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Review

NTRK Fusions in Central Nervous System Tumors: A Rare, but Worthy Target

by
Alessandro Gambella
1,
Rebecca Senetta
2,
Giammarco Collemi
1,
Stefano Gabriele Vallero
3,
Matteo Monticelli
4,
Fabio Cofano
4,
Pietro Zeppa
4,
Diego Garbossa
4,
Alessia Pellerino
5,
Roberta Rudà
5,
Riccardo Soffietti
5,
Franca Fagioli
3,
Mauro Papotti
2,
Paola Cassoni
1 and
Luca Bertero
1,*
1
Pathology Unit, Department of Medical Sciences, University of Turin, 10126 Turin, Italy
2
Pathology Unit, Department of Oncology, University of Turin, 10126 Turin, Italy
3
Pediatric Onco-Hematology Unit, Department of Pediatric and Public Health Sciences, University of Turin, 10126 Turin, Italy
4
Neurosurgery Unit, Department of Neurosciences, University of Turin, 10126 Turin, Italy
5
Department of Neuro-Oncology, University and City of Health and Science Hospital, 10126 Turin, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(3), 753; https://doi.org/10.3390/ijms21030753
Submission received: 30 December 2019 / Revised: 20 January 2020 / Accepted: 21 January 2020 / Published: 23 January 2020
(This article belongs to the Special Issue Molecular Biology of Brain Tumors)
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Abstract

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.
Keywords: central nervous system; glioma; pediatric tumors; molecular pathology; NTRK; gene fusion; targeted therapies; precision medicine central nervous system; glioma; pediatric tumors; molecular pathology; NTRK; gene fusion; targeted therapies; precision medicine

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MDPI and ACS Style

Gambella, A.; Senetta, R.; Collemi, G.; Vallero, S.G.; Monticelli, M.; Cofano, F.; Zeppa, P.; Garbossa, D.; Pellerino, A.; Rudà, R.; et al. NTRK Fusions in Central Nervous System Tumors: A Rare, but Worthy Target. Int. J. Mol. Sci. 2020, 21, 753. https://doi.org/10.3390/ijms21030753

AMA Style

Gambella A, Senetta R, Collemi G, Vallero SG, Monticelli M, Cofano F, Zeppa P, Garbossa D, Pellerino A, Rudà R, et al. NTRK Fusions in Central Nervous System Tumors: A Rare, but Worthy Target. International Journal of Molecular Sciences. 2020; 21(3):753. https://doi.org/10.3390/ijms21030753

Chicago/Turabian Style

Gambella, Alessandro, Rebecca Senetta, Giammarco Collemi, Stefano Gabriele Vallero, Matteo Monticelli, Fabio Cofano, Pietro Zeppa, Diego Garbossa, Alessia Pellerino, Roberta Rudà, and et al. 2020. "NTRK Fusions in Central Nervous System Tumors: A Rare, but Worthy Target" International Journal of Molecular Sciences 21, no. 3: 753. https://doi.org/10.3390/ijms21030753

APA Style

Gambella, A., Senetta, R., Collemi, G., Vallero, S. G., Monticelli, M., Cofano, F., Zeppa, P., Garbossa, D., Pellerino, A., Rudà, R., Soffietti, R., Fagioli, F., Papotti, M., Cassoni, P., & Bertero, L. (2020). NTRK Fusions in Central Nervous System Tumors: A Rare, but Worthy Target. International Journal of Molecular Sciences, 21(3), 753. https://doi.org/10.3390/ijms21030753

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