RT Journal Article
T1 RET Fusion Testing in Patients With NSCLC: The RETING Study
A1 Conde Gallego, Esther
A1 Hernández, Susana
A1 Alonso, Marta
A1 Curto, Daniel
A1 Rojo, Federico
A1 Dómine, Manuel
A1 Paz-Ares Rodríguez, Luis Gonzaga
A1 López-Ríos Moreno, Fernando
AB IntroductionRET inhibitors with impressive overall response rates are now available for patients with NSCLC, yet the identification of RET fusions remains a difficult challenge. Most guidelines encourage the upfront use of next-generation sequencing (NGS), or alternatively, fluorescence in situ hybridization (FISH) or reverse transcriptase-polymerase chain reaction (RT-PCR) when NGS is not possible or available. Taken together, the suboptimal performance of single-analyte assays to detect RET fusions, although consistent with the notion of encouraging universal NGS, is currently widening some of the clinical practice gaps in the implementation of predictive biomarkers in patients with advanced NSCLC.MethodsThis situation prompted us to evaluate several RET assays in a large multicenter cohort of RET fusion–positive NSCLC (n = 38) to obtain real-world data. In addition to RNA-based NGS (the criterion standard method), all positive specimens underwent break-apart RET FISH with two different assays and were also tested by an RT-PCR assay.ResultsThe most common RET partners were KIF5B (78.9%), followed by CCDC6 (15.8%). The two RET NGS-positive but FISH-negative samples contained a KIF5B(15)-RET(12) fusion. The three RET fusions not identified with RT-PCR were AKAP13(35)-RET(12), KIF5B(24)-RET(9) and KIF5B(24)-RET(11). All three false-negative RT-PCR cases were FISH-positive, exhibited a typical break-apart pattern, and contained a very high number of positive tumor cells with both FISH assays. Signet ring cells, psammoma bodies, and pleomorphic features were frequently observed (in 34.2%, 39.5%, and 39.5% of tumors, respectively).ConclusionsIn-depth knowledge of the advantages and disadvantages of the different RET testing methodologies could help clinical and molecular tumor boards implement and maintain sensible algorithms for the rapid and effective detection of RET fusions in patients with NSCLC. The likelihood of RET false-negative results with both FISH and RT-PCR reinforces the need for upfront NGS in patients with NSCLC.
PB Elsevier
SN 2666-3643
YR 2024
FD 2024-02-20
LK https://hdl.handle.net/20.500.14352/118195
UL https://hdl.handle.net/20.500.14352/118195
LA eng
NO Esther Conde, Susana Hernandez, Jose Luis Rodriguez Carrillo, Rebeca Martinez, Marta Alonso, Daniel Curto, Beatriz Jimenez, Alejandra Caminoa, Amparo Benito, Pilar Garrido, Sergi Clave, Edurne Arriola, Isabel Esteban-Rodriguez, Javier De Castro, Irene Sansano, Enriqueta Felip, Federico Rojo, Manuel Dómine, Ihab Abdulkader, Jorge Garcia-Gonzalez, Cristina Teixido, Noemi Reguart, Desamparados Compañ, Amelia Insa, Nuria Mancheño, Sarai Palanca, Oscar Juan-Vidal, Nuria Baixeras, Ernest Nadal, Maria Cebollero, Antonio Calles, Paloma Martin, Clara Salas, Mariano Provencio, Ignacio Aranda, Bartomeu Massuti, Laura Lopez-Vilaro, Margarita Majem, Luis Paz-Ares, Fernando Lopez-Rios, RET Fusion Testing in Patients With NSCLC: The RETING Study, JTO Clinical and Research Reports, Volume 5, Issue 4, 2024, 100653, ISSN 2666-3643, https://doi.org/10.1016/j.jtocrr.2024.100653.
NO Fondos FEDERPlan Estatal I+D+I 2008–2011Plan Estatal I+D+I 2013–2016iLUNG Program
NO Eli Lilly
NO Fundacion de Investigacion HM Hospitales
NO Hospital Universitario 12 de Octubre
NO Fundacion Mutua Madrileña
NO Instituto de Salud Carlos III
NO Unión Europea
NO Comunidad Autónoma de Madrid
DS Docta Complutense
RD 10 abr 2025