Multiple genetic alterations cause frequent and heterogeneous human histocompatibility leukocyte antigen class i loss in cervical cancer
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Authors
Koopman, Louise A.
Corver, Willem E.
Slik, Arno R. van der
Giphart, Marius J.
Fleuren, Gert Jan
Issue Date
2000-03-20
Type
Article
Language
en_US
Keywords
Cervix Neoplasms/Immunology , Genes , MHC Class I , DNA , Neoplasm/Genetics , Loss of Heterozygosity , Mutation
Alternative Title
Abstract
The nature and frequency of human histocompatibility leukocyte antigen (HLA) class I loss mechanisms in primary cancers are largely unknown. We used flow cytometry and molecular analyses to concurrently assess allele-specific HLA phenotypes and genotypes in subpopulations from 30 freshly isolated cervical tumor cell suspensions.
Tumor-associated HLA class I alterations were present in 90% of the lesions tested, comprising four altered pheno/genotype categories: (a) HLA-A or -B allelic loss (17%), mostly associated with gene mutations; (b) HLA haplotype loss, associated with loss of heterozygosity at 6p (50%). This category included cases with additional loss of a (third) HLA-A or -B allele due to mutation, as well as one case with an HLA class I–negative tumor cell subpopulation, caused by a β2-microglobulin gene mutation; (c) Total HLA class I antigen loss and retention of heterozygosity (ROH) at 6p (10%); and (d) B locus or HLA-A/B downregulation associated with ROH and/or allelic imbalance at 6p (10%). Normal HLA phenotypes and ROH at 6p were observed in 10% of the cases. One case could not be classified (3%).
Altered HLA class I antigen expression occurs in most cervical cancers, is diverse, and is mainly caused by genetic changes. Combined with widespread tumor heterogeneity, these changes have profound implications for natural immunity and T cell–based immunotherapy in cervical cancer.
Description
Citation
Koopman, L. A., Corver, W. E., van der Slik, A. R., Giphart, M. J., & Fleuren, G. J. (2000). Multiple genetic alterations cause frequent and heterogeneous human histocompatibility leukocyte antigen class I loss in cervical cancer. The Journal of experimental medicine, 191(6), 961–976. https://doi.org/10.1084/jem.191.6.961
Publisher
The Journal of Experimental Medicine