Rapid Detection of Mutations in CSF-cfTNA With the Genexus Integrated Sequencer

Authors

Srividya Arjuna
Mauli Shah
Antonio Dono
Luis Nunez-Rubiano
Pavel S Pichardo-Rojas
Jay-Jiguang Zhu
Roy F Riascos
Rajyalakshmi Luthra
Sinchita Roy-Chowdhuri
Dzifa Duose
Daniel H Wang
Frederick F Lang
Yoshua Esquenazi
Leomar Y Ballester

Publication Date

1-1-2024

Journal

Journal of Neuro-Oncology

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.

Keywords

Humans, Lung Neoplasms, Cell-Free Nucleic Acids, Mutation, ErbB Receptors, Protein Kinase Inhibitors, CSF, ctDNA, cfDNA, Genexus, Liquid biopsy, Brain metastases, Lung cancer, Breast cancer, Cerebrospinal fluid

DOI

10.1007/s11060-023-04487-0

PMID

38160230

PMCID

PMC11264431

PubMedCentral® Posted Date

1-1-2025

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes