Molecular profiling of tumor tissue and plasma cell-free DNA from patients with non-langerhans cell histiocytosis Journal Article


Authors: Janku, F.; Diamond, E. L.; Goodman, A. M.; Raghavan, V. K.; Barnes, T. G.; Kato, S.; Abdel-Wahab, O.; Durham, B. H.; Meric-Bernstam, F.; Kurzrock, R.
Article Title: Molecular profiling of tumor tissue and plasma cell-free DNA from patients with non-langerhans cell histiocytosis
Abstract: The BRAFV600E 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 BRAFV600E 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 BRAFV600E mutation. Of 31 patients evaluable for non-BRAFV600E alterations, 18 (58%) had ≥1 alteration and 12 putative non-BRAFV600E 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. ©2019 American Association for Cancer Research.
Journal Title: Molecular Cancer Therapeutics
Volume: 18
Issue: 6
ISSN: 1535-7163
Publisher: American Association for Cancer Research  
Date Published: 2019-06-01
Start Page: 1149
End Page: 1157
Language: English
DOI: 10.1158/1535-7163.Mct-18-1244
PUBMED: 31015311
PROVIDER: scopus
PMCID: PMC6548628
DOI/URL:
Notes: Source: Scopus
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  1. Eli Louis Diamond
    203 Diamond
  2. Benjamin Heath Durham
    115 Durham