Publication: Copy Neutral LOH Affecting the Entire Chromosome 6 Is a Frequent Mechanism of HLA Class I Alterations in Cancer
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Identifiers
Date
2021-10-09
Authors
Garrido, Maria Antonia
Perea, Francisco
Vilchez, Jose Ramon
Rodríguez, Teresa
Anderson, Per
Garrido, Federico
Ruiz-Cabello, Francisco
Aptsiauri, Natalia
Advisors
Journal Title
Journal ISSN
Volume Title
Publisher
MDPI
Abstract
Total or partial loss of HLA class I antigens reduce the recognition of specific tumor peptides by cytotoxic T lymphocytes favoring cancer immune escape during natural tumor evolution. These alterations can be caused by genomic defects, such as loss of heterozygosity at chromosomes 6 and 15 (LOH-6 and LOH-15), where HLA class I genes are located. There is growing evidence indicating that LOH in HLA contributes to the immune selection of HLA loss variants and influences the resistance to immunotherapy. Nevertheless, the incidence and the mechanism of this chromosomal aberration involving HLA genes has not been systematically assessed in different types of tumors and often remains underestimated. Here, we used SNP arrays to investigate the incidence and patterns of LOH-6 and LOH-15 in a number of human cancer cell lines and tissues of different histological types. We observed that LOH in HLA is a common event in cancer samples with a prevalence of a copy neutral type of LOH (CN-LOH) that affects entire chromosome 6 or 15 and involves chromosomal duplications. LOH-6 was observed more often and was associated with homozygous HLA genotype and partial HLA loss of expression. We also discuss the immunologic and clinical implications of LOH in HLA on tumor clonal expansion and association with the cancer recurrence after treatment.
Description
MeSH Terms
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Major Histocompatibility Complex::Genes, MHC Class I
Medical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Chromosome Aberrations::Chromosome Duplication
Medical Subject Headings::Anatomy::Cells::Cellular Structures::Chromosomes::Chromosomes, Mammalian::Chromosomes, Human::Chromosomes, Human, 6-12 and X::Chromosomes, Human, Pair 6
Medical Subject Headings::Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Cytokine-Induced Killer Cells::T-Lymphocytes, Cytotoxic
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation::Allelic Imbalance::Loss of Heterozygosity
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Glycoproteins::Membrane Glycoproteins::Histocompatibility Antigens Class I
Medical Subject Headings::Diseases::Neoplasms
Medical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy
Medical Subject Headings::Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biology::Genetics::Genomics
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Globulins::Serum Globulins::Beta-Globulins::beta 2-Microglobulin
Medical Subject Headings::Phenomena and Processes::Immune System Phenomena::Immune System Processes::Tumor Escape
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation::Allelic Imbalance::Loss of Heterozygosity
Medical Subject Headings::Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes::T-Lymphocyte Subsets::T-Lymphocytes, Cytotoxic
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Major Histocompatibility Complex::Genes, MHC Class I
Medical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Chromosome Aberrations::Chromosome Duplication
Medical Subject Headings::Anatomy::Cells::Cellular Structures::Chromosomes::Chromosomes, Mammalian::Chromosomes, Human::Chromosomes, Human, 6-12 and X::Chromosomes, Human, Pair 6
Medical Subject Headings::Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Cytokine-Induced Killer Cells::T-Lymphocytes, Cytotoxic
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation::Allelic Imbalance::Loss of Heterozygosity
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Glycoproteins::Membrane Glycoproteins::Histocompatibility Antigens Class I
Medical Subject Headings::Diseases::Neoplasms
Medical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy
Medical Subject Headings::Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biology::Genetics::Genomics
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Globulins::Serum Globulins::Beta-Globulins::beta 2-Microglobulin
Medical Subject Headings::Phenomena and Processes::Immune System Phenomena::Immune System Processes::Tumor Escape
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation::Allelic Imbalance::Loss of Heterozygosity
Medical Subject Headings::Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes::T-Lymphocyte Subsets::T-Lymphocytes, Cytotoxic
DeCS Terms
CIE Terms
Keywords
Cancer immune escape, HLA class I, Copy-neutral loss of heterozygosity (CN-LOH), Antigen presentation, Beta2-microglobulin, Cytotoxic T-cells, Cancer immunotherapy, Escape del tumor, Genes MHC clase I, Pérdida de heterocigosidad, Presentación de antígeno, Microglobulina beta-2, Linfocitos T citotóxicos, Inmunoterapia
Citation
Garrido MA, Perea F, Vilchez JR, Rodríguez T, Anderson P, Garrido F, et al. Copy Neutral LOH Affecting the Entire Chromosome 6 Is a Frequent Mechanism of HLA Class I Alterations in Cancer. Cancers. 2021 Oct 9;13(20):5046