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Oncotarget. 2015 Jul 10;6(19):17764-76.

Genetic alterations of JAK/STAT cascade and histone modification in extranodal NK/T-cell lymphoma nasal type.

Author information

1
Genomic Medicine Institute (GMI), Medical Research Center, Seoul National University, Seoul, Korea.
2
Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea.
3
Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
4
Division of Hematology-Oncology, Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
5
Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University School of Medicine, Seoul, Korea.
6
Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
7
Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology and College of Medicine, Seoul National University, Seoul, Korea.
8
Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, Korea.

Abstract

Extranodal NK/T-cell lymphoma nasal type (ENKL) is a rare type of non-Hodgkin lymphoma that more frequently occurs in East Asia and Latin America. Even though its molecular background has been discussed in the last few years, the current knowledge does not explain the disease pathogenesis in most cases of ENKL. Here, we performed multiple types of next-generation sequencing on 34 ENKL samples, including whole-exome sequencing (9 cancer tissues and 4 cancer cell lines), targeted sequencing (21 cancer tissues), and RNA sequencing (3 cancer tissues and 4 cancer cell lines). Mutations were found most frequently in 3 genes, STAT3, BCOR, and MLL2 (which were present in 9, 7, and 6 cancer samples, respectively), whereas there were only 2 cases of JAK3 mutation. In total, JAK/STAT pathway- and histone modification-related genes accounted for 55.9% and 38.2% of cancer samples, respectively, and their involvement in ENKL pathogenesis was also supported by gene expression analysis. In addition, we provided 177 genes upregulated only in cancer tissues, which appear to be linked with angiocentric and angiodestructive growth of ENKL. In this study, we propose several novel driver genes of ENKL, and show that these genes and their functional groups may be future therapeutic targets of this disease.

KEYWORDS:

JAK-STAT pathway; chromatin modification; extranodal NK/T-cell lymphoma nasal type; next-generation sequencing; somatic mutation

PMID:
25980440
PMCID:
PMC4627344
DOI:
10.18632/oncotarget.3776
[Indexed for MEDLINE]
Free PMC Article

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