Copy Neutral LOH Affecting the Entire Chromosome 6 Is a Frequent Mechanism of HLA Class I Alterations in Cancer.

Autor: Garrido MA; Servicio de Radiología, UGC de Radiología, Hospital Virgen de la Nieves, 18014 Granada, Spain., Perea F; Servicio de Análisis Clínicos e Inmunología, UGC de Laboratorio Clínico, Hospital Universitario Virgen de las Nieves, 18014 Granada, Spain.; Instituto de Investigación Biosanitaria IBS.GRANADA, 18014 Granada, Spain., Vilchez JR; Servicio de Análisis Clínicos e Inmunología, UGC de Laboratorio Clínico, Hospital Universitario Virgen de las Nieves, 18014 Granada, Spain., Rodríguez T; Servicio de Análisis Clínicos e Inmunología, UGC de Laboratorio Clínico, Hospital Universitario Virgen de las Nieves, 18014 Granada, Spain.; Instituto de Investigación Biosanitaria IBS.GRANADA, 18014 Granada, Spain., Anderson P; Servicio de Análisis Clínicos e Inmunología, UGC de Laboratorio Clínico, Hospital Universitario Virgen de las Nieves, 18014 Granada, Spain.; Instituto de Investigación Biosanitaria IBS.GRANADA, 18014 Granada, Spain., Garrido F; Servicio de Análisis Clínicos e Inmunología, UGC de Laboratorio Clínico, Hospital Universitario Virgen de las Nieves, 18014 Granada, Spain.; Instituto de Investigación Biosanitaria IBS.GRANADA, 18014 Granada, Spain.; Departamento de Bioquímica, Biología Molecular III e Inmunología, Facultad de Medicina, Universidad de Granada, 18071 Granada, Spain., Ruiz-Cabello F; Servicio de Análisis Clínicos e Inmunología, UGC de Laboratorio Clínico, Hospital Universitario Virgen de las Nieves, 18014 Granada, Spain.; Instituto de Investigación Biosanitaria IBS.GRANADA, 18014 Granada, Spain.; Departamento de Bioquímica, Biología Molecular III e Inmunología, Facultad de Medicina, Universidad de Granada, 18071 Granada, Spain., Aptsiauri N; Instituto de Investigación Biosanitaria IBS.GRANADA, 18014 Granada, Spain.; Departamento de Bioquímica, Biología Molecular III e Inmunología, Facultad de Medicina, Universidad de Granada, 18071 Granada, Spain.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2021 Oct 09; Vol. 13 (20). Date of Electronic Publication: 2021 Oct 09.
DOI: 10.3390/cancers13205046
Abstrakt: 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.
Databáze: MEDLINE
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