Recurrent RAS and PIK3CA mutations in Erdheim-Chester disease Journal Article
| Authors: | Emile, J. F.; Diamond, E. L.; Hélias-Rodzewicz, Z.; Cohen-Aubart, F.; Charlotte, F.; Hyman, D. M.; Kim, E.; Rampal, R.; Patel, M.; Ganzel, C.; Aumann, S.; Faucher, G.; Gall, C. L.; Leroy, K.; Colombat, M.; Kahn, J. E.; Trad, S.; Nizard, P.; Donadieu, J.; Taly, V.; Amoura, Z.; Abdel-Wahab, O.; Haroche, J. |
| Article Title: | 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 of55 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. |
| Keywords: | immunohistochemistry; signal transduction; protein kinase b; protein expression; gene mutation; human cell; major clinical study; mutational analysis; mammalian target of rapamycin; ras protein; real time polymerase chain reaction; histiocyte; cd3+ t lymphocyte; b raf kinase; genomic dna; peripheral blood mononuclear cell; pyrosequencing; lymphoid cell; phosphatidylinositol 4,5 bisphosphate 3 kinase; human; article; erdheim chester disease |
| Journal Title: | Blood |
| Volume: | 124 |
| Issue: | 19 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2014-11-06 |
| Start Page: | 3016 |
| End Page: | 3019 |
| Language: | English |
| DOI: | 10.1182/blood-2014-04-570937 |
| PROVIDER: | scopus |
| PMCID: | PMC4224196 |
| PUBMED: | 25150293 |
| DOI/URL: | |
| Notes: | Export Date: 1 December 2014 -- Source: Scopus |
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