NOVEL VARIANTS OF HUMAN IFN-ALPHA DETECTED IN TUMOR-CELL LINES AND BIOPSY SPECIMENS

Interferon-alpha constitutes a complex gene family with 14 genes clust ered on the short arm of chromosome 9. More than 50 sequence variants have been described, However, an extensive genetic polymorphism has no t been seen in the few population studies reported so far, As many of the sequence variants reported were derived from tumor cell lines, we have investigated whether IFN-alpha genes are unstable in tumor cells, Using fluorescence-assisted mismatch analysis (FAMA), combined with a llele-specific primer extension, RFLP analysis, and direct sequencing, we detected in a panel of 14 tumor cell lines two new sequence varian ts of the IFNA1 and IFNA13 genes, Further two-paint mutations were fou nd in tumor samples from leukemias (n = 10) and renal cell carcinomas (n = 17) not seen in normal tissues, In the IFNA17 gene, three new seq uence variants were detected, one in a tumor cell line and two in tumo r biopsy specimens, Besides these individual point mutations, two new polymorphisms were found in each of the IFNA13 and IFNA17 genes, No ne w variants were found in the IFNA2 and IFNA10 genes, The results sugge st that new sequence variants of the IFN-alpha genes occur relatively frequently in tumors or in tumor cell lines.