Format

Send to

Choose Destination
Nat Genet. 2015 Nov;47(11):1304-15. doi: 10.1038/ng.3415. Epub 2015 Oct 5.

Integrated molecular analysis of adult T cell leukemia/lymphoma.

Author information

1
Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
2
Department of Gastroenterology and Hematology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
3
Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
4
Division of Systems Biology, Center for Neurological Disease and Cancer, Graduate School of Medicine, Nagoya University, Nagoya, Japan.
5
Laboratory of Virus Control, Institute for Virus Research, Kyoto University, Kyoto, Japan.
6
Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan.
7
Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.
8
Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan.
9
Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.
10
Department of Advanced Diagnosis, Clinical Research Center, Nagoya Medical Center, Nagoya, Japan.
11
Department of Frontier Life Science, Nagasaki University Graduate School of Biomedical Science, Nagasaki, Japan.
12
Department of Hematology, Kumamoto University School of Medicine, Kumamoto, Japan.
13
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
14
Department of Hematology, Sasebo City General Hospital, Sasebo, Japan.
15
Department of Hematology, Atomic Bomb Disease and Hibakusya Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan.
16
Department of Hematology, National Cancer Center Hospital, Tokyo, Japan.
17
KAN Research Institute, Inc., Kobe, Japan.
18
Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
19
Division of Hematology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan.
20
Department of Hematology and Oncology, Kanazawa University Hospital, Kanazawa, Japan.
21
Division of Hematology, Department of Internal Medicine, Tokyo Metropolitan Ohtsuka Hospital, Tokyo, Japan.
22
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
23
Pathology Project for Molecular Targets, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
24
Laboratory of Molecular Medicine, Human Genome Center, The institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Abstract

Adult T cell leukemia/lymphoma (ATL) is a peripheral T cell neoplasm of largely unknown genetic basis, associated with human T cell leukemia virus type-1 (HTLV-1) infection. Here we describe an integrated molecular study in which we performed whole-genome, exome, transcriptome and targeted resequencing, as well as array-based copy number and methylation analyses, in a total of 426 ATL cases. The identified alterations overlap significantly with the HTLV-1 Tax interactome and are highly enriched for T cell receptor-NF-κB signaling, T cell trafficking and other T cell-related pathways as well as immunosurveillance. Other notable features include a predominance of activating mutations (in PLCG1, PRKCB, CARD11, VAV1, IRF4, FYN, CCR4 and CCR7) and gene fusions (CTLA4-CD28 and ICOS-CD28). We also discovered frequent intragenic deletions involving IKZF2, CARD11 and TP73 and mutations in GATA3, HNRNPA2B1, GPR183, CSNK2A1, CSNK2B and CSNK1A1. Our findings not only provide unique insights into key molecules in T cell signaling but will also guide the development of new diagnostics and therapeutics in this intractable tumor.

PMID:
26437031
DOI:
10.1038/ng.3415
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center