Integration of high-risk human papillomavirus DNA correlates with HLA genotype aberration and reduced HLA class I molecule expression in human cervical carcinoma.
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.
Sheu
Bor-Ching
BC
Department of Obstetrics and Gynecology, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei 100, Taiwan.
Chiou
Shin-Heng
SH
Chang
Wen-Chun
WC
Chow
Song-Nan
SN
Lin
Ho-Hsiung
HH
Chen
Ruey-Jien
RJ
Huang
Su-Cheng
SC
Ho
Hong-Nerng
HN
Hsu
Su-Ming
SM
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
D004279:DNA, Viral; D006680:HLA Antigens