Allele-specific expression in non-small cell lung cancer: A genome-wide investigation

Several studies have suggested that allele-specific expression (ASE)plays a critical role in cancer initiation and progression. However, little is known about genome-wide ASE and monoallelic expression of genes in non-small cell lung cancer (NSCLC). We analysed 11,422 genes that had either at least two Single Nucleotide Variations (SNVs) or a high-confidence single SNV (depth ≥10) in metastatic NSCLC samples, and found that approximately 43 % (4935 genes) exhibited monoallelic expression in at least one sample. On average 21% of genes in each sample showed monoallelic expression. These genes were involved in key cancer hallmarks, including tumour growth, metastasis, maintenance of tumour microenvironment, and cell proliferation. Several important NSCLC driver genes, such as CDH1, STK11, MYH9, ZNF395, TP53, EGFR, JAK2, RB1, CREBBP, FAT4, APC, CTNNB1, and TFRC, were identified in our monoallelically expressed (MAE) gene panel. This suggests that monoallelic expression plays a significant role in how these genes influence NSCLC growth and progression. In addition to the driver genes, the monoallelically expressed gene panel was enriched with imprinted genes. Of the 4935 unique MAE genes 52 genes were either known imprinted or predicted to be imprinted. Interestingly, individual-specific monoallelic expression of genes was predominantly observed, although, 134 genes exhibited consistent monoallelic expression across the samples, indicating that a significant proportion of MAE genes are individual-specific. These consistent MAE genes were found to interact with both MAE and non-MAE genes, highlighting a well-connected network of MAE genes. Overall, these findings could contribute to the development of effective diagnostic and prognostic models and support efforts in implementing tailored treatment strategies and vaccines for NSCLC.