@article{db2380a9cc294c299257d1b997e1a430,
title = "Recurrent CDC25C mutations drive malignant transformation in FPD/AML",
abstract = "Familial platelet disorder (FPD) with predisposition to acute myelogenous leukaemia (AML) is characterized by platelet defects with a propensity for the development of haematological malignancies. Its molecular pathogenesis is poorly understood, except for the role of germline RUNX1 mutations. Here we show that CDC25C mutations are frequently found in FPD/AML patients (53%). Mutated CDC25C disrupts the G2/M checkpoint and promotes cell cycle progression even in the presence of DNA damage, suggesting a critical role for CDC25C in malignant transformation in FPD/AML. The predicted hierarchical architecture shows that CDC25C mutations define a founding pre-leukaemic clone, followed by stepwise acquisition of subclonal mutations that contribute to leukaemia progression. In three of seven individuals with CDC25C mutations, GATA2 is the target of subsequent mutation. Thus, CDC25C is a novel gene target identified in haematological malignancies. CDC25C is also useful as a clinical biomarker that predicts progression of FPD/AML in the early stage.",
author = "Akihide Yoshimi and Takashi Toya and Masahito Kawazu and Toshihide Ueno and Ayato Tsukamoto and Hiromitsu Iizuka and Masahiro Nakagawa and Yasuhito Nannya and Shunya Arai and Hironori Harada and Kensuke Usuki and Yasuhide Hayashi and Etsuro Ito and Keita Kirito and Hideaki Nakajima and Motoshi Ichikawa and Hiroyuki Mano and Mineo Kurokawa",
note = "Funding Information: This work was supported in part by grants-in-aid from the Ministry of Health, Labor and Welfare of Japan (H23-Nanchi-Ippan-104; M. Kurokawa) and KAKENHI (24659457; M. Kurokawa). We thank R. Lewis (University of Nebraska Medical Center) and T. Kitamura (Institute of Medical Science, The University of Tokyo) for providing essential materials; T. Koike (Nagaoka Red Cross Hospital), K. Nara (Ootemachi Hospital), K. Suzuki (Japanese Red Cross Medical Center), H. Harada (Fujigaoka Hospital), Y. Morita (Kinki University), M. Matsuda (PL Hospital), H. Kashiwagi (Osaka University), T. Kiguchi (Chugoku Central Hospital), T. Masunari (Chugoku Central Hospital), K. Yamamoto (Yokohama City Minato Red Cross Hospital), T. Takahashi (Mitsui Memorial Hospital) and T. Takaku (Juntendo University) for providing patient samples; M. Kuramitsu (National Institutte of Infectious Diseases) for providing kind support of synchronized quantitative PCR; and K. Tanaka and Y. Shimamura for their technical assistance.",
year = "2014",
month = aug,
day = "27",
doi = "10.1038/ncomms5770",
language = "English",
volume = "5",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}