An Alert to Possible False Positives With a Commercial Assay for MET Exon 14 Skipping
| Autor: | Takashi Teishikata, Yasushi Yatabe, Yuki Shinno, Takako Ishiyama, Jumpei Kashima, Yoshihisa Kobayashi, Taisuke Mori, Tatsuya Yoshida, Kouya Shiraishi |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Pulmonary and Respiratory Medicine
Oncology medicine.medical_specialty Lung Neoplasms Capmatinib business.industry Exons Proto-Oncogene Proteins c-met Clinical trial Exon Splice Donor Site Carcinoma Non-Small-Cell Lung Internal medicine Mutation False positive paradox Humans Medicine In patient business |
| Zdroj: | Journal of Thoracic Oncology. 16:2133-2138 |
| ISSN: | 1556-0864 |
| DOI: | 10.1016/j.jtho.2021.07.028 |
| Popis: | Introduction Because molecular-targeted drugs against MET exon 14 (METex14) skipping have been approved, molecular testing of the alteration has added to clinical guidelines. There are several such assays, but methodological issues have been reported. Methods METex14 skipping results from three assays (Oncomine DxTT, ArcherMET, and laboratory-developed reverse-transcriptase polymerase chain reaction test [LDT RT-PCR]) were compared in a relatively small series of the specimens diagnosed as advanced NSCLC (n = 50). Results The ArcherMET and LDT RT-PCR results were identical for all 50 samples, but eight samples had discordant results between Oncomine DxTT and the other two assays. All eight samples had METex14 skipping with Oncomine DxTT and wild-type signals with ArcherMET and LDT RT-PCR. The discordance might be caused by the homopolymeric error of the splice donor site with Oncomine DxTT, and false positives could be distinguished by relatively low read counts. Conclusions Although the caution in detecting METex14 skipping focuses on false negatives in the literature, false positives were first noted at a relatively high frequency (8 of 26, 30.8%) in this study. According to the results of previous clinical trials using the other tyrosine kinase inhibitors, it could be surmised that MET inhibitor treatment in patients without METex14 skipping is detrimental. Clinicians need to be alert to the false positives that can lead to harmful treatments. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|