The prevalence of HLA-I LOH in Chinese pan-cancer patients and genomic features of patients harboring HLA-I LOH

Hum Mutat. 2021 Oct;42(10):1254-1264. doi: 10.1002/humu.24255. Epub 2021 Jul 20.


HLA-I LOH may facilitate immune evasion. However, large population studies on the prevalence of HLA-I LOH across different cancer types and in relation to mutational profiles are lacking, in particular, in the Chinese population. In this study, analysis was performed in 1504 advanced pan-cancer patients and 134 early-stage non-small-cell lung cancer patients using a 1021-gene panel. The consistency between the 1021-gene panel and whole-exome sequencing was evaluated in 45 samples, where concordant results were obtained in 95.6% (43/45) of the samples. Analytical results revealed that the prevalence of HLA-I LOH in tumor tissue presents considerable differences across cancer types. HLA-I LOH was relevant to genomic instability, reflected in higher tumor mutation burden level. HLA-I LOH occurs more frequently in MSS samples than in MSI-H samples. The alteration frequencies of p53 pathway, RTK/RAS pathway, Notch pathway, Hippo pathway, and Nrf2 pathway in HLA-I LOH group were significantly higher than that in HLA-I stable group (p < .0001, p < .0001, p = .032, p = .013, p = .003, respectively). In DNA damage response pathways, alterations in the checkpoint factor pathway and Fanconi anemia pathway are enriched in HLA-I LOH group (p < .0001, p = .023, respectively). Besides, HLA-I LOH was accompanied by higher mutation rates of several tumor suppressors, including TP53 and LRP1B. These results may shed light on follow-up tumor immunology research.

Keywords: DNA damage response system; genomic instability; human leukocyte antigen complex; immunotherapy; loss of heterozygosity in HLA-I; oncogenic signaling pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Non-Small-Cell Lung*
  • China / epidemiology
  • Genomics
  • Humans
  • Loss of Heterozygosity
  • Lung Neoplasms* / epidemiology
  • Lung Neoplasms* / genetics
  • Prevalence