1. The genetic landscape of dural marginal zone lymphomas
- Author
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Govind Bhagat, Odelia Nahum, Pallavi Khattar, Brynn Levy, Mahesh M. Mansukhani, Francesco Bertoni, Stefania Pittaluga, Karthik A. Ganapathi, Fabio M. Iwamoto, Daniela Hoehn, Jinli Chen, Vundavalli V. Murty, Yi Xie, Luciano Cascione, Preti Jain, Elaine S. Jaffe, Bachir Alobeid, and Vaidehi Jobanputra
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Adult ,Male ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,DNA Mutational Analysis ,Marginal zone lymphoma ,Columbia university ,Mutually exclusive events ,Loss of heterozygosity ,03 medical and health sciences ,Cytogenetics ,NOTCH2 ,0302 clinical medicine ,Genetic variation ,Meningeal Neoplasms ,Genetics ,Humans ,Medicine ,Genetic Predisposition to Disease ,dural marginal zone lymphoma ,genome ,In Situ Hybridization, Fluorescence ,TNFAIP3 ,Chromosome Aberrations ,business.industry ,Genetic Variation ,Lymphoma, B-Cell, Marginal Zone ,Middle Aged ,mutations ,Marginal zone ,Mutational analysis ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,FOS: Biological sciences ,Mutation ,Female ,Lymphomas ,Dura Mater ,business ,Hematopathology ,Research Paper - Abstract
// Karthik A. Ganapathi 1 , Vaidehi Jobanputra 1 , Fabio Iwamoto 2 , Preti Jain 1 , Jinli Chen 1 , Luciano Cascione 3 , Odelia Nahum 1 , Brynn Levy 1 , Yi Xie 4 , Pallavi Khattar 5 , Daniela Hoehn 1 , Francesco Bertoni 3 , Vundavalli V. Murty 1 , Stefania Pittaluga 4 , Elaine S. Jaffe 4 , Bachir Alobeid 1 , Mahesh M. Mansukhani 1,* and Govind Bhagat 1,* 1 Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA 2 Department of Neurology, Columbia University Medical Center, New York, NY, USA 3 Institute of Oncology Research and Oncology Institute of Southern Switzerland, Bellinzona, Switzerland 4 Hematopathology Section, Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA 5 Department of Pathology, New York Medical College, Valhalla, NY, USA * These authors have contributed equally to this work Correspondence to: Govind Bhagat, email: // Mahesh M. Mansukhani, email: // Keywords : dural marginal zone lymphoma, genome, mutations, TNFAIP3, NOTCH2 Received : April 21, 2016 Accepted : May 14, 2016 Published : May 27, 2016 Abstract The dura is a rare site of involvement by marginal zone lymphoma (MZL) and the biology of dural MZL is not well understood. We performed genome-wide DNA copy number and targeted mutational analysis of 14 dural MZL to determine the genetic landscape of this entity. Monoallelic and biallelic inactivation of TNFAIP3 by mutation (n=5) or loss (n=1) was observed in 6/9 (67%) dural MZL exhibiting plasmacytic differentiation, including 3 IgG4+ cases. In contrast, activating NOTCH2 mutations were detected in 4/5 (80%) dural MZL displaying variable monocytoid morphology. Inactivating TBL1XR1 mutations were identified in all NOTCH2 mutated cases. Recurrent mutations in KLHL6 (n=2) and MLL2 (n=2) were also detected. Gains at 6p25.3 (n=2) and losses at 1p36.32 (n=3) were common chromosomal imbalances, with loss of heterozygosity (LOH) of these loci observed in a subset of cases. Translocations involving the IGH or MALT1 genes were not identified. Our results indicate genetic similarities between dural MZL and other MZL subtypes. However, recurrent and mutually exclusive genetic alterations of TNFAIP3 and NOTCH2 appear to be associated with distinct disease phenotypes in dural MZL.
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- 2016
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