TY - JOUR
T1 - Molecular profiling of tumor tissue and plasma cell-free DNA from patients with non-Langerhans cell histiocytosis
AU - Janku, Filip
AU - Diamond, Eli L.
AU - Goodman, Aaron M.
AU - Raghavan, Vaijayanthi Kandadai
AU - Barnes, Tamara G.
AU - Kato, Shumei
AU - Abdel-Wahab, Omar
AU - Durham, Benjamin H.
AU - Meric-Bernstam, Funda
AU - Kurzrock, Razelle
N1 - Funding Information:
This work was supported by the Sidney Kimmel Foundation for Cancer Research (to F. Janku), the Sheikh Khalifa Al Nahyan Ben Zayed Institute for Personalized Cancer Therapy (to F. Janku), the ECD Global Alliance Grant (to
Funding Information:
F. Janku reports receiving a commercial research grant from Novartis, Genentech, Asana, Usher-Smith Laboratories, Bayer, FujiFilm Corporation, BioMed Valley Discoveries, Astellas, Agios, Plexxikon, Deciphera, Piqur, Sym-phogen, and Bristol-Myers Squibb; has ownership interest (including stock, patents, etc.) from Trovagene; and is a consultant/advisory board member of Guardant Health, IFM Therapeutics, Synlogic, Deciphera, Trovagene, and Immunomet. O. Abdel-Wahab reports receiving a commercial research grant from H3B Biomedicine; and is a consultant/advisory board member of Janssen, H3B Biomedicine, Merck, and Foundation Medicine Inc. F. Meric-Bernstam reports receiving a commercial research grant from Novartis, AstraZeneca, Zymework, PUMA Biotechnology, Curis, Pfizer, Daiichi Sankyo, Abbive, Guardant Health, Taiho, Genentech, Calithera, Debio, Bayer, Jounce, CytoMx, and eFFECTOR; and is a consultant/advisory board member of Debio, PUMA Biotechnology, Spectrum, Samsung Bioepis, Aduro, OrigiMed, Xencor, Jackson Laboratory, Mersana, Pfizer, Inflection Biosciences, Pieris, Darwin Health, GRAIL, Clearlight Diagnostics, Dialectica, AND Sumitomo Dainippon. R. Kurzrock has equity interest at IDbyDNA, CureMatch, Inc., and Soluventis; reports receiving a commercial research grant from Incyte, Genentech, Merck Serono, Pfizer, Sequenom, Foundation Medicine, Guardant Health, Grifols, Konica Minolta, and OmniSeq; has received speakers bureau honoraria from Roche; and has ownership interest (including stock, patents, etc.) from IDbyDNA, CureMatch, Inc., and Soluventis; and is a consultant/advisory board member of Gaido, LOXO, X-Biotech, Actuate Therapeutics, Roche, and NeoMed. No conflicts of interest were disclosed by the other authors.
Funding Information:
This work was supported by the Sidney Kimmel Foundation for Cancer Research (to F. Janku), the Sheikh Khalifa Al Nahyan Ben Zayed Institute for Personalized Cancer Therapy (to F. Janku), the ECD Global Alliance Grant (to F. Janku, E.L. Diamond, O. Abdel-Wahab), the Joan and Irwin Jacobs Fund (to R. Kurzrock), the National Institutes of Health through MD Anderson Cancer Center, Memorial Sloan Kettering Cancer Center, and Moores Cancer Center Support Grants [P30 CA016672 (to P.W.T. Pisters), P30 CA008748 (to C.B. Thompson), P30 CA023100 (to S.M. Lippman)].
Publisher Copyright:
© 2019 American Association for Cancer Research.
PY - 2019
Y1 - 2019
N2 - 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 ¼ 35; Rosai–Dorfman disease (RDD), n ¼ 3; mixed ECD/RDD, n ¼ 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.
AB - 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 ¼ 35; Rosai–Dorfman disease (RDD), n ¼ 3; mixed ECD/RDD, n ¼ 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.
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U2 - 10.1158/1535-7163.MCT-18-1244
DO - 10.1158/1535-7163.MCT-18-1244
M3 - Article
C2 - 31015311
AN - SCOPUS:85067217817
SN - 1535-7163
VL - 18
SP - 1149
EP - 1157
JO - Molecular cancer therapeutics
JF - Molecular cancer therapeutics
IS - 6
ER -