Recurrent RAS and PIK3CA mutations in Erdheim-Chester disease.

[erdheim-chester disease]

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 , PIK 3 CA , and AKT 1 mutational analysis in BRAF wild-type patients . Forty -six of 80 (57 .5 %) of patients were BRAFV 600 E -mutant . NRAS mutations were detected in 3 of 17 ECD BRAFV 600 E wild-type patients . PIK 3 CA mutations (p .E 542 K , p .E 545 K , p .A 1046 T , and p .H 1047 R ) were detected in 7 of 55 patients , 4 of whom also had BRAF mutations . Mutant NRAS was present in peripheral blood CD 14 (+) cells , but not lymphoid cells , from an NRASQ 61 R 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-PI 3 K -AKT signaling in ECD . These results provide a rationale for targeting mutant RAS or PI 3 K /AKT /mTOR signaling in the subset of ECD patients with NRAS or PIK 3 CA mutations .

Diseases
Validation

Diseases presenting "central role" symptom

erdheim-chester disease

gm1 gangliosidosis

inclusion body myositis

kabuki syndrome

locked-in syndrome

primary effusion lymphoma

severe combined immunodeficiency

von hippel-lindau disease

wiskott-aldrich syndrome

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