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The prevalence of HLA‐I LOH in Chinese pan‐cancer patients and genomic features of patients harboring HLA‐I LOH
Author(s) -
Zhao Jian,
Xiao Xiaoxiong,
Li Yue,
Gao Xuan,
Zhang Xiuqin,
Liu Zeyi,
Yi Yuting,
Fu Xiaorui,
Wang Han,
Guan Yanfang,
Xia Xuefeng,
Zhang Weixing,
Huang Jian'an
Publication year - 2021
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.24255
Subject(s) - biology , cancer , human leukocyte antigen , microsatellite instability , cancer research , lung cancer , population , genetics , immunology , gene , oncology , antigen , microsatellite , allele , medicine , environmental health
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.