{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:20:36Z","timestamp":1767918036412,"version":"3.49.0"},"reference-count":46,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,23]],"date-time":"2020-06-23T00:00:00Z","timestamp":1592870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Seoul National University (SNU) Invitation Program for Distinguished Scholar","award":["0320170160 [2017-1312]"],"award-info":[{"award-number":["0320170160 [2017-1312]"]}]},{"DOI":"10.13039\/501100004085","name":"Ministry of Education, Science and Technology","doi-asserted-by":"publisher","award":["NRF-2016R1D1A1B01015964"],"award-info":[{"award-number":["NRF-2016R1D1A1B01015964"]}],"id":[{"id":"10.13039\/501100004085","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004085","name":"Ministry of Education, Science and Technology","doi-asserted-by":"publisher","award":["NRF-2019R1F1A1061920"],"award-info":[{"award-number":["NRF-2019R1F1A1061920"]}],"id":[{"id":"10.13039\/501100004085","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Nodal marginal zone lymphoma (NMZL) is a rare B-cell neoplasm, the genetic and transcriptomic landscape of which are unclear. Using high-throughput sequencing for whole-exome and transcriptome, we investigated the genetic characteristics of NMZL in a discovery cohort (n = 8) and validated their features in an extended cohort (n = 30). Novel mutations in NFKBIE and ITPR2 were found in 7.9% (3\/38) and 13.9% (5\/36), respectively, suggesting roles for the NF-\u03baB pathway and B-cell-receptor-mediated calcium signaling pathway in the pathogenesis of NMZL. RNA-seq showed that NMZLs were characterized by an aberrant marginal zone differentiation, associated with an altered IRF4-NOTCH2 axis and the enrichment of various oncogenic pathways. Based on gene expression profile, two subgroups were identified. Compared with subgroup 1, subgroup 2 showed the following: the significant enrichment of cell cycle-associated and MYC-signaling pathways, a more diverse repertoire of upstream regulators, and higher Ki-67 proliferation indices. We designated two subgroups according to Ki-67 labeling, and subgroup 2 was significantly associated with a shorter progression-free survival (p = 0.014), a greater proportion of large cells (p = 0.009), and higher MYC expression (p = 0.026). We suggest that NMZL has unique features and, in this study, we provide information as to the heterogeneity of this enigmatic entity.<\/jats:p>","DOI":"10.3390\/cancers12061669","type":"journal-article","created":{"date-parts":[[2020,6,24]],"date-time":"2020-06-24T07:14:19Z","timestamp":1592982859000},"page":"1669","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Discovery of Novel Recurrent Mutations and Clinically Meaningful Subgroups in Nodal Marginal Zone Lymphoma"],"prefix":"10.3390","volume":"12","author":[{"given":"Jiwon","family":"Koh","sequence":"first","affiliation":[{"name":"Department of Pathology, Seoul National University Hospital, Seoul 03080, Korea"},{"name":"Department of Pathology, Seoul National University College of Medicine, Seoul 03080, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Insoon","family":"Jang","sequence":"additional","affiliation":[{"name":"Division of Clinical Bioinformatics, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9722-1800","authenticated-orcid":false,"given":"Seongmin","family":"Choi","sequence":"additional","affiliation":[{"name":"Division of Clinical Bioinformatics, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Korea"},{"name":"Seoul National University College of Medicine, Seoul 03080, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sehui","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pathology, Seoul National University Hospital, Seoul 03080, Korea"},{"name":"Department of Pathology, Seoul National University College of Medicine, Seoul 03080, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingeon","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Seoul National University College of Medicine, Seoul 03080, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyun Kyung","family":"Ahn","sequence":"additional","affiliation":[{"name":"Cancer Research Institute, Seoul National University, Seoul 03080, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheol","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pathology, Seoul National University Hospital, Seoul 03080, Korea"},{"name":"Department of Pathology, Seoul National University College of Medicine, Seoul 03080, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin Ho","family":"Paik","sequence":"additional","affiliation":[{"name":"Department of Pathology, Seoul National University Bundang Hospital, Seongnam-si 46371, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chul Woo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pathology, Seoul National University Hospital, Seoul 03080, Korea"},{"name":"Department of Pathology, Seoul National University College of Medicine, Seoul 03080, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megan S.","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4586-5062","authenticated-orcid":false,"given":"Kwangsoo","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Clinical Bioinformatics, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8466-9681","authenticated-orcid":false,"given":"Yoon Kyung","family":"Jeon","sequence":"additional","affiliation":[{"name":"Department of Pathology, Seoul National University Hospital, Seoul 03080, Korea"},{"name":"Department of Pathology, Seoul National University College of Medicine, Seoul 03080, Korea"},{"name":"Cancer Research Institute, Seoul National University, Seoul 03080, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"443","DOI":"10.3322\/caac.21357","article-title":"2016 US lymphoid malignancy statistics by World Health Organization subtypes","volume":"66","author":"Teras","year":"2016","journal-title":"CA A Cancer J. 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