Format

Send to

Choose Destination
Nat Genet. 2014 Feb;46(2):171-5. doi: 10.1038/ng.2872. Epub 2014 Jan 12.

Somatic RHOA mutation in angioimmunoblastic T cell lymphoma.

Author information

1
1] Department of Hematology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan. [2].
2
1] Cancer Genomics Project, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. [2] Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. [3].
3
Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
4
Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Tokyo, Japan.
5
Department of Hematology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
6
Division of Pathology, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
7
1] Cancer Genomics Project, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. [2] Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
8
Cancer Genomics Project, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
9
Pathology Project for Molecular Targets, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
10
1] Department of Hematology, Toranomon Hospital, Tokyo, Japan. [2] Okinaka Memorial Institute for Medical Research, Tokyo, Japan.
11
Department of Pathology, Toranomon Hospital, Tokyo, Japan.
12
Department of Dermatology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
13
Department of Hematology, Tsuchiura Kyodo General Hospital, Tsuchiura, Japan.
14
Department of Hematology, Mito Medical Center, National Hospital Organization, Mito, Japan.
15
Department of Hematology, Tsukuba Memorial Hospital, Tsukuba, Japan.
16
Department of Hematology, JA Toride Medical Center, Toride, Japan.
17
Department of Pathology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
18
Department of Medical Genetics, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
19
Laboratory of Sequence Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
20
1] Department of Hematology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan. [2] Department of Clinical Laboratory, University of Tsukuba Hospital, Tsukuba, Japan.
21
Department of Clinical Laboratory, University of Tsukuba Hospital, Tsukuba, Japan.
22
1] Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan. [2] Laboratory of Sequence Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
23
Department of Pathology, Tokai University School of Medicine, Isehara, Japan.
24
1] Division of Pathology, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan. [2] Pathology Project for Molecular Targets, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
25
1] Department of Hematology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan. [2] Life Science Center, Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba, Japan. [3].

Abstract

Angioimmunoblastic T cell lymphoma (AITL) is a distinct subtype of peripheral T cell lymphoma characterized by generalized lymphadenopathy and frequent autoimmune-like manifestations. Although frequent mutations in TET2, IDH2 and DNMT3A, which are common to various hematologic malignancies, have been identified in AITL, the molecular pathogenesis specific to this lymphoma subtype is unknown. Here we report somatic RHOA mutations encoding a p.Gly17Val alteration in 68% of AITL samples. Remarkably, all cases with the mutation encoding p.Gly17Val also had TET2 mutations. The RHOA mutation encoding p.Gly17Val was specifically identified in tumor cells, whereas TET2 mutations were found in both tumor cells and non-tumor hematopoietic cells. RHOA encodes a small GTPase that regulates diverse biological processes. We demonstrated that the Gly17Val RHOA mutant did not bind GTP and also inhibited wild-type RHOA function. Our findings suggest that impaired RHOA function in cooperation with preceding loss of TET2 function contributes to AITL-specific pathogenesis.

PMID:
24413737
DOI:
10.1038/ng.2872
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center