MICROSATELLITE ANALYSIS OF PLASMA DNA FROM PATIENTS WITH CLEAR-CELL RENAL-CARCINOMA

Deletions of DNA sequences on chromosome 3p [loss of heterozygosity (L OH)] are characteristic of clear cell renal carcinoma, which accounts for about 80% of all renal malignancies. Comparing tumor DNA to DNA fr om normal cells, LOH analysis of microsatellite sequences has aided in molecular diagnosis of renal carcinoma. Because clinically useful tum or markers do not exist for this cancer entity, the aim of the present study was to detect chromosome 3p microsatellite alterations (LOH and microsatellite instability) in plasma DNA from patients with clear ce ll renal carcinoma. Four chromosome 3p microsatellites (D3S1307, D3S15 60, D3S1289, and D3S1300) were amplified by fluorescent PCR using DNA isolated from normal blood cells and plasma of 40 patients. Correspond ing tumor DNA was available from 21 patients. Analyzing PCR products o n an automated DNA sequencer, we found LOH in at least one locus in 25 plasma samples (63%), and 14 plasma samples (35%) exhibited LOH at mo re than one locus. Microsatellite instability of plasma DNA was detect able in one patient (3%). No significant association of advanced (>T2N 0M0) tumor stages with LOH in plasma DNA could be demonstrated. If pre sent, modifications of plasma DNA and tumor DNA were identical. No alt erations of plasma DNA were found in healthy controls. Analysis of pla sma DNA from patients with clear cell renal carcinoma reveals tumor-sp ecific microsatellite alterations and may therefore have diagnostic po tential as a molecular tumor marker.