Molecular evidence for derivation of metastatic cells from minor subclonesof primary clear renal cell carcinomas

The production of metastases depends on changes in a large number of genes. It is also connected with the interaction of tumor cells with the environm ent. It has been reported that primary tumor clone domination is also an im portant factor in metastasizing,;md in many neoplasms dominating clones are the metastatic forerunners. Up to now it is unknown whether domination of a given clone in a primary renal cell carcinoma is a crucial factor in form ing metastases or rather presence or absence of specific genes imposes the major advantage in the metastatic process. To study the presence or absence of the duplication and mitotic nondisjunction event as one of the phenomen on in the creation of metastases, as well as possible derivation of metasta tic cells from the minor subclone of primary tumor, we examined three metas tatic renal clear-cell carcinomas in which by comparative genomic hybridiza tion we detected the loss of 3p in the primary tumor and two copies of 3p i n the corresponding metastasis. Loss of heterozygosity analyses using marke rs for 3p25 (D3S1038), 3p21.1 (D3S1295), and 3p14.2 (D3S1481) proved hetero zygosity of at least two 3p loci in all metastatic tumors, which indicates the absence of mitotic nondisjunction event as a cause of occurrence of two copies of 3p in metastases. Our results suggest that in some of the clear- cell renal carcinomas metastatic cells may derive from minor subclones of p rimary tumors.