PRIMARY SMALL-CELL LUNG CARCINOMAS AND THEIR METASTASES ARE CHARACTERIZED BY A RECURRENT PATTERN OF GENETIC ALTERATIONS

Small-cell lung cancer (SCLC) represents a group of highly malignant t umors giving rise to early and widespread metastases. We used comparat ive genomic hybridization in autoptic tumor specimens from 10 patients to discover genetic alterations that are associated with tumor progre ssion and potentially with the metastatic phenotype. Ten primary SCLC and 16 corresponding metastases were investigated with a maximum of 4 tumors per case. Prevalent changes observed in more than 60% of the pr imary tumors and their metastases included deletions on chromosomes 3p , 4q, 5q, 10q, 13q and 17p, and DNA over-representations on chromosome s 3q and 5p. The number of common alterations in the primary tumors an d the related metastases outnumbered the differences, indicating a clo nal relationship. Within the lesions of the same patient, differences were found between the primary tumor and the metastases as well as bet ween metastases of distinct organ sites. However, no specific alterati on was significantly associated with the metastatic phenotype. We sugg est that the high malignancy of SCLC is defined by the above-mentioned pattern of aberrations. (C) 1997 Wiley-Liss, Inc,.