RT Journal Article
T1 Copy Neutral LOH Affecting the Entire Chromosome 6 Is a Frequent Mechanism of HLA Class I Alterations in Cancer.
A1 Garrido, Maria Antonia
A1 Perea, Francisco
A1 Vilchez, Jose Ramon
A1 Rodríguez, Teresa
A1 Anderson, Per
A1 Garrido, Federico
A1 Ruiz-Cabello, Francisco
A1 Aptsiauri, Natalia
K1 HLA class I
K1 antigen presentation
K1 beta2-microglobulin
K1 cancer immune escape
K1 cancer immunotherapy
K1 copy-neutral loss of heterozygosity (CN-LOH)
K1 cytotoxic T-cells
AB 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.
SN 2072-6694
YR 2021
FD 2021-10-09
LK https://hdl.handle.net/10668/26347
UL https://hdl.handle.net/10668/26347
LA en
DS RISalud
RD Apr 5, 2025