RET FISH

RET gene rearrangements that result in growth-promoting chimeric or fusion proteins are found in 1-2% of adenocarcinoma-containing non-small cell lung cancer (NSCLC) and 20-40% of sporadic papillary thyroid carcinoma (PTC). In lung cancer, the most common rearrangement partner is KIF5B, followed by PTC1 and PTC3 rearrangements which are the most common in PTC. RET rearrangements in NSCLC are generally mutually exclusive of mutations in EGFR, KRAS, ALK, and ROS1. Patients tend to be younger (<60) and lack smoking history. Early clinical studies in NSCLC show response to multi-kinase inhibitors. By identifying PTC, RET rearrangements are one of several genetic markers useful for classifying indeterminate thyroid FNA cytology results. Sequence-variant mutations in the RET gene associated with MEN2 syndrome or sporadic medullary thyroid carcinoma (MTC) will not be detected by FISH; next-gen sequencing for the RET gene may be considered instead.