DETECTION OF CHROMOSOME 3P ALTERATIONS IN SERUM DNA OF NON-SMALL-CELLLUNG-CANCER PATIENTS

Background. The generally dismal outcome of non-small-cell lung cancer (NSCLC) is believed to be associated with the systemic nature of this disease. In current practice, the decision to begin adjuvant chemothe rapy in completely resected early stages is based on empirical criteri a and has not yet been influenced by the presence of individual risk f actors. Nonetheless, recent studies indicate that soluble tumor DNA is found in the serum and plasma of cancer patients, and microsatellite alterations have been identified in small-cell lung cancer and in head and neck neoplasms. Patients and methods. We have investigated serum DNA from 22 completely resected stage I-IIIA NSCLC patients using a po lymerase chain reaction microsatellite analysis with four microsatelli te markers at chromosome 3p (D3S1038, D3S1611, D3S1067 and D3S1284). R esults: Our analyses showed serum tumor DNA in 6 of 22 (28%) cases, wi th microsatellite alterations, either as a shift (changes in the size of the microsatellite sequence in the autoradiograph:) or as a loss of heterozygosity (LOH). LOH in both tumor and serum DNA at one or more microsatellite markers was found in four patients. Although it is stil l premature to look for prognostic implications, one patient with stag e I serum DNA was identified prior to the development of distant: meta stases. Conclusions. The findings suggest that detection of free circu lating DNA in sera of NSCLC patients is incidentally linked to the sys temic nature of lung cancer even at the earliest stage. These observat ions provide the first hint that serum tumor DNA is present in NSCLC p atients. The detection of DNA from cancer cells in the sera of NSCLC p atients could be useful for monitoring relapse in a relatively non-inv asive way, and the potential sensitivity of this test may help in sele cting candidates for adjuvant chemotherapy.