Detection of Human Leukocyte Antigen Class I Loss of Heterozygosity in Solid Tumor Types by Next-generation DNA Sequencing

Detection of Human Leukocyte Antigen Class I Loss of Heterozygosity in Solid Tumor Types by Next-generation DNA Sequencing

PUBLICATIONS

November 6, 2019

Society for Immunotherapy of Cancer 2019, Tempus-authored — Human leukocyte antigen (HLA) class I proteins are expressed on the surface of all nucleated cells and are vital for immune surveillance. When tumor-specific mutations (neoantigens) are presented on HLA molecules to CD8+ T cells, this recognition can drive immune responses against the tumor and lead to tumor destruction. One mechanism of immune escape for tumors is loss of heterozygosity in HLA genes (HLA-LOH), which reduces the total number of neoantigens available for presentation to T cells. Due to the highly polymorphic nature of HLA, the copy number status of HLA genes is extremely challenging to assess by standard bioinformatics approaches. To investigate the prevalence of HLA-LOH, we developed a specialized pipeline to detect HLA-LOH by DNA next-generation sequencing (NGS).

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Authors: Jason Perera, Brandon Mapes, Denise Lau, Ameen Salahudeen, and Aly Khan