Gene fusions in gastrointestinal tract cancers

Abstract

Fusion genes have been identified in a wide array of human neoplasms including hematologic and solid tumors, including gastrointestinal tract neoplasia. A fusion gene is the product of parts of two genes that are joined together following a deletion, translocation, or chromosomal inversion. Together with single nucleotide variants, insertions, deletions, and amplification, fusion genes represent one of the key genomic mechanisms for tumor development. Detecting fusions in the clinic is accomplished by a variety of techniques including break‐apart fluorescence in situ hybridization, reverse transcription‐polymerase chain reaction, and next‐generation sequencing. Some recurrent gene fusions have been successfully targeted by small molecule or monoclonal antibody therapies (ie targeted therapies), while others are used as biomarkers for diagnostic and prognostic purposes. The purpose of this review article is to discuss the clinical utility of detection of gene fusions in carcinomas and neoplasms arising primarily in the digestive system.

Creative destruction: New protein folds from old

“…Creative destruction is not limited to the genesis of new folds at the dawn of life but appears to be ongoing today. In many cancers for example, chromosomal translocations commonly cause gene fusion ( 74 – 76 ). Breakpoint cluster region-Abelson murine leukemia (BCR-ABL) ( 77 , 78 ) and Echinoderm microtubule associated protein like 4-Anaplastic lymphoma kinase (EML4-ALK) ( 79 ) are transforming genes that produce fused proteins.…”

Advancing nanotechnology for neoantigen-based cancer theranostics

“…Gene fusions are commonly found in various types of human neoplasms, occurring with differing frequencies in both hematologic and solid tumours. [43][44][45][46] These gene fusions emerge when segments of two genes become linked together due to DNA rearrangements caused by processes like deletions, translocations, or chromosomal inversions. This process has the potential to generate fused immunogenic neoantigens.…”

“…This process has the potential to generate fused immunogenic neoantigens. 36,43,47 For example, Weber and his research team conducted a study to assess the prevalence and association of gene fusions (GFs) as a novel category of epitopes. 46 They utilized the EasyFuse tool to predict the presence of GFs in a substantial collection of 57 freshly frozen breast cancer specimens.…”