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American Society of Hematology, Blood, 19(124), p. 3016-3019, 2014

DOI: 10.1182/blood-2014-04-570937

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Recurrent RAS and PIK3CA mutations in Erdheim-Chester disease

Journal article published in 2014 by Jean-François Emile, Eli L. Diamond, Zofia Hélias-Rodzewicz, Z. Helias-Rodzewicz, Fleur Cohen-Aubart, Frédéric Charlotte, David M. Hyman, Eunhee Kim, Raajit Rampal, Minal Patel, Chezi Ganzel, Shlomzion Aumann, Gladwys Faucher, Catherine Le Gall, Catherine Le Gall and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Erdheim-Chester Disease (ECD) is a rare histiocytic disorder that is challenging to diagnose and treat. We performed molecular analysis of BRAF in the largest cohort of ECD patients studied to date followed by N/KRAS, PIK3CA, and AKT1 mutational analysis in BRAF wildtype patients. 57.5% (46/80) of patients were BRAFV600E mutant. NRAS mutations were detected in 3/17 ECD BRAFV600E wildtype patients. PIK3CA mutations (p.E542K, p.E545K, p.A1046T and p.H1047R) were detected in 7/55 patients, of whom 4 also had BRAF mutations. Mutant NRAS was present in peripheral blood CD14+ cells, but not lymphoid cells, from an NRASQ61R mutant patient. Our results underscore the central role of RAS-RAF-MEK-ERK activation in ECD and identify an important role of activation of RAS-PI3K-AKT signalling in ECD. These results provide a rationale for targeting mutant RAS or PI3K/AKT/mTOR signalling in the subset of ECD patients with NRAS or PIK3CA mutations.