COMPARISON OF DNA GAINS AND LOSSES IN PRIMARY RENAL CLEAR-CELL CARCINOMAS AND METASTATIC SITES - IMPORTANCE OF 1Q AND 3P COPY NUMBER CHANGES IN METASTATIC EVENTS

Archival material from primary and metastatic renal clear cell carcino mas of 25 patients was studied by comparative genomic hybridization, C opy number changes of entire chromosomes or chromosomal subregions wer e detected in 22 primary and 21 metastatic tumors, Copy number changes affected the following chromosomes in at least 20% of the 25 primary tumors (minimal common region given in parentheses): gains were noted for chromosomes 1 (1q21-->q23), 5 (5q31-->q34), 7 (7p), 8 (8q), 16 (16 p), 17 (17q12-->qter), 19, and 22 (22q12-->qter); losses were revealed for chromosomes 3 (3p21-->pter), 8 (8p23-->pter), 14 (14q21-->qter), and Y. The same chromosomal regions that were involved in primary rena l clear cell carcinomas were also found in the respective metastatic t umors but with strikingly different frequencies for a few regions, Met astatic tumors showed a significantly higher frequency of complete or partial gains of the long arm of chromosome 1, in particular at 1q21-- >q23 than primary tumors (16 cases versus 6 cases; P < 0.005). These d ata suggest a correlation of metastatic events in renal clear cell car cinomas with an increase in the copy number of genes located at 1q, in particular at 1q21-->q23, In contrast, the entire or partial loss of the short arm of chromosome 3 was significantly less frequent in metas tatic tumors (8 cases versus 15 cases; P < 0.025), The validity of 1q and 3p copy number changes detected by comparative genomic hybridizati on was confirmed by interphase cytogenetics with region-specific yeast artificial chromosomes to paraffin-embedded tumor tissue sections.