Gene fusion

Gene fusion is a common event in cancer and a re-occuring theme in molecular pathology. It is hybrid of two coding or regulatory DNA sequences.

General

Caused by genomic rearrangements such as:

• translocation.
• deletion.
• duplication.
• inversion.

First fusion was described as BCR-ABL1 fusion in CML. Subsequently Imatinib was the first inhibitor targeting CML with BCR-ABL1 fusion.

Methodology

Gene fusions can be detected by:

• RT-PCR (fusion partners need to be known).
• FISH.
• RNA-Sequencing.
• Whole Genome sequencing (WGS) (Comprehensive and unbiased, but short read length).
• Immunohistochemistry (not suitable/available for all fusions).

Examples

Common fusion in Neuropathology:

• KIAA1549-BRAF fusion in pilocytic astrocytoma (up to 70%).
• NAB2-STAT6 fusion in Solitary fibrous tumour.
• RELA fusion in supratentorial ependymoma (up to 70% in children).