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:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85067217817&doi=10.1158%2f1535-7163.MCT-18-1244&partnerID=40&md5=14aacb4180e7476fe559fdbc2dd6cadb
Notes:	Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/147530