Recurrent RAS and PIK3CA mutations in Erdheim-Chester disease

被引：186

作者：

Emile, Jean-Francois ^{[1
,2
]}

Diamond, Eli L. ^{[3
]}

Helias-Rodzewicz, Zofia ^{[1
,2
]}

Cohen-Aubart, Fleur ^{[4
,5
,6
]}

Charlotte, Frederic ^{[6
,7
]}

Hyman, David M. ^{[8
]}

Kim, Eunhee ^{[9
,10
]}

Rampal, Raajit ^{[9
,10
]}

Patel, Minal ^{[9
,10
]}

Ganzel, Chezi ^{[11
]}

Aumann, Shlomzion ^{[9
,10
]}

Faucher, Gladwys ^{[1
,2
]}

Le Gall, Catherine ^{[1
,2
]}

Leroy, Karen ^{[12
,13
]}

Colombat, Magali ^{[14
]}

Kahn, Jean-Emmanuel ^{[15
]}

Trad, Salim ^{[16
]}

Nizard, Philippe ^{[17
]}

Donadieu, Jean ^{[1
,18
,19
]}

Taly, Valerie ^{[17
]}

Amoura, Zahir ^{[4
,5
,6
]}

Abdel-Wahab, Omar ^{[9
,10
]}

Haroche, Julien ^{[4
,5
,6
]}

机构：

[1] Univ Versailles, Unite Rech EA 4340, Boulogne, France

[2] Hop Ambroise Pare, AP HP, Dept Pathol, F-92104 Boulogne, France

[3] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10065 USA

[4] Hop La Pitie Salpetriere, AP HP, Dept Internal Med, Paris, France

[5] Hop La Pitie Salpetriere, AP HP, French Reference Ctr Rare Autoimmune & Syst Dis, Paris, France

[6] Univ Paris 06, Paris, France

[7] Hop La Pitie Salpetriere, AP HP, Dept Pathol, Paris, France

[8] Mem Sloan Kettering Canc Ctr, Expt Therapeut Unit, New York, NY 10065 USA

[9] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA

[10] Mem Sloan Kettering Canc Ctr, Leukemia Serv, New York, NY 10065 USA

[11] Shaare Zedek Med Ctr, Dept Hematol, Jerusalem, Israel

[12] Univ Paris Est Creteil, Creteil, France

[13] Hosp Henri Mondor, AP HP, Dept Pathol, Creteil, France

[14] Foch Hosp, Dept Pathol, Suresne, France

[15] Foch Hosp, Dept Internal Med, Suresne, France

[16] Hop Ambroise Pare, AP HP, Dept Internal Med, F-92104 Boulogne, France

[17] Univ Paris Sorbonne Cite, INSERM, Paris, France

[18] Trousseau Hosp, AP HP, Dept Pediat, Paris, France

[19] Trousseau Hosp, AP HP, French Reference Ctr Langerhans Cell Histiocytosi, Paris, France

来源：

BLOOD | 2014年 / 124卷 / 19期

关键词：

LANGERHANS CELL HISTIOCYTOSIS; BRAF MUTATIONS; MEK INHIBITION; NRAS; EFFICACY; MELANOMA;

D O I：

10.1182/blood-2014-04-570937

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：3016 / 3019

页数：4

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