title: Human leukocyte antigen class I gene mutations in cervical cancer.
abstract: 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.
authors.affiliation: Department of Pathology , Leiden University Medical Center, The Netherlands. L.A.Koopman@pathology.medfac.leidenuniv.nl
authors.forename: L A
authors.initials: LA
authors.lastname: Koopman
authors.forename: A R
authors.initials: AR
authors.lastname: van Der Slik
authors.forename: M J
authors.initials: MJ
authors.lastname: Giphart
authors.forename: G J
authors.initials: GJ
authors.lastname: Fleuren
mesh_terms: 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*
chemical_list: D017931:DNA Primers