title: Quantification of tumor-derived cell free DNA(cfDNA) by digital PCR (DigPCR) in cerebrospinal fluid of patients with BRAFV600 mutated malignancies.
abstract: Tumor-derived cell free DNA (cfDNA) can be detected in plasma. We hypothesized that mutated BRAF V600 cfDNA could be quantified in the cerebrospinal fluid (CSF) of patients with central nervous system (CNS) metastases. We collected CSF from patients with BRAF V600E or K-mutated melanoma (N=8) or BRAF V600E mutated Erdheim-Chester Disease (ECD) (N=3) with suspected central nervous system (CNS) involvement on the basis of neurological symptoms (10/11), MRI imaging (8/11), or both. Tumor-derived cfDNA was quantified by digital PCR in the CSF of 6/11 patients (range from 0.15-10.56 copies/μL). Conventional cytology was negative in all patients except in the two patients with markedly elevated levels of tumor-derived cfDNA. In 2 patients with serial measurements, CSF tumor-derived cfDNA levels reflected response to treatment or progressive disease. CSF tumor-derived cfDNA has the potential to serve as a diagnostic tool that complements MRI and may be more sensitive than conventional cytology.
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA.
authors.forename: Parisa
authors.initials: P
authors.lastname: Momtaz
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Pentsova
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA.
authors.forename: Omar
authors.initials: O
authors.lastname: Abdel-Wahab
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA.
authors.forename: Eli
authors.initials: E
authors.lastname: Diamond
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA.
authors.forename: David
authors.initials: D
authors.lastname: Hyman
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA.
authors.forename: Taha
authors.initials: T
authors.lastname: Merghoub
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA.
authors.forename: Daoqi
authors.initials: D
authors.lastname: You
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA.
authors.forename: Billel
authors.initials: B
authors.lastname: Gasmi
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA.
authors.forename: Agnes
authors.initials: A
authors.lastname: Viale
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA.|Department of Medicine, Weill Cornell Medical College, New York, USA.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Chapman
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000134:cerebrospinal fluid / Q000235:genetics*; D016543:Central Nervous System Neoplasms / Q000134:cerebrospinal fluid / Q000201:enzymology / Q000235:genetics* / Q000556:secondary; D000074141:Circulating Tumor DNA / Q000134:cerebrospinal fluid / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods*; D031249:Erdheim-Chester Disease / Q000134:cerebrospinal fluid / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008545:Melanoma / Q000134:cerebrospinal fluid / Q000201:enzymology / Q000235:genetics* / Q000556:secondary; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction / Q000379:methods*; D011237:Predictive Value of Tests; D048493:Proto-Oncogene Proteins B-raf / Q000134:cerebrospinal fluid / Q000235:genetics*; D012878:Skin Neoplasms / Q000134:cerebrospinal fluid / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D013129:Spinal Puncture
chemical_list: D014408:Biomarkers, Tumor; D000074141:Circulating Tumor DNA; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF mutated melanoma; cell free DNA; cerebrospinal fluid; digital PCR; erdheim-chester disease