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

Total or partial loss of 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 class I genes are located. There is growing evidence indicating that LOH in contributes to the immune selection of loss variants and influences the resistance to immunotherapy. Nevertheless, the incidence and the mechanism of this chromosomal aberration involving 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 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 genotype and partial loss of expression. We also discuss the immunologic and clinical implications of LOH in on tumor clonal expansion and association with the cancer recurrence after treatment.