Pan-cancer transcriptomic analysis associates long non-coding RNAs with key mutational driver events

Area of Science:

• Genomics
• Cancer Biology
• Transcriptomics

Background:

• Long non-coding RNAs (lncRNAs) are increasingly recognized for their roles in cancer.
• Understanding how lncRNA expression is affected by somatic mutations is crucial for cancer research.

Purpose of the Study:

• To identify lncRNAs that are transcriptionally altered in response to key oncogenic driver mutations across diverse human cancers.
• To associate novel lncRNAs with specific oncogenic pathways and regulatory networks.

Main Methods:

• Analysis of transcriptome and exome sequencing data from thousands of tumors across 19 cancer types.
• Identification of lncRNAs induced or repressed in relation to somatic mutations in driver genes.
• Assessment of reproducibility and co-expression patterns with neighboring genes.

Main Results:

• A comprehensive catalog of lncRNAs associated with somatic mutations in oncogenic pathways was generated.
• Known and numerous novel lncRNAs were linked to cancer-driving mutations, often reproducibly across cancer types.
• Specific lncRNAs were highlighted for their potential roles downstream of TP53 and NFE2L2.

Conclusions:

• Somatic mutations in key driver genes significantly impact lncRNA expression profiles in human cancers.
• This study provides a valuable resource for understanding lncRNA functions in cancer pathogenesis and identifies potential therapeutic targets.