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

Authors :
Jotaro On
Manabu Natsumeda
Jun Watanabe
Shoji Saito
Yu Kanemaru
Hideaki Abe
Yoshihiro Tsukamoto
Masayasu Okada
Makoto Oishi
Junichi Yoshimura
Akiyoshi Kakita
Yukihiko Fujii
Source :
Diagnostics, Vol 11, Iss 4, p 681 (2021)
Publication Year :
2021
Publisher :
MDPI AG, 2021.

Abstract

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 H3F3A K27M mutation using digital droplet PCR. In 10 patients, CSF was obtained by lumbar puncture at presentation. A definitive detection of H3F3A K27M mutation was achieved in only one case (10%); H3F3A K27M mutation was suspected in three other cases (30%). H3F3A 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 H3F3A K27M or definite H3F3A wildtype) tended to be younger (median 7.5 years vs. 40.5 years; p = 0.07) and have a higher concentration of CSF protein (median 123 mg/dL vs. 27.5 mg/dL; p = 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.

Details

Language :
English
ISSN :
20754418
Volume :
11
Issue :
4
Database :
Directory of Open Access Journals
Journal :
Diagnostics
Publication Type :
Academic Journal
Accession number :
edsdoj.8186a349fab843a49a1a12cceba0ec0b
Document Type :
article
Full Text :
https://doi.org/10.3390/diagnostics11040681