Clinically Relevant Mutations Identified Through Sequencing of Cerebrospinal Fluid of Patients With CNS Cancers


Key Points

  • Somatic alterations were found in the cerebrospinal fluid of the majority of patients with CNS metastases or primary brain tumors.
  • Resistance mutations were identified in patients with progressive CNS disease during treatment with kinase inhibitors.

Next-generation sequencing identified clinically relevant somatic alterations in cancer-associated genes in the cerebrospinal fluid of patients with central nervous system (CNS) cancers, according to a report by Pentsova et al in the Journal of Clinical Oncology.

Somatic Alterations

The study involved next-generation sequencing for 341 genes in cell-free DNA from cerebrospinal fluid obtained with routine lumbar puncture in 53 patients with cancer who had suspected or known CNS involvement. High-confidence somatic alterations were found in 20 (63%) of 32 patients with CNS metastases of solid tumors, 6 (50%) of 12 patients with primary brain tumors, and 0 (0%) of 9 patients without CNS involvement.

Mutation Patterns

Among 12 patients who developed progressive CNS disease during treatment with oncogenic kinase inhibitors, established drug-resistance mutations were found in the cerebrospinal fluid of 4 patients, and candidate drug-resistance mutations were found in another two patients. Assessment of patients with glioma identified patterns of alterations suggestive of tumor-evolution convergence on the PI3K pathway during progression and mutation patterns associated with temozolomide resistance.

The investigators concluded: “The study shows that cerebrospinal fluid harbors clinically relevant genomic alterations in patients with CNS cancers and should be considered for liquid biopsies to monitor tumor evolution in the CNS.”

The study was supported by the National Institutes of Health, Memorial Sloan Kettering Brain Tumor Center, Defeat GBM Initiative of the National Brain Tumor Society, and Marie-Josée and Henry R. Kravis Center for Molecular Oncology.

Ingo K. Mellinghoff, MD, of Memorial Sloan Kettering Cancer Center, New York, is the corresponding author of the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.