Genetic heterogeneity in patients with multiple neoplastic lung lesions: a report of three cases.

INTRODUCTION: It is important to determine the relation among the various lesions in patients presenting with multiple malignant lung tumors to define the best treatment approach. A better understanding of the molecular alterations present in the different lesions may help in defining this relation. METHODS: We performed a detailed molecular analysis of several tumor specimens obtained from three patients presenting with multiple lung lesions. Tumor specimens were analyzed for epidermal growth factor receptor (EGFR) and k-ras mutations by direct DNA sequencing. In addition, a genome-wide chromosomal copy number analysis was performed on DNA extracted from the various lesions using array-based comparative genomic hybridization. RESULTS: In one case, a deletion of 15 base pairs in exon 19 of EGFR was present in all tumor sites analyzed. Furthermore, a similar pattern of chromosomal aberrations was observed among the various lesions, suggesting that they share the same clonal origin. In the other two cases, in contrast, we identified distinct k-ras genotypes among the various lesions from the same patient. These lesions, moreover, showed different chromosomal aberration patterns, indicating that they may have different underlying pathways of tumorigenesis. CONCLUSION: Our results show that EGFR and k-ras mutation analysis, combined with chromosomal copy number profiling, can help in defining the relationship among different tumors in one patient.