Detection of ALK fusion transcripts in plasma of non-small cell lung cancer patients using a novel RT-PCR based assay
(2021) Annals of Translational Medicine — Vol. 9, n° 11, p. 922 (2021)
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- Background: Detection of genomic rearrangements, like anaplastic lymphoma kinase (ALK) fusions, is a pivotal requirement in non-small cell lung cancer (NSCLC) for the initiation of a targeted treatment. While tissue testing remains the gold standard, detection of these alterations using liquid biopsies is an unmet need. To enable the detection of ALK rearrangements from circulating-free RNA (cfRNA) from NSCLC patients, we have evaluated a novel reverse transcription PCR (RT-PCR) based assay. Methods: Sixty-six patients with advanced stage NSCLC were included in the study. ALK status was determined by immunohistochemistry (IHC) and/or FISH on tissue sections. For the detection of ALK rearrangements from 2ml plasma collected in EDTA or Streck BCT DNA tubes, cfRNA was extracted using a prototype cfRNA sample preparation method and tested by a novel multiplex ALK/RET RT-PCR assay (Roche). Results: Of the forty-two patients with an ALK rearrangement, 30 (71%) were included at baseline. In 10 of the baseline patients, an ALK rearrangement was detected by RT-PCR [baseline sensitivity 33.33% (95% CI: 17.29-52.81%)]. All 24 negative ALK IHC/FISH-negative patients were negative using the RT-PCR based assay (specificity =100%). Conclusions: The prototype Roche ALK/RET RT-PCR assay was able to detect ALK fusion transcripts in the plasma of NSCLC patients at baseline as well as at disease progression with limited sensitivity but high specificity. Consequently, this assay could potentially be considered to select patients for an ALK-targeting therapy when tissue samples are lacking. Keywords: Non-small cell lung cancer (NSCLC); anaplastic lymphoma kinase (ALK); circulating free RNA (cfRNA); liquid biopsy; reverse transcription PCR (RT-PCR).
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Heeke, S., Benzaquen, J., Vallee, A., Allegra, M., Mazieres, J., Fayada, J., Rajamani, J., Lee, M., Ordinario, E., Tiotiu-Cepuc, I., Cadranel, J., Poudenx, M., Moro-Sibilot, D., Barlesi, F., Gervais, R., Thariat, J., Tanga, V., Boutros, J., Ilié, M., et al. (2021). Detection of ALK fusion transcripts in plasma of non-small cell lung cancer patients using a novel RT-PCR based assay. Annals of Translational Medicine, 9(11), 922. https://doi.org/10.21037/atm-20-7900 (Original work published 2021)