RET | abbreviation : rearranged during transfection : one of several mutations currently identified as the driver, or underlying cause, of lung cancer.
RET-positive cancer is a type of cancer caused by a mutation or abnormal re-arrangement of the RET gene, which codes for a cell membrane receptor and member of the tyrosine protein kinase family of proteins. This leads to abnormal activation of the cell membrane receptor, basically resulting in the “on-off” switch to get stuck in the “on” position and causing these abnormal cells to multiply and spread – thereby “driving” the cancer growth. Testing the cancer by sending a tissue sample from a tumor, or by sending a blood sample for a circulating ‘cell free DNA’ (cf DNA) blood test to a laboratory, to check for specific genetic changes is the only way to detect cancer drivers like RET. If the test result is positive for a RET mutation or abnormal rearrangement of the RET gene, this information can help to identify treatment and clinical research options. RET driver mutations occur most commonly in Lung cancer and in several types of inherited and sporadic thyroid cancers, but RET gene mutations can also be seen in small numbers of patients with paraganglioma, ovarian and breast, pancreatic, bladder and colorectal cancers, among others.(1,2)
Abnormal re-arrangement or abnormal fusion of the RET gene occurs in 1-2% of all lung adenocarcinomas (also called Non-small cell lung cancer, or NSCLC). Although this is a small percentage of overall lung cancer cases, given that lung cancer is the number one cause of cancer related deaths and that around 1.8 million new lung cancer cases are reported annually worldwide, the number of new RET positive lung cancer patients diagnosed each year is still considerable – about 20,000-30,000 people yearly.
Overall, NSCLC is more common among women, and RET fusions associated with NSCLC are more prevalent in younger patients who have never or rarely smoked.(3) The most frequent abnormal RET fusion partner genes in NSCLC are RET-KIF5B followed by RET-CCDC6, though at least 30 fusion partner genes have been identified to date(4). The significance of these fusion variants in terms of overall prognosis remains unclear.
©LUNGevity Foundation video below. Used with permission.
Those more likely to have RET positive lung cancer are:
Women more commonly than men
NSCLC or lung adenocarcinoma is more common in women overall, and RET fusions associated with NSCLC are more prevalent in younger patients who have never or rarely smoked. Abnormal fusion of the RET gene occurs in 1-2% of all lung adenocarcinomas, which is about 30,000 people annually.
- Kato S, Subbiah V, Marchlik E, Elkin SK, Carter JL, Kurzrock R. RET aberrations in diverse cancers: next-generation sequencing of 4,871 patients. Clin Cancer Res. 2017;23(8):1988-1997. doi:10.1158/1078-0432.CCR-16-1679
- Li AY, McCusker MG, Russo A, et al. RET fusions in solid tumors. Cancer Treat Rev. 2019;81:101911. doi:10.1016/j.ctrv.2019.101911
- Subbiah V, Yang D, Velcheti V, Drilon A, Meric-Bernstam F. State-of-the-art strategies for targeting RET-dependent cancers. J Clin Oncol. 2020;38(11):1209-1221. doi:10.1200/JCO.19.02551
- Mulligan LM. GDNF and the RET receptor in cancer: new insights and therapeutic potential. Front Physiol. 2019;9:1873. doi:10.3389/fphys.2018.01873
The above information was obtained with permission from RETpositive.org