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

• Published in: International journal of molecular sciences Vol. 24; no. 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: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.10.2023; MDPI
• Subjects: Antimitotic agents; Antineoplastic agents; Autoimmune diseases; Biopsy; Bones; Case Report; cobimetinib; Drug dosages; Erdheim-Chester Disease - drug therapy; Erdheim-Chester Disease - genetics; Erdheim–Chester disease; GTP Phosphohydrolases - genetics; histiocytosis; Humans; Interferon; kinase inhibitors; Kinases; Membrane Proteins - genetics; Mutation; NRAS; Patients; Phosphorylation; Proteins; Proto-Oncogene Proteins B-raf - genetics; Skin; targeted therapy; Tumors; Spain; targeted therapy; NRAS; kinase inhibitors; cobimetinib; Erdheim–Chester disease; histiocytosis
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms242015467

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.