title: Mutational Analysis of Extranodal NK/T-Cell Lymphoma Using Targeted Sequencing with a Comprehensive Cancer Panel.
abstract: Extranodal natural killer (NK)/T-cell lymphoma, nasal type (NKTCL), is a malignant disorder of cytotoxic lymphocytes of NK or T cells. It is an aggressive neoplasm with a very poor prognosis. Although extranodal NKTCL reportedly has a strong association with Epstein-Barr virus, the molecular pathogenesis of NKTCL has been unexplored. The recent technological advancements in next-generation sequencing (NGS) have made DNA sequencing cost- and time-effective, with more reliable results. Using the Ion Proton Comprehensive Cancer Panel, we sequenced 409 cancer-related genes to identify somatic mutations in five NKTCL tissue samples. The sequencing analysis detected 25 mutations in 21 genes. Among them,KMT2D, a histone modification-related gene, was the most frequently mutated gene (four of the five cases). This result was consistent with recent NGS studies that have suggestedKMT2Das a novel driver gene in NKTCL. Mutations were also found inARID1A, a chromatin remodeling gene, andTP53, which also recurred in recent NGS studies. We also found mutations in 18 novel candidate genes, with molecular functions that were potentially implicated in cancer development. We suggest that these genes may result in multiple oncogenic events and may be used as potential bio-markers of NKTCL in the future.
authors.affiliation: Department of Pathology, Dankook University College of Medicine, Cheonan 31116, Korea.
authors.forename: Seungkyu
authors.initials: S
authors.lastname: Choi
authors.affiliation: Department of Pathology, Dankook University College of Medicine, Cheonan 31116, Korea.
authors.forename: Jai Hyang
authors.initials: JH
authors.lastname: Go
authors.affiliation: Department of Pathology, Eulji Medical Center, Eulji University School of Medicine, Seoul 01830, Korea.
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Kim
authors.affiliation: Department of Pathology, Eulji Medical Center, Eulji University School of Medicine, Seoul 01830, Korea.
authors.forename: Hojung
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Pathology, Eulji Medical Center, Eulji University School of Medicine, Seoul 01830, Korea.
authors.forename: Won Mi
authors.initials: WM
authors.lastname: Lee
authors.affiliation: Department of Neurosurgery, Dankook University College of Medicine, Cheonan 31116, Korea.
authors.forename: Chun-Sung
authors.initials: CS
authors.lastname: Cho
authors.affiliation: Department of Nanobiomedical Science, BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 31116, Korea.
authors.forename: Kyudong
authors.initials: K
authors.lastname: Han
keywords: ARID1A; KMT2D; TP53; deep sequencing; high-throughput DNA sequencing