MOLECULAR-GENETIC ANALYSIS OF TISSUE INHIBITORS OF METALLOPROTEINASE-1 GENE IN KOREAN COLON-CANCER PATIENTS

Exons of Tissue inhibitors of metalloproteinase-1 (TIMP-1), a metastas is suppressor gene, were amplified by polymerase chain reaction, TIMP- 1 alleles were classified, and nucleotide changes between tumor tissue s and their normal counterparts were screened by SSCP in 11 Korean col on cancer patients. No mutational change between cancer tissues and th eir corresponding normal mucosas was observed. However, three distinct SSCP type alleles (named A, B, and C in this study) were detected in the exon spanning 56 carboxyl terminal amino acids and entire 3'-UT. S ubsequent sequence analysis revealed that the nucleotide sequence of t he B type allele was the same as the published sequence [Carmichael, D . P., Sommer A., Thompson, R C., Anderson, D. C, Smith, C. G., Welgus, H. G., and Stricklin, G. P. (1986) Proc. Natl. Acad. Sci. USA 83, 240 7-2411] but allele A showed a ''C'' to ''T'' transition in the 3'-UT r egion. Allele C demonstrated a ''T'' to ''C'' transition in the third base of amino acid 158, resulting in no amino acid change. To our know ledge, this is the first dissection of TIMP-1 alleles at the nucleotid e level. The relation between our typing and previous BglI RFLP allele typing [Aldred, M. A, and Wright, A. F. (1994) Mol. Cell. Probes 8, 3 33-334] was studied. Type B was most abundantly found (10 out of 15 x chromosomes), type C allele was the second (4 out of 15X chromosomes) and type A was most rarely found (1 out of 15X chromosomes) among Kore an colon cancer patients. Analysis of TIMP-1 alleles in healthy Korean s showed similar distribution pattern.