Oncotarget

Research Papers:

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

Seungbok Lee _, Ha Young Park, So Young Kang, Seok Jin Kim, Jinha Hwang, Seungho Lee, Soo Heon Kwak, Kyong Soo Park, Hae Yong Yoo, Won Seog Kim, Jong-Il Kim and Young Hyeh Ko

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Oncotarget. 2015; 6:17764-17776. https://doi.org/10.18632/oncotarget.3776

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Abstract

Seungbok Lee1,*, Ha Young Park2,*, So Young Kang3, Seok Jin Kim4, Jinha Hwang2, Seungho Lee7, Soo Heon Kwak5, Kyong Soo Park5,6, Hae Yong Yoo7, Won Seog Kim4,*, Jong-Il Kim1,2,8,*, Young Hyeh Ko3,*

1Genomic Medicine Institute (GMI), Medical Research Center, Seoul National University, Seoul, Korea

2Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea

3Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

4Division of Hematology-Oncology, Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

5Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea

6Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology and College of Medicine, Seoul National University, Seoul, Korea

7Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University School of Medicine, Seoul, Korea

8Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, Korea

*These authors have contributed equally to this work

Correspondence to:

Young Hyeh Ko, e-mail: yhko310@skku.edu

Jong-Il Kim, e-mail: jongil@snu.ac.kr

Won Seog Kim, e-mail: wskimsmc@skku.edu

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

Received: November 24, 2014     Accepted: April 13, 2015     Published: April 25, 2015

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.


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