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A gene fusion is two genes broken and joined together, creating a hybrid protein that can drive cancer. Fusion-driven cancers are often exquisitely drug-sensitive.
A gene fusion joins two broken genes into one, producing a hybrid protein that can drive cancer, and fusion-driven cancers are often exquisitely drug-sensitive. Well-known examples include EML4-ALK, ROS1, RET, NTRK, FGFR2, NRG1 and BCR-ABL, and the ALK, RET, NTRK and FGFR2 targets are linked here. Fusions are best detected by RNA sequencing & expression profiling, define tumour-agnostic indications for NTRK and RET, and are the archetype of oncogene addiction. The term is cited by the Biliary tract cancer and Ewing sarcoma entries, by FGFR2 fusions and rearrangements, by Janet Rowley, Arul M. Chinnaiyan and Olivier Delattre, and by ideas on degraders for the fusion proteins that drive childhood sarcomas and a standard for tumour-agnostic approvals.
In plain words · ALK is a gene fusion driver in about 4 to 5% of non-small-cell lung cancers that responds to a succession of ALK inhibitor pills. Lorlatinib kept about 60% of patients progression-free at five years, alectinib is approved after surgery, and neladalkib targets compound resistance mutations.
Showing the target this term concerns: ALK.
The glossary entry explains the word; the readout page carries the scoring rule, the thresholds approvals use, the companion diagnostics and the tests.
The current first choice for ALK-positive lung cancer in most guidelines, and the strongest evidence in solid tumour oncology that a drug can be designed to work inside the brain. Five-year follow-up has since shown the majority of patients still progression-free.
It turned the laboratory prediction into a clinical rule: after a second-generation ALK inhibitor, genotype the tumour, and treat the absence of an ALK mutation as evidence that the cancer has stopped depending on ALK.
It put a number on how rare NRG1 fusions are and showed that heterogeneous partners make RNA-based testing the only reliable way to find them, which is the practical argument for adding a fusion panel to a driver-negative lung cancer work-up.
It is the quantitative answer to why prostate cancer has so few targeted therapies. The common events are not druggable, the druggable ones are individually rare, and no trial can be powered on a driver present in 2% of men without an international basket.
It is the document that defines what a complete lung cancer molecular report looks like, and its asymmetry about plasma, rule in but never rule out, is the single most useful sentence in it.
It is the reason a prostate cancer fusion frequency quoted without an ancestry is unsafe. In this cohort the founder event that defines almost half of Western tumours is uncommon, and the fusion-negative, CHD1-deleted route dominates instead.
It made repeat biopsy and genotyping at progression the standard in ALK-positive lung cancer, because after a second-generation inhibitor the presence or absence of an ALK mutation is what separates patients who should receive a third-generation inhibitor from those who should not.
The paper that separated the biliary tree into molecular subtypes: FGFR2 and IDH belong to the intrahepatic ducts, while gallbladder cancer carries HER2, ELF3 and an APOBEC signature. Its hypermutated, checkpoint-high poor-prognosis group foreshadowed immunotherapy.
Shares Detection of NRG1 gene fusions in solid tumors, A standard for tumour-agnostic approvals: minimum histologies and hierarchical modelling, Develop drugs in children first when the target is a children's target, RET fusion and RET mutation.
Shares The TMPRSS2-ERG rearrangement, ERG expression and prostate cancer outcomes: a cohort study and meta-analysis, Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer, Whole-genome and transcriptome sequencing of prostate cancer identifies new genetic alterations driving disease progression, The long tail of oncogenic drivers in prostate cancer.
Shares The TMPRSS2-ERG rearrangement, ERG expression and prostate cancer outcomes: a cohort study and meta-analysis, Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer, Whole-genome and transcriptome sequencing of prostate cancer identifies new genetic alterations driving disease progression, SPOP mutation.
Shares PROFILE 1001 ROS1 expansion cohort, University of Colorado Cancer Center, PROFILE 1014, Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer.
Shares PROFILE 1001 ROS1 expansion cohort, ROS1 fusion (ROS1-positive), NTRK1/2/3 gene fusion, Inflammatory myofibroblastic tumour (IMT).
Shares NRG1, ALK fusion (ALK-positive), NTRK1/2/3 gene fusion, NTRK.
Shares PROFILE 1001 ROS1 expansion cohort, ROS1 fusion (ROS1-positive), Philadelphia chromosome (Ph+, BCR::ABL1), RET fusion and RET mutation.
Shares The TMPRSS2-ERG rearrangement, ERG expression and prostate cancer outcomes: a cohort study and meta-analysis, Whole-genome and transcriptome sequencing of prostate cancer identifies new genetic alterations driving disease progression, TMPRSS2-ERG fusion (and the other ETS rearrangements), Integrative genomic profiling of human prostate cancer.