LUNG CANCER
CAT.# FP-059: RET GENE AMPLIFICATION PROBE
IVD/RUO
BACKGROUND
RET gene is located on the long arm of chromosome 10 and encodes a receptor tyrosine kinase. It is expressed in normal neurons, sympathetic and parasympathetic ganglia, thyroid C cells, adrenal myelocytes, genitourinary tract cells, and testicular germ cells. Activation of the RET protein activates downstream signaling pathways (including RAS, MAPK, ERK, PI3K, AKT, etc.), resulting in cell proliferation, migration, and differentiation. Activating mutations in the RET gene are associated with human malignancies, but if the RET gene loses its function, this can lead to gastrointestinal developmental diseases such as the congenital megacolon or Hirschsprung’s disease.
PROBE DESCRIPTION
The RET gene break-apart probe uses an orange-red dye to label the RET gene (5′-end) region, and a green dye to label the RET gene (3′-end) region. The RET gene break-apart probe detects all RET gene rearrangements, avoiding missed diagnosis by a single gene fusion.
CLINICAL SIGNIFICANCE
RET gene fusion in patients with non-small cell lung cancer accounts for 1%-2% of the frequency, and the RET gene is mutually exclusive with other driver genes such as EGFR, KRAS, ALK, HER2 and BRAF, i.e., rarely occurs at the same time, the RET gene is an independent gene for driving non-small cell lung cancer. At present, there are four fusion partner genes of RET gene, namely KIF5B, CCDC6, TRIM33 and NCOA4, of which KIF5B is the most important fusion gene, accounting for 90%.
RET gene fusion is more common in patients who have never smoked or had adenocarcinoma. Screening of 936 patients with non-small cell lung cancer found 13 patients with positive RET fusion genes, 11 of which were adenocarcinomas (85% probability), and other characteristics of the patients included never smoking, and being younger. Moreover, the primary lesions of these patients are often smaller (100%, less than 3 cm).
References
- Takashi Kohno, et al., Transl Lung Cancer Res. 2015 Apr;4(2):156-64.
- Drilon A, et al., Ann Oncol. 2016 Jul;27(7):1286-91.
- Falchook GS, et al., J Clin Oncol. 2016 May 20;34(15):e141-4
