NTRK Fusions in Central Nervous System Tumors: A Rare, but Worthy Target.
The neurotrophic tropomyosin receptor kinase (NTRK) genes (NTRK1, NTRK2, and NTRK3) code for three transmembrane high-affinity tyrosine-kinase receptors for nerve growth factors (TRK-A, TRK-B, and TRK-C) which are mainly involved in nervous system development. Loss of function alterations in these genes can lead to nervous system development problems; conversely, activating alterations harbor oncogenic potential, promoting cell proliferation/survival and tumorigenesis. Chromosomal rearrangements are the most clinically relevant alterations of pathological NTRK activation, leading to constitutionally active chimeric receptors. NTRK fusions have been detected with extremely variable frequencies in many pediatric and adult cancer types, including central nervous system (CNS) tumors. These alterations can be detected by different laboratory assays (e.g., immunohistochemistry, FISH, sequencing), but each of these approaches has specific advantages and limitations which must be taken into account for an appropriate use in diagnostics or research. Moreover, therapeutic targeting of this molecular marker recently showed extreme efficacy. Considering the overall lack of effective treatments for brain neoplasms, it is expected that detection of NTRK fusions will soon become a mainstay in the diagnostic assessment of CNS tumors, and thus in-depth knowledge regarding this topic is warranted.
['Gambella|Alessandro|A|', 'Senetta|Rebecca|R|', 'Collemi|Giammarco|G|', 'Vallero|Stefano Gabriele|SG|', 'Monticelli|Matteo|M|', 'Cofano|Fabio|F|', 'Zeppa|Pietro|P|', 'Garbossa|Diego|D|', 'Pellerino|Alessia|A|', 'Rudà|Roberta|R|', 'Soffietti|Riccardo|R|', 'Fagioli|Franca|F|', 'Papotti|Mauro|M|', 'Cassoni|Paola|P|', 'Bertero|Luca|L|']
D000818:Animals D014408:Biomarkers, Tumor D016543:Central Nervous System Neoplasms D050939:Gene Fusion D006801:Humans D008562:Membrane Glycoproteins D057285:Precision Medicine D047428:Protein Kinase Inhibitors D020917:Receptor, trkA D020813:Receptor, trkB D020812:Receptor, trkC D015398:Signal Transduction
NTRK central nervous system gene fusion glioma molecular pathology pediatric tumors precision medicine targeted therapies