Frequent BCOR aberrations in extranodal NK/T-Cell lymphoma, nasal type
Akito Dobashi
Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, Koto, Tokyo
Search for more papers by this authorNaoko Tsuyama
Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Koto, Tokyo
Search for more papers by this authorReimi Asaka
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
Search for more papers by this authorYuki Togashi
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
Search for more papers by this authorKyoko Ueda
Hematology and Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto, Tokyo
Search for more papers by this authorSeiji Sakata
Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, Koto, Tokyo
Search for more papers by this authorSatoko Baba
Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, Koto, Tokyo
Search for more papers by this authorKana Sakamoto
Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, Koto, Tokyo
Search for more papers by this authorKiyohiko Hatake
Hematology and Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto, Tokyo
Search for more papers by this authorCorresponding Author
Kengo Takeuchi
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
Correspondence to: Kengo Takeuchi; Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo 135-8550, Japan. E-mail: [email protected]Search for more papers by this authorAkito Dobashi
Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, Koto, Tokyo
Search for more papers by this authorNaoko Tsuyama
Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Koto, Tokyo
Search for more papers by this authorReimi Asaka
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
Search for more papers by this authorYuki Togashi
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
Search for more papers by this authorKyoko Ueda
Hematology and Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto, Tokyo
Search for more papers by this authorSeiji Sakata
Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, Koto, Tokyo
Search for more papers by this authorSatoko Baba
Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, Koto, Tokyo
Search for more papers by this authorKana Sakamoto
Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, Koto, Tokyo
Search for more papers by this authorKiyohiko Hatake
Hematology and Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto, Tokyo
Search for more papers by this authorCorresponding Author
Kengo Takeuchi
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
Correspondence to: Kengo Takeuchi; Pathology Project for Molecular Targets, The Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo 135-8550, Japan. E-mail: [email protected]Search for more papers by this authorAbstract
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. © 2016 Wiley Periodicals, Inc.
Supporting Information
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