COMPLEX CHARACTERISTICS OF ALTERATIONS IN ONCOGENES HER-2 ERBB-2, HER-1/ERBB-1, HRAS-1, C-MYC, ANTIONCOGENES P53, RB-1, AND DELETIONS OF CHROMOSOME-17 LOCI IN COLORECTAL CARCINOMAS/

Specimens of DNA isolated from the cells of primary colorectal carcino mas (CRC) were examined for molecular-genetic alterations in a number of oncogenes and antioncogenes and for deletions of some chromosome 17 regions. Amplification of oncogene erbB-1 was found in 2 of 56 (4%) s pecimens, and amplification of erbB-2 in 4 of 62 (6%). No amplificatio n of oncogene c-myc was revealed in any of 67 CRCs. Loss of heterozygo sis (LH) of chromosome 11p (probe hras-1) was observed in 2 of 37 info rmative CRC specimens. Deletions of oncogene hras-1 alleles were not a ccompanied by point mutations in the ''hot'' codons (12th and 61st) of the remaining allele of this gene. Alleles A3 and A4 of the hras-1 on cogene were shown to be prevalent in CRC patients as compared with hea lthy donors. No gross structural alterations were found in antioncogen es rb-1 (41 cases) or p53 (62 cases). LH of chromosome 17p (probe ynz- 22) occurred in 15 of 26 (58%) CRC cases and of 17q (probe thh-59) in 4 of 16 (25%). Among 35 CRC cases only one point mutation was detected in the 175th codon of gene p53. Complex Southern blot analysis of the above molecular-genetic abnormalities in 40 CRC cases revealed altera tions in 23 cases (58%). No correlation could be established among any genetic alterations or with the clinical parameters of the tumors. Th e experimental data presented in this work contradict the widespread v iewpoint about the obligatory involvement of the p53 suppressor gene i n chromosome 17 deletions in CRC.