Rapid Tumor DNA Analysis of Cerebrospinal Fluid Accelerates Treatment of Central Nervous System Lymphoma.
Mihir GuptaJoseph D BradleyElie MassaadEvan BurnsN Zeke GeorgantasGarrett MaronJulie BattenAidan GallagherJulia ThieraufNaema NayyarAmanda GordonSooAe JonesMichelle PisapiaYing SunPamela Stuart JonesFred G BarkerWilliam T CurryRajiv GuptaJavier RomeroNancy WangPriscilla BrastianosMaria Martinez-LageKensuke TateishiDeborah Anne ForstBrian Vala NahedTracy T BatchelorLauren L RitterhouseFlorian IserTobias KesslerJustin T JordanJorg DietrichMatthew L MeyersonDaniel P CahillJochen K LennerzBob CarterGanesh M ShankarPublished in: Blood (2024)
Delays and risks associated with neurosurgical biopsies preclude timely diagnosis and treatment of central nervous system (CNS) lymphoma and other CNS neoplasms. We prospectively integrated targeted rapid genotyping of cerebrospinal fluid (CSF) into the evaluation of 70 patients with CNS lesions of unknown etiology. Participants underwent genotyping of CSF-derived DNA using a qPCR-based approach for parallel detection of single-nucleotide variants in the MYD88, TERT promoter, IDH1, IDH2, BRAF and H3F3A genes within 80 minutes of sample acquisition. Canonical mutations were detected in 42% of patients with neoplasms, including cases of primary and secondary CNS lymphoma, glioblastoma, IDH-mutant brainstem glioma and H3K27M-mutant diffuse midline glioma. Genotyping results eliminated the need for surgical biopsies in 7/33 (21.2%) cases of newly diagnosed neoplasms, resulting in significantly accelerated initiation of disease-directed treatment (median 3 vs 12 days; p = 0.027). This assay was then implemented in a Clinical Laboratory Improvement Amendments (CLIA) environment, with 2-day median turnaround for diagnosis of central nervous system lymphoma from 66 patients across 4 clinical sites. Our study prospectively demonstrates that targeted rapid CSF genotyping influences oncologic management for suspected CNS tumors.
Keyphrases
- cerebrospinal fluid
- newly diagnosed
- genome wide
- high throughput
- wild type
- diffuse large b cell lymphoma
- blood brain barrier
- loop mediated isothermal amplification
- low grade
- dna methylation
- end stage renal disease
- circulating tumor
- single molecule
- gene expression
- genetic diversity
- chronic kidney disease
- cancer therapy
- pulmonary embolism
- prognostic factors
- transcription factor
- copy number
- risk assessment
- prostate cancer
- peritoneal dialysis
- inflammatory response
- human health
- drug delivery
- toll like receptor
- single cell
- bioinformatics analysis