Human Leukocyte Antigen Class I Gene Mutations in Cervical Cancer

• Published in: JNCI : Journal of the National Cancer Institute Vol. 91; no. 19; pp. 1669 - 1677
• Main Authors: Koopman, Louise A., van der Slik, Arno R., Giphart, Marius J., Fleuren, Gert Jan
• Format: Journal Article
• Language: English
• Published: Cary, NC Oxford University Press 06.10.1999; Oxford Publishing Limited (England)
• Subjects: Biological and medical sciences; Cervical cancer; Chromosomes, Human, Pair 6 - genetics; DNA Primers; Female; Female genital diseases; Genes; Genes, MHC Class I - genetics; Genotype; Gynecology. Andrology. Obstetrics; Humans; Leukocytes; Medical research; Medical sciences; Mutation; Phenotype; Polymerase Chain Reaction - methods; Tumor Cells, Cultured; Tumors; Uterine Cervical Neoplasms - genetics; Human; Polymerase chain reaction; HLA-System; Female; Genetics; Uterine cervix; Malignant tumor; Molecular biology; Uterine cervix diseases; Female genital diseases
• ISSN: 0027-8874; 1460-2105
• DOI: 10.1093/jnci/91.19.1669

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 have 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.