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 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.
Koopman
L A
LA
Department of Pathology , Leiden University Medical Center, The Netherlands. L.A.Koopman@pathology.medfac.leidenuniv.nl
van Der Slik
A R
AR
Giphart
M J
MJ
Fleuren
G J
GJ
D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D017931:DNA Primers; D005260:Female; D005805:Genes, MHC Class I / Q000235:genetics*; D005838:Genotype; D006801:Humans; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000235:genetics*
D017931:DNA Primers