Novel mutational landscapes and expression signatures of lung squamous cell carcinoma

Oncotarget
Donghai XiongMing You

Abstract

Lung squamous cell carcinoma (LUSC) is a major subtype of Non-Small Cell Lung Cancer. To increase our understanding of the LUSC pathobiology, we performed exome sequencing and RNA-seq in 16 murine carcinogen-induced LUSC tumors and 8 normal murine lung tissue samples. Additionally, we conducted single-cell RNA-seq on two independent tumors from the same murine model. We identified a list of 59 cancer genes recurrently mutated in the mice LUSC tumors, 47 (80%) of which were also mutated in human LUSCs. At the single cell level, we detected unique clonal mutation patterns for each of the two LUSC tumors, being initiated from clones carrying the mutantIgfbp7andTrp53genes, respectively. We also identified an expression signature serving as an effective classifier for LUSC tumors and a strong predictor of survival outcomes of lung cancer patients. Lastly, we found that some of the mutant LUSC genes were associated with the significantly altered tumoral expression of inhibitory immune checkpoint genes such asPD-L1,VISTA,TIM3andLAG3in human LUSCs. The novel findings of clonal evolution, mutational landscapes and expression signatures of LUSC suggested new targets for the overall LUSC therapy and the immunotherapy of LUSC.

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Methods Mentioned

BETA
exome-seq
scRNA-seq
exome-sequencing
exome sequencing
PCR
RNA-seq
chips
chip
Assay

Software Mentioned

BWA ( Burrows - Wheeler Aligner )
ComplexHeatmap
SciClone
R R Development Core Team
AltAnalyzer
ConsensusPathDB
Genome Analysis Toolkit ( GATK )
- TopHat
BWA
RSEM

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