Erdheim-Chester Disease Due to a Novel Internal Duplication of NRAS: Response to Targeted Therapy with Cobimetinib

Histiocytoses encompass a group of exceptionally rare disorders characterized by the abnormal infiltration of tissues by histocytes. Among these, Erdheim-Chester disease (ECD) stands out as a multisystem histiocytosis that typically affects bones and various other tissues. Historically, the treatmen...

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Bibliographic Details
Published in:International journal of molecular sciences 2023-10, Vol.24 (20), p.15467
Main Authors: Riancho, José A, Hernández, José L, González-Vela, Carmen, López-Sundh, Ana E, González-Lopez, Marcos A, Gomez de la Fuente, Francisco, Quirce, Remedios, Diamond, Eli L
Format: Article
Language:English
Subjects:
Antimitotic agents
Antineoplastic agents
Autoimmune diseases
Biopsy
Bones
Case Report
Drug dosages
Erdheim-Chester Disease - drug therapy
Erdheim-Chester Disease - genetics
GTP Phosphohydrolases - genetics
Humans
Interferon
Kinases
Membrane Proteins - genetics
Mutation
Patients
Phosphorylation
Proteins
Proto-Oncogene Proteins B-raf - genetics
Skin
Tumors
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Summary:Histiocytoses encompass a group of exceptionally rare disorders characterized by the abnormal infiltration of tissues by histocytes. Among these, Erdheim-Chester disease (ECD) stands out as a multisystem histiocytosis that typically affects bones and various other tissues. Historically, the treatment of ECD has been challenging. However, recent breakthroughs in our understanding, particularly the discovery of somatic mutations in the RAS-MAPK pathway, have opened new opportunities for targeted therapy in a significant subset of patients with ECD and other histiocytoses. In this report, we present the case of a patient with ECD harboring a previously unidentified microduplication in the NRAS gene in a small fraction of skin cells. This discovery played a pivotal role in tailoring an effective therapeutic approach involving kinase inhibitors downstream of NRAS. This case underscores the crucial role of deep sequencing of tissue samples in ECD, enabling the delivery of personalized targeted therapy to patients.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms242015467