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Mol Cancer Ther. 2019 Jun;18(6):1149-1157. doi: 10.1158/1535-7163.MCT-18-1244. Epub 2019 Apr 23.

Molecular Profiling of Tumor Tissue and Plasma Cell-Free DNA from Patients with Non-Langerhans Cell Histiocytosis.

Author information

1
Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), Division of Cancer Medicine, The University of Texas, MD Anderson Cancer Center, Houston, Texas. fjanku@mdanderson.org diamone1@mskcc.org.
2
Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York. fjanku@mdanderson.org diamone1@mskcc.org.
3
Center for Personalized Cancer Therapy, Division of Blood and Marrow Transplantation, Division of Hematology/Oncology, Department of Medicine, University of California San Diego, Moores Cancer Center, La Jolla, California.
4
Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), Division of Cancer Medicine, The University of Texas, MD Anderson Cancer Center, Houston, Texas.
5
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
6
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
#
Contributed equally

Abstract

The BRAF V600E mutation and BRAF inhibitor responsiveness characterize ∼50% of patients with the non-Langerhans cell histiocytosis (non-LCH) Erdheim-Chester disease (ECD). We interrogated the non-LCH molecular landscape [ECD, n = 35; Rosai-Dorfman disease (RDD), n = 3; mixed ECD/RDD, n = 1] using BRAF V600E PCR and/or next-generation sequencing [tissue and cell-free DNA (cfDNA) of plasma and/or urine]. Of 34 evaluable patients, 17 (50%) had the BRAF V600E mutation. Of 31 patients evaluable for non-BRAF V600E alterations, 18 (58%) had ≥1 alteration and 12 putative non-BRAF V600E MAPK pathway alterations: atypical BRAF mutation; GNAS, MAP2K1, MAP2K2, NF1, and RAS mutations; RAF1 or ERBB2 amplifications; LMNA-NTRK1 (TRK inhibitor-sensitive) and CAPZA2-BRAF fusions. Four patients had JAK2, MPL ASXL1, U2AF1 alterations, which can correlate with myeloid neoplasms, a known ECD predisposition, and one developed myelofibrosis 13 months after cfDNA testing. Therefore, our multimodal comprehensive genomics reveals clinically relevant alterations and suggests that MAPK activation is a hallmark of non-LCH.

PMID:
31015311
PMCID:
PMC6548628
[Available on 2020-06-01]
DOI:
10.1158/1535-7163.MCT-18-1244
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