Immune recognition of cancers can be inhibited if the molecules that present cancer cell-specific antigens are disrupted. We have developed a tool that can detect four different types of disruption. Overall, we find that both genetic and non-genetic disruption of these molecules is common in lung and breast tumors.
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References
McGranahan, N. et al. Allele-specific HLA loss and immune escape in lung cancer evolution. Cell 171, 1259–1271.e11 (2017). This paper reports that 40% of lung tumors are disrupted through genomic changes.
GTEx Consortium et al. Genetic effects on gene expression across human tissues. Nature 550, 204–213 (2017). This paper gives an overview of the GTEx study, from which we used the lung and breast cohorts to study HLA variation in normal tissue.
Frankell, A. M. et al. The evolution of lung cancer and impact of subclonal selection in TRACERx. Nature 616, 525–533 (2023). This paper explores the tumor samples from 421 patients in the TRACERx lung cancer cohort, which we used to study HLA disruption in lung tumors.
The Cancer Genome Atlas Research Network et al. The Cancer Genome Atlas Pan-Cancer analysis project. Nat. Genet. 45, 1113–1120 (2013). This paper gives an overview of the TCGA study, from which we used the lung and breast cancer cohorts to study HLA disruption in tumors.
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This is a summary of: Puttick, C. et al. MHC Hammer reveals genetic and non-genetic HLA disruption in cancer evolution. Nat. Genet. https://doi.org/10.1038/s41588-024-01883-8 (2024).
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Genetic and non-genetic HLA disruption is widespread in lung and breast tumors. Nat Genet 56, 2008–2009 (2024). https://doi.org/10.1038/s41588-024-01886-5
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DOI: https://doi.org/10.1038/s41588-024-01886-5
