Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center Houston, Houston, TX, USA.
Vivian L. Smith Department of Neurosurgery, McGovern Medical School at UT Health, Houston, TX, USA.
J Neurooncol. 2024 Jan;166(1):39-49. doi: 10.1007/s11060-023-04487-0. Epub 2023 Dec 30.
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.
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.
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.
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.
基因组改变是指导乳腺癌和肺癌患者分子靶向治疗的基础。然而，标准下一代测序检测的周转时间是及时提供基因组信息以进行临床决策的一个限制因素。
本研究中，我们使用 Genexus 测序仪上的 Oncomine Precision 检测评估了 33 例转移性肺癌和转移性乳腺癌脑转移患者的 54 份脑脊液样本中的基因组改变。其中 9 例患者的样本采集时间点多于一个。
从 CSF 中提取了无细胞总核酸（cfTNA）（0.1-11.2ng/μl）。cfDNA 输入范围为 2 至 20ng 时，中位碱基覆盖率为 31963×。30/54 份 CSF 样本中检测到突变。19/24 份未检测到突变的样本 DNA 输入量不足（<20ng）。两名患者的 EGFR 外显子 19 缺失和 PIK3CA 突变随着时间的推移逐渐增加，表明 CSF-cfTNA 分析有监测患者的潜力。此外，一名接受过 EGFR 抑制剂治疗的患者中检测到 EGFR T790M 突变。此外，在 2 名 mBC 患者中检测到与内分泌治疗耐药相关的 ESR1 D538G 和 ESR1::CCDC170 改变。cfTNA 到结果的平均 TAT<24 小时。
总之，我们的研究结果表明，使用 Genexus-OPA 的 CSF-cfTNA 分析可以在具有短 TAT 的脑转移患者中提供具有临床意义的信息。
