Highly sensitive fusion detection using plasma cell-free RNA in non-small-cell lung cancers.

Abstract

ALK, ROS1, and RET kinase fusions are important predictive biomarkers of tyrosine kinase inhibitors (TKIs) in non-small-cell lung cancer (NSCLC). Analysis of cell-free DNA (cfDNA) provides a noninvasive method to identify gene changes in tumor cells. The present study sought to use cfRNA and cfDNA for identifying fusion genes. A reliable protocol was established to detect fusion genes using cfRNA and assessed the analytical validity and clinical usefulness in 30 samples from 20 cases of fusion-positive NSCLC. The results of cfRNA-based assays were compared with tissue biopsy and cfDNA-based liquid biopsy (Guardant360 plasma next-generation sequencing [NGS] assay). The overall sensitivity of the cfRNA-based assay was 26.7% (8/30) and that of cfDNA-based assay was 16.7% (3/18). When analysis was limited to the samples collected at chemo-naïve or progressive disease status and available for both assays, the sensitivity of the cfRNA-based assay was 77.8% (7/9) and that of cfDNA-based assay was 33.3% (3/9). Fusion gene identification in cfRNA was correlated with treatment response. These results suggest that the proposed cfRNA assay is a useful diagnostic test for patients with insufficient tissues to facilitate effective administration of first-line treatment and is a useful tool to monitor the progression of NSCLC for consideration of second-line treatments.

• Authors: Nobuhiko Hasegawa, Shinji Kohsaka, Kana Kurokawa, Yuki Shinno, Ikuko Takeda Nakamura, Toshihide Ueno, Shinya Kojima, Masahito Kawazu, Yoshiyuki Suehara, Muneaki Ishijima, Yasushi Goto, Yuki Kojima, Kan Yonemori, Takuo Hayashi, Tsuyoshi Saito, Takehito Shukuya, Fumiyuki Takahashi, Kazuhisa Takahashi, Hiroyuki Mano
• Journal: Cancer science (Cancer Sci) Vol. 112 Issue 10 Pg. 4393-4403 (Oct 2021) ISSN: 1349-7006 [Electronic] England
• PMID: 34310819 (Publication Type: Comparative Study, Journal Article)
• Copyright: © 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Chemical References

• Biomarkers, Tumor
• Carbazoles
• Cell-Free Nucleic Acids
• Cytoskeletal Proteins
• EML4-ALK fusion protein, human
• KIF5B-ALK fusion protein, human
• Oncogene Proteins, Fusion
• Piperidines
• Protein Kinase Inhibitors
• Proto-Oncogene Proteins
• RNA, Messenger
• ezrin
• Crizotinib
• GAPDH protein, human
• Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)
• Anaplastic Lymphoma Kinase
• Protein-Tyrosine Kinases
• Proto-Oncogene Proteins c-ret
• RET protein, human
• ROS1 protein, human
• alectinib

Topics

• Adult
• Aged
• Aged, 80 and over
• Anaplastic Lymphoma Kinase (genetics)
• Biomarkers, Tumor (genetics)
• Biopsy
• Carbazoles (therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics, pathology)
• Cell-Free Nucleic Acids (isolation & purification)
• Crizotinib (therapeutic use)
• Cytoskeletal Proteins (genetics)
• Disease Progression
• Drug Resistance, Neoplasm (genetics)
• Female
• Gene Fusion
• Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) (genetics)
• High-Throughput Nucleotide Sequencing (methods)
• Humans
• Liquid Biopsy (methods)
• Lung (pathology)
• Lung Neoplasms (drug therapy, genetics, pathology)
• Male
• Middle Aged
• Oncogene Proteins, Fusion (genetics, isolation & purification)
• Piperidines (therapeutic use)
• Protein Kinase Inhibitors (therapeutic use)
• Protein-Tyrosine Kinases (genetics)
• Proto-Oncogene Proteins (genetics)
• Proto-Oncogene Proteins c-ret (genetics)
• RNA, Messenger (isolation & purification)
• Sensitivity and Specificity