Unknown primary tumors: establishment of cell lines, identification of chromosomal abnormalities, and implications for a second type of tumor progression

Abstract

We describe the establishment of two human unknown primary tumor (UPT) cell lines and a comparison of their cytogenetic properties with two direct harvests from two tumor biopsy specimens. Histopathological analysis of all four tumor specimens revealed them to be undifferentiated adenocarcinomas of unknown origin. The chromosome numbers in these samples vary between 38 and 144. Consistent structural anomalies involving chromosome 1 were observed in all cases. These included a deletion of the short arm (4 of 4), duplication of 1q (3 of 4) and the presence of homogeneously staining region (2 of 4). Several additional chromosomal changes involving chromosomes 7, 8, and 9 were also observed, but these were less consistent and their importance is not yet clear. Abnormalities in chromosome 1 have generally been associated with advanced malignancy. The finding of consistent chromosome 1 changes in UPT supports our hypothesis that these are type 2 progressors in that benign or less malignant stages are not readily identified. In short, UPT are likely malignant soon after transformation occurs, and this is reflected in their rapid acquisition of the metastatic phenotype and abnormalities in chromosome 1. We are therefore characterizing a number of additional UPT cases to determine if chromosome 1 and other cytogenetic changes are consistently associated with this unique subgroup of tumors.