Erdheim–Chester disease due to a novel internal duplication of NRAS: Response to targeted therapy with cobimetinib Journal Article
| Authors: | Riancho, J. A.; Hernández, J. L.; González-Vela, C.; López-Sundh, A. E.; González-Lopez, M. A.; Gomez de la Fuente, F.; Quirce, R.; Diamond, E. L. |
| Article Title: | Erdheim–Chester disease due to a novel internal duplication of NRAS: Response to targeted therapy with cobimetinib |
| Abstract: | 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. © 2023 by the authors. |
| Keywords: | genetics; mutation; case report; membrane proteins; membrane protein; targeted therapy; histiocytosis; b raf kinase; proto-oncogene proteins b-raf; gtp phosphohydrolases; guanosine triphosphatase; kinase inhibitors; nras; humans; human; erdheim chester disease; erdheim-chester disease; cobimetinib; nras protein, human; erdheim–chester disease |
| Journal Title: | International Journal of Molecular Sciences |
| Volume: | 24 |
| Issue: | 20 |
| ISSN: | 1422-0067 |
| Publisher: | MDPI |
| Date Published: | 2023-10-02 |
| Start Page: | 15467 |
| Language: | English |
| DOI: | 10.3390/ijms242015467 |
| PUBMED: | 37895147 |
| PROVIDER: | scopus |
| PMCID: | PMC10606995 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding author is MSK author: Eli L. Diamond -- Source: Scopus |
