TY - JOUR
T1 - Identification of ALK, ROS1, and RET fusions by a multiplexed mRNA-based assay in formalin-fixed, paraffin-embedded samples from advanced non-small-cell lung cancer patients
AU - Reguart, Noemí
AU - Teixidó, Cristina
AU - Giménez-Capitán, Ana
AU - Paré, Laia
AU - Galván, Patricia
AU - Viteri, Santiago
AU - Rodríguez, Sonia
AU - Peg, Vicente
AU - Aldeguer, Erika
AU - Viñolas, Nuria
AU - Remon, Jordi
AU - Karachaliou, Niki
AU - Conde, Esther
AU - Lopez-Rios, Fernando
AU - Nadal, Ernest
AU - Merkelbach-Bruse, Sabine
AU - Büttner, Reinhard
AU - Rosell, Rafael
AU - Molina-Vila, Miguel A.
AU - Prat, Aleix
N1 - Publisher Copyright:
© 2016 American Association for Clinical Chemistry.
PY - 2017/3/1
Y1 - 2017/3/1
N2 - Background: Anaplastic lymphoma receptor tyrosine kinase (ALK), ROS proto-oncogene 1, receptor tyrosine kinase (ROS1), and ret proto-oncogene (RET ) fusions are present in 5%-7% of patients with advanced non-small-cell lung cancer (NSCLC); their accurate identification is critical to guide targeted therapies. FISH and immunohistochemistry (IHC) are considered the gold standards to determine gene fusions, but they have limitations. The nCounter platform is a potentially useful genomic tool for multiplexed detection of gene fusions, but has not been validated in the clinical setting. Methods: Formalin-fixed, paraffin embedded (FFPE) samples from 108 patients with advanced NSCLC were analyzed with an nCounter-based assay and the results compared with FISH, IHC, and reverse transcription PCR(RTPCR). Data on response to fusion kinase inhibitors was retrospectively collected in a subset of 29 patients. Results: Of 108 FFPE samples, 98 were successfully analyzed by nCounter (91%), which identified 55 fusionpositive cases (32 ALK, 21 ROS1, and 2 RET ). nCounter results were highly concordant with IHC for ALK (98.5%, CI = 91.8-99.7), while 11 discrepancies were found compared with FISH (87.5% concordance, CI = 79.0-92.9). For ROS1, nCounter showed similar agreement with IHC and FISH (87.2% and 85.9%), but a substantial number of samples were positive only by 1 or 2 techniques. Of the 25 patients deriving clinical benefit from fusion kinase inhibitors, 24 were positive by nCounter and 22 by FISH. Conclusions: nCounter compares favorably with IHC and FISH and can be used for identifying patients with advanced NSCLC positive for ALK/ROS1/RET fusion genes.
AB - Background: Anaplastic lymphoma receptor tyrosine kinase (ALK), ROS proto-oncogene 1, receptor tyrosine kinase (ROS1), and ret proto-oncogene (RET ) fusions are present in 5%-7% of patients with advanced non-small-cell lung cancer (NSCLC); their accurate identification is critical to guide targeted therapies. FISH and immunohistochemistry (IHC) are considered the gold standards to determine gene fusions, but they have limitations. The nCounter platform is a potentially useful genomic tool for multiplexed detection of gene fusions, but has not been validated in the clinical setting. Methods: Formalin-fixed, paraffin embedded (FFPE) samples from 108 patients with advanced NSCLC were analyzed with an nCounter-based assay and the results compared with FISH, IHC, and reverse transcription PCR(RTPCR). Data on response to fusion kinase inhibitors was retrospectively collected in a subset of 29 patients. Results: Of 108 FFPE samples, 98 were successfully analyzed by nCounter (91%), which identified 55 fusionpositive cases (32 ALK, 21 ROS1, and 2 RET ). nCounter results were highly concordant with IHC for ALK (98.5%, CI = 91.8-99.7), while 11 discrepancies were found compared with FISH (87.5% concordance, CI = 79.0-92.9). For ROS1, nCounter showed similar agreement with IHC and FISH (87.2% and 85.9%), but a substantial number of samples were positive only by 1 or 2 techniques. Of the 25 patients deriving clinical benefit from fusion kinase inhibitors, 24 were positive by nCounter and 22 by FISH. Conclusions: nCounter compares favorably with IHC and FISH and can be used for identifying patients with advanced NSCLC positive for ALK/ROS1/RET fusion genes.
UR - http://www.scopus.com/inward/record.url?scp=85014439476&partnerID=8YFLogxK
U2 - 10.1373/clinchem.2016.265314
DO - 10.1373/clinchem.2016.265314
M3 - Article
C2 - 28073897
AN - SCOPUS:85014439476
SN - 0009-9147
VL - 63
SP - 751
EP - 760
JO - Clinical Chemistry
JF - Clinical Chemistry
IS - 3
ER -