Low Detection Rate of H3K27M Mutations in Cerebrospinal Fluid Obtained from Lumbar Puncture in Newly Diagnosed Diffuse Midline Gliomas

• Published in: Diagnostics (Basel) Vol. 11; no. 4; p. 681
• Main Authors: On, Jotaro, Natsumeda, Manabu, Watanabe, Jun, Saito, Shoji, Kanemaru, Yu, Abe, Hideaki, Tsukamoto, Yoshihiro, Okada, Masayasu, Oishi, Makoto, Yoshimura, Junichi, Kakita, Akiyoshi, Fujii, Yukihiko
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 09.04.2021; MDPI
• Subjects: Biopsy; Brain cancer; circulating tumor DNA; diagnosis; diffuse midline glioma; H3K27M-mutant; Hydrocephalus; liquid biopsy; Mutation; Nervous system; Patients; Plasma; Thermal cycling; diagnosis; H3K27M-mutant; diffuse midline glioma; liquid biopsy; circulating tumor DNA
• ISSN: 2075-4418; 2075-4418
• DOI: 10.3390/diagnostics11040681

Recent studies have suggested the feasibility of detecting H3K27M mutations in the cerebrospinal fluid of diffuse midline glioma (DMG) patients. However, cerebrospinal fluid from patients in these studies were collected mainly during biopsy, ventriculo-peritoneal shunt procedures or postmortem. We assessed circulating tumor DNA (ctDNA) extracted from cerebrospinal fluid (CSF) and plasma in a series of 12 radiographically suspected and/or pathologically confirmed diffuse midline glioma patients and assessed for K27M mutation using digital droplet PCR. In 10 patients, CSF was obtained by lumbar puncture at presentation. A definitive detection of K27M mutation was achieved in only one case (10%); K27M mutation was suspected in three other cases (30%). K27M mutation was detected in two patients in CSF obtained by ventricular tap during a ventriculo-peritoneal shunt for obstructive hydrocephalus. Cases in which a definitive assessment was possible (definite K27M or definite wildtype) tended to be younger (median 7.5 years vs. 40.5 years; = 0.07) and have a higher concentration of CSF protein (median 123 mg/dL vs. 27.5 mg/dL; = 0.21) compared to nondefinite cases. Low proliferation and apoptotic rates seemed to be characteristics of DMG unfavorable for liquid biopsy. More advanced lesions with necrosis and evidence of dissemination were unlikely to be candidates for lumbar puncture due to the fear of exacerbating obstructive hydrocephalus. Methods to safely sample CSF and a more sensitive detection of ctDNA are necessary for reliable liquid biopsy of DMG at presentation.