RET gene alterations occur in various
tumour types and are a therapeutic target
in thyroid cancer and NSCLC.1,2,8,9
The prevalence of oncogenic RET gene alterations (fusions or mutations) varies according to the tumour type.1–7
RET mutations are seen in approximately 70% of medullary thyroid cancers (MTC), including up to 95% of patients with familial MTC and >65% of patients with sporadic MTC.6,7
RET fusions are seen in 10–20% of papillary thyroid cancer (PTC) and other thyroid cancers. They are also found in 1–2% of NSCLC and in a variety of solid tumour at lower frequencies.1-9
Testing for RET brings the positives of precision therapy to patients with RET-altered cancers
ESMO recommends routine molecular testing for RET alterations in medullary thyroid cancer (MTC) and in non- MTC, NSCLC and other solid tumours by NGS or PCR.1,2
Testing for RET+ rearrangement should be systematically carried out in advanced NSCLC10
NGS is increasingly being used and is a sensitive and accurate test to identify most RET gene fusions with a single test9,13–19
FISH has been the standard approach to detecting RET gene rearrangements10
RT-PCR has good sensitivity and specificity; however, its use may be limited by the presence of numerous RET fusion partners, both identified and still unknown, and difficulties in obtaining good-quality RNA12
The RET protein plays an important role in healthy tissue and if altered by fusion events or mutations drives cancer through aberrant signalling27
CNS, central nervous system; FISH, fluorescence in situ hybridisation; IHC, immunohistochemistry; NGS, next-generation sequencing; NSCLC, non-small cell lung cancer; RT-PCR, reverse transcription polymerase chain reaction.
1. Bergethon K, et al. J Clin Oncol 2012;30:863–870.
2. Dugay F, et al. Oncotarget 2017;8:53336–53351.
3. Patil T, et al. J Thorac Oncol 2018;13:1717–1726.
4. Gainor JF, et al. JCO Precis Oncol 2017. DOI: 10.1200/PO.17.00063.
5. Qiu Z et al. Sci Rep 2020;10:10387;
6. Gainor JF, Shaw AT. Oncologist 2013;18:865–875;
7. Genentech USA, Inc. ALECENSA Prescribing Information. 2021;
8. Oikawa A, et al. Oncol Lett 2012;3:629–634.
9. Bubendorf L, et al. Virchows Arch 2016;469:489–503.
10. Planchard D. Ann Oncol 2018;29:iv192–iv237.
11. International Association for the Study of Lung Cancer. IASLC Atlas of ALK and ROS1 testing in lung cancer. Available at: https://www.iaslc.org/research-education/publications-resources-guidelines/iaslc-atlas-alk-and-ros1-testing-lung-cancer (Accessed November 2020).
12. Rossi G, et al. Lung Cancer (Auckl) 2017:8:45–55.
13. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Non-Small Cell Lung Cancer. V.6.2020, 2020. Available at: https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf (Accessed November 2020).
14. Diaz L, Bardelli A. J Clin Oncol 2014;32:579–586.
15. Shan L, et al. PLoS One 2015;10:e0120422.
16. Cao B, et al. Onco Targets Ther 2016;31:131–138.
17. Zheng Z, et al. Nat Med 2014;20:1479–1484.
18. Drilon A, et al. Clin Cancer Res 2015;21:3631–3639.
19. Grada A, Weinbrecht K. J Invest Dermatol 2013;133:e11.
20. Birchmeier C, et al. Proc Natl Acad Sci U S A 1987;84: 9270–9274.
21. Rikova K, et al. Cell 2007;131:1190–1203.
22. Gainor J, Shaw A. Oncologist 2013;18:865–875.
27. Thein et al; 2021; Trends in Cancer 2021; 7 1074-1088
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