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Complete remission is observed in less than half of hypermutated (HM) tumours after immune checkpoint blockade therapy, indicating that HM tumours are very heterogeneous. Thus, there is an urgent requirement to decipher the unknown intrinsic HM tumour subtypes. Statistical analysis was performed on somatic mutation data from 5519 tumours across 11 cancer types obtained from The Cancer Genome Atlas and 338 colorectal cancer (CRC) samples obtained from an Asian cohort. Samples with a tumour mutation burden >10 mut/Mb were classified as HM. A total of 1040 HM samples harbouring corresponding transcriptomes were used for non-negative matrix factorisation clustering. Tumour mutational burden, neoantigens, T cell receptor (TCR) diversity, stromal score and immune score were compared between the subtypes. HM tumours fell into three distinct immune subtypes: HM1, HM2 and HM3. HM3 tumours were correlated with increased CD8 T cell infiltration, high TCR diversity, a high immune score and prolonged survival. HM2 tumours were correlated with an abundant stromal component, epithelial–mesenchymal transition, TGFβ, angiogenesis hallmarks and poor outcomes. The infiltration of more CD8 T cells and increased chemokine expression in HM3 were validated in CRC by immunofluorescence. These findings will facilitate the development of a subtype-oriented therapy strategy to enhance the treatment effect in the near future. • HM tumours fell into three distinct immune subtypes: HM1, HM2 and HM3. • HM3 tumours were correlated with CD8 T cell infiltration and prolonged survival. • HM2 tumours were correlated with stromal infiltration, EMT and poor outcome. [ABSTRACT FROM AUTHOR]

The expression of long noncoding RNA (lncRNA) is thought to be more cell-type specific than the expression of protein-coding genes. However, the expression profile of individual cells regarding lncRNA remains to be elucidated. Here, we comprehensively investigated the pattern of lncRNA expression across five glioblastoma tumors (414 cells) and two cell lines (GBM6 and GBM8, 127 cells). We found that there were more than 1,000 lncRNAs that varied between any two cells and that there was frequent gain and loss of lncRNA expression during tumor cell proliferation, suggesting a great heterogeneity in lncRNA expression across different single cells in glioblastoma. [ABSTRACT FROM AUTHOR]