Difference between revisions of "TRK fusions"

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[[Image: Mammary analogue secretory carcinoma (H&E, medium power).jpg | thumb | [[Secretory carcinoma of the salivary gland]] is a tumour that is characterized by TRK fusions. [[H&E stain]]. (WC/NormanDy)]]
'''TRK fusions''' are seen in many solid tumours of children and adults and have targeted drugs.<ref name=pmid29466156>{{Cite journal  | last1 = Drilon | first1 = A. | last2 = Laetsch | first2 = TW. | last3 = Kummar | first3 = S. | last4 = DuBois | first4 = SG. | last5 = Lassen | first5 = UN. | last6 = Demetri | first6 = GD. | last7 = Nathenson | first7 = M. | last8 = Doebele | first8 = RC. | last9 = Farago | first9 = AF. | title = Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children. | journal = N Engl J Med | volume = 378 | issue = 8 | pages = 731-739 | month = 02 | year = 2018 | doi = 10.1056/NEJMoa1714448 | PMID = 29466156 }}</ref>  
'''TRK fusions''' are seen in many solid tumours of children and adults and have targeted drugs.<ref name=pmid29466156>{{Cite journal  | last1 = Drilon | first1 = A. | last2 = Laetsch | first2 = TW. | last3 = Kummar | first3 = S. | last4 = DuBois | first4 = SG. | last5 = Lassen | first5 = UN. | last6 = Demetri | first6 = GD. | last7 = Nathenson | first7 = M. | last8 = Doebele | first8 = RC. | last9 = Farago | first9 = AF. | title = Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children. | journal = N Engl J Med | volume = 378 | issue = 8 | pages = 731-739 | month = 02 | year = 2018 | doi = 10.1056/NEJMoa1714448 | PMID = 29466156 }}</ref>  


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Testing:  
Testing:  
*RNA-based next generation sequencing.
*RNA-based [[next generation sequencing]].
*[[Immunohistochemistry]]<ref name=pmid28719467>{{Cite journal  | last1 = Hechtman | first1 = JF. | last2 = Benayed | first2 = R. | last3 = Hyman | first3 = DM. | last4 = Drilon | first4 = A. | last5 = Zehir | first5 = A. | last6 = Frosina | first6 = D. | last7 = Arcila | first7 = ME. | last8 = Dogan | first8 = S. | last9 = Klimstra | first9 = DS. | title = Pan-Trk Immunohistochemistry Is an Efficient and Reliable Screen for the Detection of NTRK Fusions. | journal = Am J Surg Pathol | volume = 41 | issue = 11 | pages = 1547-1551 | month = Nov | year = 2017 | doi = 10.1097/PAS.0000000000000911 | PMID = 28719467 }}</ref> - limited sensitivity for leiomyosarcoma, neural differentiation tumours.
*[[Immunohistochemistry]]<ref name=pmid28719467>{{Cite journal  | last1 = Hechtman | first1 = JF. | last2 = Benayed | first2 = R. | last3 = Hyman | first3 = DM. | last4 = Drilon | first4 = A. | last5 = Zehir | first5 = A. | last6 = Frosina | first6 = D. | last7 = Arcila | first7 = ME. | last8 = Dogan | first8 = S. | last9 = Klimstra | first9 = DS. | title = Pan-Trk Immunohistochemistry Is an Efficient and Reliable Screen for the Detection of NTRK Fusions. | journal = Am J Surg Pathol | volume = 41 | issue = 11 | pages = 1547-1551 | month = Nov | year = 2017 | doi = 10.1097/PAS.0000000000000911 | PMID = 28719467 }}</ref> - limited sensitivity for leiomyosarcoma, neural differentiation tumours.
*FISH breakapart probes.
*FISH breakapart probes.

Latest revision as of 20:04, 18 October 2023

TRK fusions are seen in many solid tumours of children and adults and have targeted drugs.[1]

Secretory carcinoma of the salivary gland is a tumour that is characterized by TRK fusions. H&E stain. (WC/NormanDy)

General

Genes:[2]

  • NTRK1.
  • NTRK2.
  • NTRK3.

Notes:

  • The TRK genes are tropomyosine kinase receptors.
  • Multiple fusion partners for each gene.

Testing:

Associations

Classic

Others

Drugs

  • Merestinib.
  • Larotrectinib.[1]
  • Entrectinib.[12]
  • Others.

See also

References

  1. 1.0 1.1 Drilon, A.; Laetsch, TW.; Kummar, S.; DuBois, SG.; Lassen, UN.; Demetri, GD.; Nathenson, M.; Doebele, RC. et al. (02 2018). "Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children.". N Engl J Med 378 (8): 731-739. doi:10.1056/NEJMoa1714448. PMID 29466156.
  2. Amatu A, Sartore-Bianchi A, Siena S (2016). "NTRK gene fusions as novel targets of cancer therapy across multiple tumour types". ESMO Open 1 (2): e000023. doi:10.1136/esmoopen-2015-000023. PMC 5070277. PMID 27843590. https://www.ncbi.nlm.nih.gov/pubmed/27843590.
  3. Hechtman, JF.; Benayed, R.; Hyman, DM.; Drilon, A.; Zehir, A.; Frosina, D.; Arcila, ME.; Dogan, S. et al. (Nov 2017). "Pan-Trk Immunohistochemistry Is an Efficient and Reliable Screen for the Detection of NTRK Fusions.". Am J Surg Pathol 41 (11): 1547-1551. doi:10.1097/PAS.0000000000000911. PMID 28719467.
  4. Cocco, E.; Scaltriti, M.; Drilon, A. (Dec 2018). "NTRK fusion-positive cancers and TRK inhibitor therapy.". Nat Rev Clin Oncol 15 (12): 731-747. doi:10.1038/s41571-018-0113-0. PMID 30333516.
  5. Lei, Y.; Chiosea, SI. (Jun 2012). "Re-evaluating historic cohort of salivary acinic cell carcinoma with new diagnostic tools.". Head Neck Pathol 6 (2): 166-70. doi:10.1007/s12105-011-0312-9. PMID 22127547.
  6. Vasudev, P.; Onuma, K. (Dec 2011). "Secretory breast carcinoma: unique, triple-negative carcinoma with a favorable prognosis and characteristic molecular expression.". Arch Pathol Lab Med 135 (12): 1606-10. doi:10.5858/arpa.2010-0351-RS. PMID 22129193.
  7. Sheng, WQ.; Hisaoka, M.; Okamoto, S.; Tanaka, A.; Meis-Kindblom, JM.; Kindblom, LG.; Ishida, T.; Nojima, T. et al. (Mar 2001). "Congenital-infantile fibrosarcoma. A clinicopathologic study of 10 cases and molecular detection of the ETV6-NTRK3 fusion transcripts using paraffin-embedded tissues.". Am J Clin Pathol 115 (3): 348-55. doi:10.1309/3H24-E7T7-V37G-AKKQ. PMID 11242790.
  8. Halalsheh, H.; McCarville, MB.; Neel, M.; Reynolds, M.; Cox, MC.; Pappo, AS. (Oct 2018). "Dramatic bone remodeling following larotrectinib administration for bone metastasis in a patient with TRK fusion congenital mesoblastic nephroma.". Pediatr Blood Cancer 65 (10): e27271. doi:10.1002/pbc.27271. PMID 29893456.
  9. Rudzinski, ER.; Lockwood, CM.; Stohr, BA.; Vargas, SO.; Sheridan, R.; Black, JO.; Rajaram, V.; Laetsch, TW. et al. (Jul 2018). "Pan-Trk Immunohistochemistry Identifies NTRK Rearrangements in Pediatric Mesenchymal Tumors.". Am J Surg Pathol 42 (7): 927-935. doi:10.1097/PAS.0000000000001062. PMID 29683818.
  10. Xu, T.; Wang, H.; Huang, X.; Li, W.; Huang, Q.; Yan, Y.; Chen, J. (Jun 2018). "Gene Fusion in Malignant Glioma: An Emerging Target for Next-Generation Personalized Treatment.". Transl Oncol 11 (3): 609-618. doi:10.1016/j.tranon.2018.02.020. PMID 29571074.
  11. Agaimy, A.; Hartmann, A.; Antonescu, CR.; Chiosea, SI.; El-Mofty, SK.; Geddert, H.; Iro, H.; Lewis, JS. et al. (Apr 2017). "SMARCB1 (INI-1)-deficient Sinonasal Carcinoma: A Series of 39 Cases Expanding the Morphologic and Clinicopathologic Spectrum of a Recently Described Entity.". Am J Surg Pathol 41 (4): 458-471. doi:10.1097/PAS.0000000000000797. PMID 28291122.
  12. Farago, AF.; Le, LP.; Zheng, Z.; Muzikansky, A.; Drilon, A.; Patel, M.; Bauer, TM.; Liu, SV. et al. (Dec 2015). "Durable Clinical Response to Entrectinib in NTRK1-Rearranged Non-Small Cell Lung Cancer.". J Thorac Oncol 10 (12): 1670-4. doi:10.1097/01.JTO.0000473485.38553.f0. PMID 26565381.