| Autor: |
Emile, Jean-François, Diamond, Eli L., Hélias-Rodzewicz, Zofia, Cohen-Aubart, Fleur, Charlotte, Frédéric, Hyman, David M., Kim, Eunhee, Rampal, Raajit, Patel, Minal, Ganzel, Chezi, Aumann, Shlomzion, Faucher, Gladwys, Le Gall, Catherine, Leroy, Karen, Colombat, Magali, Kahn, Jean-Emmanuel, Trad, Salim, Nizard, Philippe, Donadieu, Jean, Taly, Valérie, Amoura, Zahir, Abdel-Wahab, Omar, Haroche, Julien |
| Zdroj: |
Blood; November 2014, Vol. 124 Issue: 19 p3016-3019, 4p |
| Abstrakt: |
Erdheim-Chester disease (ECD) is a rare histiocytic disorder that is challenging to diagnose and treat. We performed molecular analysis of BRAFin the largest cohort of ECD patients studied to date followed by N/KRAS, PIK3CA, and AKT1mutational analysis in BRAFwild-type patients. Forty-six of 80 (57.5%) of patients were BRAFV600E-mutant. NRASmutations were detected in 3 of 17 ECD BRAFV600E wild-type patients. PIK3CAmutations (p.E542K, p.E545K, p.A1046T, and p.H1047R) were detected in 7 of 55 patients, 4 of whom also had BRAFmutations. Mutant NRASwas 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 NRASor PIK3CAmutations. |
| Databáze: |
Supplemental Index |
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