LOSS OF NM23 AND ALU DNA IN HUMAN LUNG-CANCER PROPAGATED IN NUDE-MICE

Freshly resected human non-small cell lung cancer (NSCLC) has been suc cessfully transplanted and propagated subcutaneously in nude mice (Can cer Letters 61 (1991) 53-60). We used this model to study the changes of the human metastasis suppressor genes, nm23-H1 and nm23-H2, through the process of propagation and metastasis of human NSCLC. Using a non -radioisotopic Southern analysis, the nm23-H1 and nm23-H2 genes were d etected without evidence of deletion in the early generations of the t umor grafts. These genes, however, were absent from the tumor grafts s ampled past 4 generations of propagation and from all the propagated m etastases originated from the subcutaneous grafts. Further restriction analysis revealed that only mouse DNA, but no human Alu DNA, was pres ent in the tumor specimens which lacked the human nm23 genes. Thus, th ere is a loss of human DNA but a gain of mouse DNA in the propagated t umors originated from the transplanted human NSCLC. The mechanisms of loss of human DNA in these propagated tumors in nude mice have yet to be delineated.