title: Somatic mosaicism for oncogenic NRAS mutations in juvenile myelomonocytic leukemia.
abstract: Juvenile myelomonocytic leukemia (JMML) is a rare pediatric myeloid neoplasm characterized by excessive proliferation of myelomonocytic cells. Somatic mutations in genes involved in GM-CSF signal transduction, such as NRAS, KRAS, PTPN11, NF1, and CBL, have been identified in more than 70% of children with JMML. In the present study, we report 2 patients with somatic mosaicism for oncogenic NRAS mutations (G12D and G12S) associated with the development of JMML. The mutated allele frequencies quantified by pyrosequencing were various and ranged from 3%-50% in BM and other somatic cells (ie, buccal smear cells, hair bulbs, or nails). Both patients experienced spontaneous improvement of clinical symptoms and leukocytosis due to JMML without hematopoietic stem cell transplantation. These patients are the first reported to have somatic mosaicism for oncogenic NRAS mutations. The clinical course of these patients suggests that NRAS mosaicism may be associated with a mild disease phenotype in JMML.
authors: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Sayoko
authors: S
authors: Doisaki
authors: Hideki
authors: H
authors: Muramatsu
authors: Akira
authors: A
authors: Shimada
authors: Yoshiyuki
authors: Y
authors: Takahashi
authors: Makiko
authors: M
authors: Mori-Ezaki
authors: Masanori
authors: M
authors: Sato
authors: Hiroyuki
authors: H
authors: Kawaguchi
authors: Akitoshi
authors: A
authors: Kinoshita
authors: Manabu
authors: M
authors: Sotomatsu
authors: Yasuhide
authors: Y
authors: Hayashi
authors: Yoko
authors: Y
authors: Furukawa-Hibi
authors: Kiyofumi
authors: K
authors: Yamada
authors: Hideaki
authors: H
authors: Hoshino
authors: Hitoshi
authors: H
authors: Kiyoi
authors: Nao
authors: N
authors: Yoshida
authors: Hirotoshi
authors: H
authors: Sakaguchi
authors: Atsushi
authors: A
authors: Narita
authors: Xinan
authors: X
authors: Wang
authors: Olfat
authors: O
authors: Ismael
authors: Yinyan
authors: Y
authors: Xu
authors: Nobuhiro
authors: N
authors: Nishio
authors: Makito
authors: M
authors: Tanaka
authors: Asahito
authors: A
authors: Hama
authors: Kenichi
authors: K
authors: Koike
authors: Seiji
authors: S
authors: Kojima
mesh_terms: D001483:Base Sequence; D002648:Child; D004252:DNA Mutational Analysis; D006801:Humans; D007223:Infant; D054429:Leukemia, Myelomonocytic, Juvenile / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009030:Mosaicism; D009154:Mutation / Q000235:genetics*; D009857:Oncogenes / Q000235:genetics*; D018631:ras Proteins / Q000235:genetics*
chemical_list: D018631:ras Proteins