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GENOMICS AND GENE THERAPY

The potential of cell-free DNA to reveal the molecular profiles of Langerhans cell histiocytosis and Erdheim–Chester disease in adults

Leukemia volume 36, pages 1412–1415 (2022)Cite this article

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To the Editor:

Histiocytosis is a rare kind of hematologic neoplasm that arises from histiocytes and dendritic cells. Langerhans cell histiocytosis (LCH) and Erdheim–Chester disease (ECD) belong to the “L-group” of histiocytosis [1,2,3]. Although various studies have identified driver mutations in MAPK pathway in tumor tissues of LCH and ECD patients, sequencing of plasma cell-free DNA (cfDNA) is rare [4,5,6,7]. Plasma cfDNA is a promising supplement to tissue sequencing due to the difficulty to detect key driver mutations in the scant histiocytes and to obtain tissue samples of frequently involved organs. Furthermore, sequencing of plasma cfDNA in LCH has mainly focused on pediatric patients, but adult LCH patients tend to have a different prognosis and genetic landscape [8, 9]. Moreover, only BRAF mutations have been explored in cfDNA of LCH patients, and only one study has performed targeted next-generation sequencing (NGS) of cfDNA of ECD patients to explore genetic landscape besides the single BRAF gene [10]. Therefore, this study aimed to evaluate the role of cfDNA in detecting the molecular profile of adult LCH and ECD patients and to investigate concordance between cfDNA and tumor tissues.

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Fig. 1: Mutations detected in Langerhans cell histiocytosis and Erdheim-Chester disease.
Fig. 2: Mutations detected in tumor tissues and plasma cfDNA detected in Langerhans cell histiocytosis and Erdheim–Chester disease patients.

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Author notes

  1. These authors contributed equally: Ai-lin Zhao, Hao Cai.

Authors and Affiliations

  1. Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China

    Ai-lin Zhao, Hao Cai, Jia Chen, Ming-hui Duan, Dao-bin Zhou, Jian Li & Xin-xin Cao

  2. Department of Hematology, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China

    Ai-lin Zhao

  3. State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China

    Hao Cai, Jia Chen, Ming-hui Duan, Dao-bin Zhou, Jian Li & Xin-xin Cao

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  1. Ai-lin Zhao
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Contributions

ALZ was responsible for writing the protocol and report, conducting the research, screening potentially eligible patients, collecting the samples, extracting and analyzing data, interpreting results, and writing the manuscript. HC was responsible for designing the protocol, preparing the samples, analyzing and confirming data, interpreting results, and writing the manuscript. JC was responsible for revising the protocol and report, confirming and interpreting data, creating figures and supplementary tables, and revising manuscript. MHD, DBZ, and JL were responsible for designing the protocol, revising the report, screening eligible patients, interpreting results, and providing feedback on the report. XXC was responsible for designing and revising the protocol and report, conducting the research, collecting samples, analyzing and interpreting results, creating figures and tables, and revising manuscript.

Corresponding author

Correspondence to Xin-xin Cao.

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The authors declare no competing interests.

Ethics approval and consent to participate

This study was conducted in accordance with the Declaration of Helsinki, and has been approved by the ethics committee of our center. Informed consent was obtained from every participant.

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Zhao, Al., Cai, H., Chen, J. et al. The potential of cell-free DNA to reveal the molecular profiles of Langerhans cell histiocytosis and Erdheim–Chester disease in adults. Leukemia 36, 1412–1415 (2022). https://doi.org/10.1038/s41375-022-01523-2

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