barrett esophagus denotes replacement of the normal squamous esophageal lining by metaplastic columnar mucosa in response to chronic gastroesophageal reflux (3). Patients with this condition are at increased risk of developing esophageal adenocarcinoma (4, 5). Despite the clinical importance of esophageal cancer, its molecular basis is not well understood. Recent studies have addressed the role of ras family protooncogene activation in this disease, but ras mutations were found rarely or not at all (6-9). Amplification of several protooncogenes has also been reported (6, 10-13).Loss of heterozygosity (LOH) occurring frequently at a specific locus is widely assumed to imply the existence of a tumor suppressor gene at or near that locus. The p53 gene encodes an evolutionarily conserved 53-kDa cellular protein implicated in the control of cell proliferation and tumor formation/progression (14)(15)(16)(17)(18)(19)(20)(21)(22). LOH at or near the p53 gene locus, shown to occur frequently in a variety of human tumor types (18,(23)(24)(25)(26)(27)(28)(29), is believed to favor malignancy by removing a normal copy of this tumor suppressor gene (30). The remaining p53 allele is often inactivated by point mutation (18)(19)(20)(31)(32)(33)(34). It is believed that this mutant p53 may exert a dominant negative effect by complexing with wild-type product (35,36). A recent study suggests involvement of the p53 gene by point mutation in esophageal cancers (34). LOH at any locus, including 17p, has not to our knowledge been reported in esophageal cancer.Curren...