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A family harboring a germ‐line N‐terminal C/EBPα mutation and development of acute myeloid leukemia with an additional somatic C‐terminal C/EBPα mutation
Author(s) -
Nanri Tomoko,
Uike Naokuni,
Kawakita Toshiro,
Iwanaga Eisaku,
Mitsuya Hiroaki,
Asou Norio
Publication year - 2010
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20734
Subject(s) - cebpa , myeloid leukemia , mutation , biology , frameshift mutation , genetics , myeloid , terminal (telecommunication) , cancer research , microbiology and biotechnology , gene , telecommunications , computer science
C/EBPα plays an essential role as a transcription factor in myeloid cell differentiation. Here, we describe a Japanese family in which two individuals with acute myeloid leukemia (AML) and one healthy individual had an identical 4‐base pair insertion in the N‐terminal region of CEBPA (350_351insCTAC), resulting in the termination at codon 107 (I68fsX107). The father and a son at diagnosis of AML had different in‐frame insertion mutations in the C‐terminal region of C/EBPα. These C‐terminal mutations disappeared upon remission in both patients. Interestingly, the father showed different in‐frame insertion mutations in the C‐terminal CEBPA at the time of diagnosis and relapse. These data strongly suggest that the N‐terminal C/EBPα mutation predisposes to the occurrence of a C‐terminal C/EBPα mutation as a secondary genetic hit, causing AML. © 2009 Wiley‐Liss, Inc.