Here, we show that in hepatocellular carcinoma (HCC, the most prevalent form of primary liver cancer), tumours with a high burden of broad genomic alterations presented immune exclusion. On the other hand, HCC tumours with a reduced rate of broad genomic alterations were enriched in the HCC immune class, exhibited inflammatory traits and were cleared from CTNNB1 mutations. Overall, we propose that, in HCC, the acquisition of high-levels of broad copy number alterations might be implicated in the development of immune evasion, and that tumours presenting a reduced rate of these broad alterations display an immune profile which may indicate a favourable response to immunotherapies.
Overall design
Genomic DNA extracted from human hepatocellular carcinomas/adjacent tissues was genotyped using HumanOmniExpressExome-8v1_A (Illumina) To investigate the impact of the burdens of broad and focal copy-number alterations (CNAs) on the molecular and immune features of HCC, we conducted SNP array analysis (HumanOmniExpressExome-8v1_A from Illumina) on 150 HCC tumor samples and their corresponding non-tumour adjacent liver tissues. We used these data to compute CNA segments per sample and to generate scores capturing the burden of broad and focal CNAs (those spanning >=50% and <50% of a chromosome arm, respectively). We then evaluated differences in tumor molecular features associated with these scores (using already published mutation profiles, clinical and transcriptomic data).
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