Novel variants of human IFN-alpha detected in tumor cell lines and biopsy specimens

Abstract

Interferon-alpha constitutes a complex gene family with 14 genes clustered on the short arm of chromosome 9. More than 50 sequence variants have been described. However, an extensive genetic polymorphism has not 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 allele-specific primer extension, RFLP analysis, and direct sequencing, we detected in a panel of 14 tumor cell lines two new sequence variants of the IFNA1 and IFNA13 genes. Further two-point mutations were found in tumor samples from leukemias (n = 10) and renal cell carcinomas (n = 17) not seen in normal tissues. In the IFNA17 gene, three new sequence variants were detected, one in a tumor cell line and two in tumor biopsy specimens. Besides these individual point mutations, two new polymorphisms were found in each of the IFNA13 and IFNA17 genes. No new variants were found in the IFNA2 and IFNA10 genes. The results suggest that new sequence variants of the IFN-alpha genes occur relatively frequently in tumors or in tumor cell lines.