Evaluation of the clonal relationship between primary and metastatic renalcell carcinoma by comparative genomic hybridization

The outcome of patients with renal cell carcinoma is limited by the develop ment of metastasis after nephrectomy. To evaluate the genetic basis underly ing metastatic progression of human renal cell carcinoma in vivo, we perfor med a comparative genomic hybridization analysis in 32 clear-cell renal-cel l carcinoma metastases. The most common losses involved chromosomes 3p (25% ), 4q (28%), 6q (28%), 8p (31%), and 9p (47%). The most common gains were d etected at 17q (31%) and Xq (28%). There was one high-level gene amplificat ion at chromosome 11q22-23, The mean number of aberrations in lymph node (4 .8 +/- 2.8) and lung metastases (6.2 +/- 4.0) was lower than in other hemat ogenous metastases (11.5 +/- 8.7, P < 0.05), suggesting that hematogenous d issemination is linked to an acquisition of complex genomic alterations, As genetic differences between primary tumors and metastases give information on genetic changes that have contributed to the metastatic process, relati ve DNA sequence copy number changes in 19 matched tumor pairs were compared . Genomic changes, which frequently occurred in metastases but not in the c orresponding primary tumor were losses of 8p and 9p and gains of 17q and Xq . An abnormal function of genes in these regions may contribute to the meta static process. According to a statistical analysis of shared genetic chang es in matched tumor pairs, a high probability of a common clonal progenitor was found in 11 of 19 patients (58%). Six metastases (32%) were geneticall y almost completely different from the primary, suggesting that detection o f genomic alterations in primary tumors gives only a restricted view of the biological properties of metastatic renal cell carcinoma.