© 1999 by Oxford University Press
Journal of the National Cancer Institute, Vol. 91, No. 19, 1669-1677,
October 6, 1999
© 1999 Oxford University Press
Human Leukocyte Antigen Class I Gene Mutations in Cervical Cancer
Affiliations of authors: L. A. Koopman, G. J. Fleuren (Department of Pathology), A. R. van der Slik, M. J. Giphart (Department of Immunohematology and Bloodbank), Leiden University Medical Center, The Netherlands.
Correspondence to: Louise A. Koopman, M.Sc., Department of Pathology, L1-Q/P1-40, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands (e-mail: L.A.Koopman{at}pathology.medfac.leidenuniv.nl).
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.
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