title: Integration of high-risk human papillomavirus DNA correlates with HLA genotype aberration and reduced HLA class I molecule expression in human cervical carcinoma.
abstract: In human cervical cancer (CC), local immunity against this human papilloma virus (HPV)-associated neoplasia has been signified. To stratify the possibility of HPV integration on HLA mutations, we measured the genotypic and phenotypic integrity of all available HLA class I loci in 30 cases of CC. Paired normal and cancer genomic DNA was analyzed with DNA typing trays, including 57 subtypes of HLA-A, 120 subtypes of HLA-B, and 60 subtypes of HLA-C. We demonstrated significant mutations of HLA genotype with reduced HLA molecule expression in CC. HPV coincide in > 70% cases of aberrant HLA genes. Southern blot analysis revealed the presence of HPV DNA within the mutated HLA foci. Our study reveals a plausible role of HPV integration in the contexts of aberrant HLA genotypes in CC cells. Disruptions of the HLA genes can be possible tactics of HPV to attain the potential carcinogenetic purposes, and thus the cancer immune escape.
authors.affiliation: Department of Obstetrics and Gynecology, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei 100, Taiwan.
authors.forename: Bor-Ching
authors.initials: BC
authors.lastname: Sheu
authors.forename: Shin-Heng
authors.initials: SH
authors.lastname: Chiou
authors.forename: Wen-Chun
authors.initials: WC
authors.lastname: Chang
authors.forename: Song-Nan
authors.initials: SN
authors.lastname: Chow
authors.forename: Ho-Hsiung
authors.initials: HH
authors.lastname: Lin
authors.forename: Ruey-Jien
authors.initials: RJ
authors.lastname: Chen
authors.forename: Su-Cheng
authors.initials: SC
authors.lastname: Huang
authors.forename: Hong-Nerng
authors.initials: HN
authors.lastname: Ho
authors.forename: Su-Ming
authors.initials: SM
authors.lastname: Hsu
mesh_terms: D002277:Carcinoma / Q000235:genetics* / Q000276:immunology / Q000821:virology*; D004279:DNA, Viral / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D005805:Genes, MHC Class I; D006680:HLA Antigens / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009154:Mutation; D027383:Papillomaviridae / Q000235:genetics*; D010641:Phenotype; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000276:immunology / Q000821:virology*; D016662:Virus Integration
chemical_list: D004279:DNA, Viral; D006680:HLA Antigens