Human leukocyte antigen class I gene mutations in cervical cancer

Background: Various mechanisms contribute to the loss of human leukocyte antigen (HLA) class I expression that is frequently observed in cancers. Although some single allele losses hare been ascribed to mutations in HLA class I genes, direct evidence for this phenomenon in vivo is still lacking. Thus, we investigated whether HLA class I gene mutations could account for the loss of allele-specific expression in cervical carcinomas. Methods: We used polymerase chain reaction-based techniques, including sequencing, oligonucleotide hybridization, and microsatellite analysis, to identify HLA class I gene defects in two tumor-derived cell lines and to confirm the presence of these defects in the original tumors. Results: In one tumor, in exon 2 of the HLA-B15 gene, a four-nucleotide insertion resulted in a stop codon in exon 3, In the other tumor, in two duplicated copies of the HLA-A24 gene, single-point mutations resulted in stop codons in exons 2 and 5, Conclusions: To our knowledge, this is the first report of HLA class I gene mutations identified in primary tumors that lead to loss of allelic expression in tumor cells. Such tumor-specific mutations may permit the cell to escape HLA class I-restricted cytotoxic T-cell responses.