Recurrent RAS and PIK3CA mutations in Erdheim-Chester disease

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 wild-type patients. Forty-six of 80 (57.5%) of patients were BRAFV600E-mutant. NRAS mutations were detected in 3 of 17 ECD BRAFV600E wild-type patients. PIK3CA mutations (p.E542K, p.E545K, p.A1046T, and p.H1047R) were detected in 7 of 55 patients, 4 of whom 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 signaling in ECD. These results provide a rationale for targeting mutant RAS or PI3K/AKT/mTOR signaling in the subset of ECD patients with NRAS or PIK3CA mutations.
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J.-F. Emile, E. Diamond, Z. Helias-Rodzewicz, F. Cohen-Aubart, F. Charlotte, et al.. Recurrent RAS and PIK3CA mutations in Erdheim-Chester disease. Blood, American Society of Hematology, 2014, 124 (19), pp.3016-3019. ⟨10.1182/blood-2014-04-570937⟩. ⟨inserm-02299579⟩

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