Abstract
Purpose
Genomic alterations are fundamental for molecular-guided therapy in patients with breast and lung cancer. However, the turn-around time of standard next-generation sequencing assays is a limiting factor in the timely delivery of genomic information for clinical decision-making.
Methods
In this study, we evaluated genomic alterations in 54 cerebrospinal fluid samples from 33 patients with metastatic lung cancer and metastatic breast cancer to the brain using the Oncomine Precision Assay on the Genexus sequencer. There were nine patients with samples collected at multiple time points.
Results
Cell-free total nucleic acids (cfTNA) were extracted from CSF (0.1–11.2 ng/μl). Median base coverage was 31,963× with cfDNA input ranging from 2 to 20 ng. Mutations were detected in 30/54 CSF samples. Nineteen (19/24) samples with no mutations detected had suboptimal DNA input (< 20 ng). The EGFR exon-19 deletion and PIK3CA mutations were detected in two patients with increasing mutant allele fraction over time, highlighting the potential of CSF-cfTNA analysis for monitoring patients. Moreover, the EGFR T790M mutation was detected in one patient with prior EGFR inhibitor treatment. Additionally, ESR1 D538G and ESR1::CCDC170 alterations, associated with endocrine therapy resistance, were detected in 2 mBC patients. The average TAT from cfTNA-to-results was < 24 h.
Conclusion
In summary, our results indicate that CSF-cfTNA analysis with the Genexus-OPA can provide clinically relevant information in patients with brain metastases with short TAT.
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Data availability
All data generated or analyzed during this study are included in this published article.
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Funding
Research reported in this publication was partially supported by the National Cancer Institute of the National Institutes of Health under award number K08CA241651 and this work was partly supported by the generous philanthropic contributions to The University of Texas MD Anderson Cancer Center Glioblastoma Moon Shots Program™. This work was partially supported by an Oncomine Clinical Research Grant from Thermo Fisher Scientific (awarded to LYB).
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Authors and Affiliations
Contributions
JJZ, SRC, FL and YE—contributed to sample collection. AD, YE, JJZ—patient consent. MS and AD—performed sample processing and cfDNA extraction. SA—performed NGS experiments and prepared initial manuscript draft. PP and LN—performed sample annotation and collection of clinical information. DW-contributed to the preparation of figures and data analysis. LB, RL, DD and YE—Project conception, experimental design and manuscript writing. All authors reviewed and approved the manuscript.
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The authors have no relevant financial or non-financial interests to disclose. The authors have no competing interests to declare that are relevant to the content of this article. All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript. The authors have no financial or proprietary interests in any material discussed in this article.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the local ethics regulations and approvals and with the 1964 Helsinki declaration and its later amendments. All procedures were performed in accordance with local institutional review board (IRB MDACC and UTHealth) guidelines.
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Informed consent was obtained from all individual participants included in the study.
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11060_2023_4487_MOESM1_ESM.jpg
Supplementary fig 1: The overall survival of patients with positive and negative CSF-ctDNA results. (A) Survival analysis of patients with mLC. There were 10 patients with CSF ctDNA positive and 11 patients with CSF ctDNA negative results. The median survival was 37 months and 45 months for CSF ctDNA positive and CSF ctDNA negative patients, respectively. (B) Survival analysis of patients with mBC. There were 9 patients with CSF ctDNA positive and 3 with CSF ctDNA negative results. The median survival was undefined for both CSF ctDNA positive and CSF ctDNA negative mBC patients. Supplementary file1 (JPG 217 kb)
11060_2023_4487_MOESM2_ESM.jpg
Supplementary fig 2A–E: MRI results and CSF ctDNA results for patients with multiple CSF samples. (A) MRI results and CSF ctDNA results from mLC sample #1, (B) MRI results and CSF ctDNA results from mLC sample #3, (C) MRI results and CSF ctDNA results from mBC sample #2, (D) MRI results and CSF ctDNA results from mBC sample #5, (E) MRI results and CSF ctDNA results from mBC sample #6. Supplementary file2 (JPG 1129 kb)
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Arjuna, S., Shah, M., Dono, A. et al. Rapid detection of mutations in CSF-cfTNA with the Genexus Integrated Sequencer. J Neurooncol 166, 39–49 (2024). https://doi.org/10.1007/s11060-023-04487-0
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DOI: https://doi.org/10.1007/s11060-023-04487-0