Somatic genomic rearrangements in human leucocyte antigens region in solid ovarian tumors

Abstract

The success of immunotherapy for ovarian cancer is determined by the effectiveness of the patient’s immune response, as well as the qualitative and quantitative representation of antigens of the main histocompatibility complex in tumor cells and microenvironment. The level of the HLA (Human Leukocyte Antigens) genes expression in tumor tissue does not always correctly reflect the expression of these genes in different populations of tumor cells. Aim. To analyze the frequency and range of somatic deletions and duplications in the HLA locus. Methods. LOH-analysis (Loss of Heterozyhosity) of the STR-markers (Short Tandem Repeats) in the ovarian tumors of affected patients. Results. We have shown that complex somatic genomic reorganizations, involving several HLA loci, are quite common in ovarian tumors. The detected genetic alterations vary by both the type (deletions and mutations in STR alleles) and proportion of the sub-population of cells with the alterations. Conclusion. The results obtained allow us to propose the LOH-analysis for highly effective detection of aneuploidy and different types of somatic genomic reorganizations in the HLA region even in minor cell populations. This analysis provides the additional prognostic information for predic ting the effectiveness of different types of ovarian cancer immunotherapy at the indi vidual level.