RET Fusions Define a Unique Molecular and Clinicopathologic Subtype of Non–Small-Cell Lung Cancer

Abstract

RET fusion occurs in 1.4% of NSCLCs and 1.7% of lung adenocarcinomas and has identifiable clinicopathologic characteristics, warranting further clinical consideration and targeted therapy investigation.

Analytical Validation of BRAF Mutation Testing from Circulating Free DNA Using the Amplification Refractory Mutation Testing System

“…This statement is evidence based and supported by 3 studies, 37,62,63 consisting of 1 PCS 62 and 2 RCSs. 37,63 All included studies were assessed for quality and none were found to have methodologic flaws that would raise concerns about the studies' findings (SDC Table 12).…”

“…62,64,65 RET fusion occurs more frequently in never smokers than ever smokers. 37,62,64,66,72 Patients with RET fusion harboring tumors are usually younger than patients with an EGFR mutation and have an equal gender distribution. 67 RET fusion proteins have been detected in adenocarcinoma 37,62,64 and in adenosquamous carcinoma.…”

“…37,62,64,66,72 Patients with RET fusion harboring tumors are usually younger than patients with an EGFR mutation and have an equal gender distribution. 67 RET fusion proteins have been detected in adenocarcinoma 37,62,64 and in adenosquamous carcinoma. 62 Histologic subtypes in adenocarcinomas include those with mucinous/signet ring cells and those with a cribriform 37,62,65 or solid growth pattern.…”

“…62 Histologic subtypes in adenocarcinomas include those with mucinous/signet ring cells and those with a cribriform 37,62,65 or solid growth pattern. 37,62 However, no clinical or histologic features (other than excluding from testing pure squamous histology cases) should be used to select a patient for RET testing.…”

“…37 Similar to ALK rearrangement testing by FISH, the threshold for RET FISH positivity for rearrangement is 15% of cells with split signals or single 3 0 probe signals. In another study, a 4-colored RET FISH assay was used 62 ; samples were positive for RET rearrangement or KIF5B-RET fusion if more than 20% of tumor cells exhibited split red-green signals or touching golden-green signals, respectively.…”