Topographical Distributions of Allelic Loss in Individual Non-Small-Cell Lung Cancers

Abstract

Non-small-cell carcinomas of the lung, especially adenocarcinomas, are characterized by a high degree of morphological heterogeneity. As carcinogenesis has been suggested to be a multistep process involving sequential accumulation of multiple genetic alterations, morphological heterogeneity may represent a cross-sectional view of genetic alterations within individual tumors. We therefore examined the topographical distribution of loss of heterozygosity (LOH) events within 10 non-small-cell lung cancers to investigate whether, and which, genetic alterations are accumulated in relation to morphological progression. LOH at the TP53, 17p13.3, and 3p loci was detected in six, eight, and six of 10 informative cases, respectively. In each case, all portions of the tumor shared concordant LOH despite morphological diversity. In contrast, distributions of LOH at 2q, 9p, and 22q, which have been reported to be associated with the advanced stages of tumors, were divergent in two of three, four of eight, and one of one cases with LOH, respectively. In these cases, presence of LOH was mostly related to the morphological tumor grades. These findings suggest the accumulative feature of genetic alterations in particular loci that can be seen even in individual tumors. Furthermore, the present study indicated that cross-sectional examination of individual tumors is also important for better understanding of molecular pathogenesis of lung cancers.