Identification of Tumor Suppressor Loci on the Long Arm of Chromosome 5 in Pulmonary Large Cell Neuroendocrine Carcinoma

Abstract

BACKGROUND: A recent cytogenetic analysis of non-small cell lung cancer revealed hot-spot regions for deletion on the long arm of chromosome 5 and suggested the existence of putative tumor suppressor genes in that region. However, similar studies on genetic alterations in large cell neuroendocrine carcinoma (LCNEC) have been very limited. To our knowledge, this is the first report to screen for the loss of heterozygosity (LOH) and to examine the location of putative tumor suppressor genes on chromosome 5q in LCNEC. OBJECTIVES: To identify tumor suppressor loci on chromosome 5q in LCNEC by microsatellite analysis. PATIENTS AND METHODS: Microsatellite instability and LOH in tumor and normal tissue samples from 13 patients with LCNEC, who had undergone surgical resections, were analyzed by polymerase chain reaction using a panel of 19 microsatellite DNA markers spanning chromosome 5q. RESULTS: LOH was found in all of the 13 tumors (100%) in at least one informative marker tested. The following four common minimally deleted regions were noticed on chromosome 5q: 5q14.3-q21.1; 5q22.2-q23.1; 5q23.3-q33.2; and 5q35.1-q35.2. Three of 13 individual tumors (23.1%) exhibited shifted bands for at least one of the tested microsatellite markers. Shifted bands occurred in 6 of 224 loci (2.7%) tested. CONCLUSION: These data suggest the presence of at least four tumor suppressor loci on chromosome 5q in LCNEC, and further investigations into cloning candidate tumor suppressor genes are warranted.