C-HA-RAS-1 RESTRICTION-FRAGMENT-LENGTH-PO LYMORPHISM IN THE PATIENTS WITH MULTIPLE PRIMARY CANCERS AND NONSMALL CELL LUNG-CANCER

Restriction fragment length polymorphism in the human c-Ha-ras-1 locus , associated with a minisatellite sequence, was examined in 45 multipl e primary cancer (MPC) patients, 56 patients with squamous cell lung c ancer (SCLC), 21 patients with lung adenocarcinoma (LAC), and 53 indiv iduals having no oncopathology. Southern analysis of cellular DNA reve aled the presence of 4 common alleles (with collective allele frequenc y close to 94% in the control group) and a set of rare alleles. Allele a3, (2.1 kb in size under MspI/HpalI digestion) was shown to be more frequent in the MPC than in the control group. The same tendency was o bserved in the patients with highly differentiated cell lung cancer. A n increased frequency of the a4 allele (2.5 kb under MspI/HpaII digest ion) was observed in the patients with adenocarcinomas as well as in t he patients with metastases and low levels of tumor tissue differentia tion. The elevated frequencies of a3 in the MPC group and of a4 in the LAC patients did not correlate with increased risk of the cancers men tioned above but was associated with type of tumor progression. Previo usly, it was reported that the minisatellite sequence within the c-Ha- ras-I locus possesses enhancer activity. Our data indirectly confirm t he hypothesis that the efficiency of minisatellite modulator activity is associated with fragment size.