title: Genetic alterations of JAK/STAT cascade and histone modification in extranodal NK/T-cell lymphoma nasal type.
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.
authors.affiliation: Genomic Medicine Institute (GMI), Medical Research Center, Seoul National University, Seoul, Korea.
authors.forename: Seungbok
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea.
authors.forename: Ha Young
authors.initials: HY
authors.lastname: Park
authors.affiliation: Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: So Young
authors.initials: SY
authors.lastname: Kang
authors.affiliation: Division of Hematology-Oncology, Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Seok Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea.
authors.forename: Jinha
authors.initials: J
authors.lastname: Hwang
authors.affiliation: Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Seungho
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Soo Heon
authors.initials: SH
authors.lastname: Kwak
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.|Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology and College of Medicine, Seoul National University, Seoul, Korea.
authors.forename: Kyong Soo
authors.initials: KS
authors.lastname: Park
authors.affiliation: Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Hae Yong
authors.initials: HY
authors.lastname: Yoo
authors.affiliation: Division of Hematology-Oncology, Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Won Seog
authors.initials: WS
authors.lastname: Kim
authors.affiliation: Genomic Medicine Institute (GMI), Medical Research Center, Seoul National University, Seoul, Korea.|Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea.|Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jong-Il
authors.initials: JI
authors.lastname: Kim
authors.affiliation: Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Young Hyeh
authors.initials: YH
authors.lastname: Ko
mesh_terms: D004252:DNA Mutational Analysis; D020869:Gene Expression Profiling; D059014:High-Throughput Nucleotide Sequencing; D006657:Histones / Q000235:genetics*; D006801:Humans; D053612:Janus Kinases / Q000235:genetics*; D054391:Lymphoma, Extranodal NK-T-Cell / Q000235:genetics*; D050791:STAT Transcription Factors / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D006657:Histones; D050791:STAT Transcription Factors; D053612:Janus Kinases
keywords: JAK-STAT pathway; chromatin modification; extranodal NK/T-cell lymphoma nasal type; next-generation sequencing; somatic mutation