Transcriptome sequencing to detect gene fusions in cancer

Area of Science:

• Genomics
• Cancer Biology
• Bioinformatics

Background:

• Recurrent gene fusions are hallmarks of hematological malignancies and rare tumors.
• Recent findings indicate their presence in common solid tumors, necessitating new discovery methods.

Purpose of the Study:

• To establish a robust pipeline for discovering novel gene fusions using integrative transcriptome sequencing.
• To validate the pipeline by re-discovering known fusions and identifying novel ones.

Main Methods:

• Integrative analysis of high-throughput long- and short-read transcriptome sequencing data.
• Bioinformatic pipeline for identifying chimaeric transcripts.
• Experimental validation of novel gene fusions.

Main Results:

• Successfully re-discovered BCR-ABL1 and TMPRSS2-ERG gene fusions.
• Nominated and experimentally validated novel gene fusions in cancer cell lines and tumors.
• Demonstrated the utility of the pipeline for comprehensive characterization of gene fusions.

Conclusions:

• The developed pipeline offers a robust approach for discovering novel gene fusions in cancer.
• This work expands the understanding of gene fusions in common solid tumors.
• Facilitates comprehensive characterization of cancer-associated gene chimeras.