title: Frequent BCOR aberrations in extranodal NK/T-Cell lymphoma, nasal type.
abstract: Extranodal natural killer/T cell lymphoma (ENKTL) is a rare subtype of lymphoma. Recurrent mutations in the JAK-STAT pathway, recently reported in ENKTL cases, are interesting in terms of both pathogenesis and inhibitor therapy. However, the frequencies of these mutations are low and variable among reports, and other pathognomonic mutations in ENKTL remain to be elucidated. In the present study, targeted capture sequencing of 602 cancer-related genes from 25 frozen ENKTL samples was performed, 11 of which were matched to normal samples. Several recurrent somatic mutations involving BCOR (32%), TP53 (16%), DDX3X (12%), FAT4 (8%), NRAS (8%), MLL3 (12%), and MIR17HG (8%) were identified. The pattern of BCOR aberrations (1 nonsense and 5 frame-shift mutations, a mutation leading to a splicing error, and gene loss) suggested that loss of function of BCOR was the functionally important outcome of such changes. The literature was reviewed and the public data on BCOR aberrations was reanalyzed and it was found that the aberrations were frequently found in myeloid neoplasms, but, interestingly, were highly specific to ENKTL among lymphoid malignancies. Given the high frequency and pattern of aberration, BCOR is likely to play an important role in ENKTL pathogenesis as a tumor suppressor gene.
authors.affiliation: Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, Koto, Tokyo.
authors.forename: Akito
authors.initials: A
authors.lastname: Dobashi
authors.affiliation: Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Koto, Tokyo.
authors.forename: Naoko
authors.initials: N
authors.lastname: Tsuyama
authors.affiliation: Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, Koto, Tokyo.|Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Koto, Tokyo.
authors.forename: Reimi
authors.initials: R
authors.lastname: Asaka
authors.affiliation: Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, Koto, Tokyo.|Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Koto, Tokyo.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Togashi
authors.affiliation: Hematology and Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto, Tokyo.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Ueda
authors.affiliation: Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, Koto, Tokyo.
authors.forename: Seiji
authors.initials: S
authors.lastname: Sakata
authors.affiliation: Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, Koto, Tokyo.
authors.forename: Satoko
authors.initials: S
authors.lastname: Baba
authors.affiliation: Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, Koto, Tokyo.
authors.forename: Kana
authors.initials: K
authors.lastname: Sakamoto
authors.affiliation: Hematology and Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto, Tokyo.
authors.forename: Kiyohiko
authors.initials: K
authors.lastname: Hatake
authors.affiliation: Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, Koto, Tokyo.|Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Koto, Tokyo.
authors.forename: Kengo
authors.initials: K
authors.lastname: Takeuchi
mesh_terms: D056915:DNA Copy Number Variations; D006801:Humans; D054391:Lymphoma, Extranodal NK-T-Cell / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012326:RNA Splicing; D012097:Repressor Proteins / Q000235:genetics*
chemical_list: C411984:BCOR protein, human; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins