Detection of BRAF V600E mutation in radiological Langerhans cell histiocytosis-associated neurodegenerative disease using droplet digital PCR analysis

• Published in: International journal of hematology Vol. 118; no. 1; pp. 119 - 124
• Main Authors: Shimizu, Soichiro, Sakamoto, Kenichi, Kudo, Ko, Morimoto, Akira, Shioda, Yoko
• Format: Journal Article
• Language: English
• Published: Singapore Springer Nature Singapore 01-07-2023; Springer Nature B.V
• Subjects: Alleles; Asymptomatic; Autoimmune diseases; Deoxyribonucleic acid; Diabetes insipidus; Diabetes mellitus; DNA; Droplets; Gene frequency; Health risks; Hematology; Histiocytosis; Lesions; Leukocytes (mononuclear); Medical imaging; Medicine; Medicine & Public Health; Mutants; Mutation; Neurodegenerative diseases; Oncology; Original Article; Peripheral blood mononuclear cells; Polymerase chain reaction; Signs and symptoms; V600E; Digital droplet PCR; Neurodegenerative disease; Langerhans cell histiocytosis; BRAF V600E
• ISSN: 0925-5710; 1865-3774
• DOI: 10.1007/s12185-023-03588-w

Langerhans cell histiocytosis-associated neurodegenerative disease (LCH-ND) is the most serious late complication secondary to LCH and is gradually progressive, destructive, and irreversible. Detection of the
BRAF
V600E mutation in peripheral blood mononuclear cells (PBMCs), even in the absence of active LCH lesions, is considered a sign of clinical LCH-ND, presenting with both abnormal imaging findings and neurological symptoms. However, the detection of the
BRAF
V600E mutation in PBMCs of patients with asymptomatic radiological LCH-ND (rLCH-ND) without active LCH lesions who present only with abnormal imaging findings is unknown. In this study, we analyzed the
BRAF
V600E mutations in PBMCs and cell-free DNA (cfDNA) of patients with rLCH-ND without active LCH lesions (
n
 = 5) using a droplet digital polymerase chain reaction (ddPCR) assay. The
BRAF
V600E mutation in PBMCs was detected in three out of five (60%) cases. The mutant allele frequencies in the three positive cases were 0.049%, 0.027%, and 0.015%, respectively. However, the cfDNA
BRAF
V600E mutation remained undetected in all patients. Detection of the
BRAF
V600E mutant allele in PBMCs may be helpful in identifying asymptomatic rLCH-ND in patients at high risk for developing LCH-ND, including those with relapses at CNS risk sites or central diabetes insipidus.