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The prevalence of HLA-I LOH in Chinese pan-cancer patients and genomic features of patients harboring HLA-I LOH
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  • Jian Zhao,
  • Xiaoxiong Xiao,
  • Yue Li,
  • Xuan Gao,
  • Xiuqin Zhang,
  • Zeyi Liu,
  • Yuting Yi,
  • Xiaorui Fu,
  • Han Wang,
  • Yanfang Guan,
  • Xuefeng Xia,
  • Weixing Zhang,
  • Jian'an Huang
Jian Zhao
First Affiliated Hospital of Soochow University
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Xiaoxiong Xiao
Xiangya Hospital Central South University
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Yue Li
First Affiliated Hospital of Soochow University
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Xuan Gao
Geneplus-Beijing Institute
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Xiuqin Zhang
First Affiliated Hospital of Soochow University
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Zeyi Liu
First Affiliated Hospital of Soochow University
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Yuting Yi
Geneplus-Beijing Institute
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Xiaorui Fu
Geneplus-Beijing Institute
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Han Wang
Geneplus-Beijing Institute
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Yanfang Guan
Geneplus-Beijing Institute
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Xuefeng Xia
Geneplus-Beijing Institute
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Weixing Zhang
Xiangya Hospital Central South University
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Jian'an Huang
First Affiliated Hospital of Soochow University
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Abstract

Loss of heterozygosity in HLA-I (HLA-I LOH) may facilitate immune evasion. However, the large population study of HLA-I LOH in Chinese pan-cancer patients remains to be explored. In this study, analysis was performed in 1504 advanced pan-cancer patients and 134 early-stage NSCLC patients using a 1021-gene panel. The consistency between the 1021-gene panel and whole-exome sequencing (WES) 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 presents considerable differences across cancer types. HLA-I LOH was relevant to genomic instability, reflected in higher tumor mutation burden (TMB) level. The incidence of HLA-I LOH in MSS samples was significantly higher than that 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<0.0001, p<0.0001, p=0.032, p=0.013, p=0.003, respectively). In DNA damage response (DDR) pathways, alterations in CPF pathway and FA pathway are enriched in HLA-I LOH group (p<0.0001, p=0.023, 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 research.

Peer review status:IN REVISION

14 Feb 2021Submitted to Human Mutation
15 Feb 2021Assigned to Editor
15 Feb 2021Submission Checks Completed
01 Mar 2021Reviewer(s) Assigned
27 Mar 2021Review(s) Completed, Editorial Evaluation Pending
01 Apr 2021Editorial Decision: Revise Minor