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>  


==General==
==General==
===Genes===
Genes:<ref name=pmid27843590>{{cite journal |authors=Amatu A, Sartore-Bianchi A, Siena S |title=NTRK gene fusions as novel targets of cancer therapy across multiple tumour types |journal=ESMO Open |volume=1 |issue=2 |pages=e000023 |date=2016 |pmid=27843590 |pmc=5070277 |doi=10.1136/esmoopen-2015-000023 |url=https://www.ncbi.nlm.nih.gov/pubmed/27843590}}</ref>
*TRK1.
*NTRK1.
*TRK2.
*NTRK2.
*TRK3.
*NTRK3.


Notes:
Notes:
*The TRK genes are tropomyosine kinase receptors.
*The TRK genes are tropomyosine kinase receptors.
*Multiple fusion partners for each gene.
*Multiple fusion partners for each gene.
*Testing: RNA-based next generation sequencing or [[immunohistochemistry]] (limited sensitivity).<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>
 
Testing:  
*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.
*FISH breakapart probes.
*DNA NGS<ref>{{Cite journal  | last1 = Cocco | first1 = E. | last2 = Scaltriti | first2 = M. | last3 = Drilon | first3 = A. | title = NTRK fusion-positive cancers and TRK inhibitor therapy. | journal = Nat Rev Clin Oncol | volume = 15 | issue = 12 | pages = 731-747 | month = Dec | year = 2018 | doi = 10.1038/s41571-018-0113-0 | PMID = 30333516 }}
</ref> - sensitivity low for fusions.


==Associations==
==Associations==
===Classic===
===Classic===


*[[Mammary analogue secretory carcinoma]] (MASC) - ''ETV6-NTRK3.<ref name=pmid22127547>{{Cite journal  | last1 = Lei | first1 = Y. | last2 = Chiosea | first2 = SI. | title = Re-evaluating historic cohort of salivary acinic cell carcinoma with new diagnostic tools. | journal = Head Neck Pathol | volume = 6 | issue = 2 | pages = 166-70 | month = Jun | year = 2012 | doi = 10.1007/s12105-011-0312-9 | PMID = 22127547 }}</ref>
*[[Secretory carcinoma of the salivary gland]] (previously ''mammary analogue secretory carcinoma'') - ETV6-NTRK3.<ref name=pmid22127547>{{Cite journal  | last1 = Lei | first1 = Y. | last2 = Chiosea | first2 = SI. | title = Re-evaluating historic cohort of salivary acinic cell carcinoma with new diagnostic tools. | journal = Head Neck Pathol | volume = 6 | issue = 2 | pages = 166-70 | month = Jun | year = 2012 | doi = 10.1007/s12105-011-0312-9 | PMID = 22127547 }}</ref>
*[[Secretory breast carcinoma]] - ETV6-NTRK3.<ref name=pmid22129193>{{Cite journal  | last1 = Vasudev | first1 = P. | last2 = Onuma | first2 = K. | title = Secretory breast carcinoma: unique, triple-negative carcinoma with a favorable prognosis and characteristic molecular expression. | journal = Arch Pathol Lab Med | volume = 135 | issue = 12 | pages = 1606-10 | month = Dec | year = 2011 | doi = 10.5858/arpa.2010-0351-RS | PMID = 22129193 }}</ref>
*[[Secretory breast carcinoma]] - ETV6-NTRK3.<ref name=pmid22129193>{{Cite journal  | last1 = Vasudev | first1 = P. | last2 = Onuma | first2 = K. | title = Secretory breast carcinoma: unique, triple-negative carcinoma with a favorable prognosis and characteristic molecular expression. | journal = Arch Pathol Lab Med | volume = 135 | issue = 12 | pages = 1606-10 | month = Dec | year = 2011 | doi = 10.5858/arpa.2010-0351-RS | PMID = 22129193 }}</ref>
===Others===
===Others===
*[[Congenital-infantile fibrosarcoma]].<ref name=pmid11242790 >{{Cite journal  | last1 = Sheng | first1 = WQ. | last2 = Hisaoka | first2 = M. | last3 = Okamoto | first3 = S. | last4 = Tanaka | first4 = A. | last5 = Meis-Kindblom | first5 = JM. | last6 = Kindblom | first6 = LG. | last7 = Ishida | first7 = T. | last8 = Nojima | first8 = T. | last9 = Hashimoto | first9 = H. | title = Congenital-infantile fibrosarcoma. A clinicopathologic study of 10 cases and molecular detection of the ETV6-NTRK3 fusion transcripts using paraffin-embedded tissues. | journal = Am J Clin Pathol | volume = 115 | issue = 3 | pages = 348-55 | month = Mar | year = 2001 | doi = 10.1309/3H24-E7T7-V37G-AKKQ | PMID = 11242790 }}</ref>
*[[Congenital-infantile fibrosarcoma]].<ref name=pmid11242790 >{{Cite journal  | last1 = Sheng | first1 = WQ. | last2 = Hisaoka | first2 = M. | last3 = Okamoto | first3 = S. | last4 = Tanaka | first4 = A. | last5 = Meis-Kindblom | first5 = JM. | last6 = Kindblom | first6 = LG. | last7 = Ishida | first7 = T. | last8 = Nojima | first8 = T. | last9 = Hashimoto | first9 = H. | title = Congenital-infantile fibrosarcoma. A clinicopathologic study of 10 cases and molecular detection of the ETV6-NTRK3 fusion transcripts using paraffin-embedded tissues. | journal = Am J Clin Pathol | volume = 115 | issue = 3 | pages = 348-55 | month = Mar | year = 2001 | doi = 10.1309/3H24-E7T7-V37G-AKKQ | PMID = 11242790 }}</ref>
*[[Mesoblastic nephroma]].<ref name=pmid29893456>{{Cite journal  | last1 = Halalsheh | first1 = H. | last2 = McCarville | first2 = MB. | last3 = Neel | first3 = M. | last4 = Reynolds | first4 = M. | last5 = Cox | first5 = MC. | last6 = Pappo | first6 = AS. | title = Dramatic bone remodeling following larotrectinib administration for bone metastasis in a patient with TRK fusion congenital mesoblastic nephroma. | journal = Pediatr Blood Cancer | volume = 65 | issue = 10 | pages = e27271 | month = Oct | year = 2018 | doi = 10.1002/pbc.27271 | PMID = 29893456 }}</ref>
*Cellular [[mesoblastic nephroma]].<ref name=pmid29893456>{{Cite journal  | last1 = Halalsheh | first1 = H. | last2 = McCarville | first2 = MB. | last3 = Neel | first3 = M. | last4 = Reynolds | first4 = M. | last5 = Cox | first5 = MC. | last6 = Pappo | first6 = AS. | title = Dramatic bone remodeling following larotrectinib administration for bone metastasis in a patient with TRK fusion congenital mesoblastic nephroma. | journal = Pediatr Blood Cancer | volume = 65 | issue = 10 | pages = e27271 | month = Oct | year = 2018 | doi = 10.1002/pbc.27271 | PMID = 29893456 }}</ref><ref name=pmid29683818>{{Cite journal  | last1 = Rudzinski | first1 = ER. | last2 = Lockwood | first2 = CM. | last3 = Stohr | first3 = BA. | last4 = Vargas | first4 = SO. | last5 = Sheridan | first5 = R. | last6 = Black | first6 = JO. | last7 = Rajaram | first7 = V. | last8 = Laetsch | first8 = TW. | last9 = Davis | first9 = JL. | title = Pan-Trk Immunohistochemistry Identifies NTRK Rearrangements in Pediatric Mesenchymal Tumors. | journal = Am J Surg Pathol | volume = 42 | issue = 7 | pages = 927-935 | month = Jul | year = 2018 | doi = 10.1097/PAS.0000000000001062 | PMID = 29683818 }}</ref>
*NTRK1 fusions occasionally in [[Glioblastoma]] (1-2%).<ref>{{Cite journal  | last1 = Xu | first1 = T. | last2 = Wang | first2 = H. | last3 = Huang | first3 = X. | last4 = Li | first4 = W. | last5 = Huang | first5 = Q. | last6 = Yan | first6 = Y. | last7 = Chen | first7 = J. | title = Gene Fusion in Malignant Glioma: An Emerging Target for Next-Generation Personalized Treatment. | journal = Transl Oncol | volume = 11 | issue = 3 | pages = 609-618 | month = Jun | year = 2018 | doi = 10.1016/j.tranon.2018.02.020 | PMID = 29571074 }}</ref>
*SQSTM1-NTRK1 non-small cell carcinoma (~0.1%).<ref>{{Cite journal  | last1 = Agaimy | first1 = A. | last2 = Hartmann | first2 = A. | last3 = Antonescu | first3 = CR. | last4 = Chiosea | first4 = SI. | last5 = El-Mofty | first5 = SK. | last6 = Geddert | first6 = H. | last7 = Iro | first7 = H. | last8 = Lewis | first8 = JS. | last9 = Märkl | first9 = B. | title = SMARCB1 (INI-1)-deficient Sinonasal Carcinoma: A Series of 39 Cases Expanding the Morphologic and Clinicopathologic Spectrum of a Recently Described Entity. | journal = Am J Surg Pathol | volume = 41 | issue = 4 | pages = 458-471 | month = Apr | year = 2017 | doi = 10.1097/PAS.0000000000000797 | PMID = 28291122 }}</ref>


==Drugs==
==Drugs==
*Merestinib.
*Merestinib.
*Larotrectinib.<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>
*Larotrectinib.<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>
*Entrectinib.<ref name=pmid26565381>{{Cite journal  | last1 = Farago | first1 = AF. | last2 = Le | first2 = LP. | last3 = Zheng | first3 = Z. | last4 = Muzikansky | first4 = A. | last5 = Drilon | first5 = A. | last6 = Patel | first6 = M. | last7 = Bauer | first7 = TM. | last8 = Liu | first8 = SV. | last9 = Ou | first9 = SH. | title = Durable Clinical Response to Entrectinib in NTRK1-Rearranged Non-Small Cell Lung Cancer. | journal = J Thorac Oncol | volume = 10 | issue = 12 | pages = 1670-4 | month = Dec | year = 2015 | doi = 10.1097/01.JTO.0000473485.38553.f0 | PMID = 26565381 }}</ref>
*Others.
*Others.


Latest revision as of 20:04, 18 October 2023

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.[1]

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.
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