title: The genetic landscape of dural marginal zone lymphomas.
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.
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Karthik A
authors.initials: KA
authors.lastname: Ganapathi
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Vaidehi
authors.initials: V
authors.lastname: Jobanputra
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Fabio
authors.initials: F
authors.lastname: Iwamoto
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Preti
authors.initials: P
authors.lastname: Jain
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Jinli
authors.initials: J
authors.lastname: Chen
authors.affiliation: Institute of Oncology Research and Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
authors.forename: Luciano
authors.initials: L
authors.lastname: Cascione
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Odelia
authors.initials: O
authors.lastname: Nahum
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Brynn
authors.initials: B
authors.lastname: Levy
authors.affiliation: Hematopathology Section, Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Pathology, New York Medical College, Valhalla, NY, USA.
authors.forename: Pallavi
authors.initials: P
authors.lastname: Khattar
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Daniela
authors.initials: D
authors.lastname: Hoehn
authors.affiliation: Institute of Oncology Research and Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
authors.forename: Francesco
authors.initials: F
authors.lastname: Bertoni
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Vundavalli V
authors.initials: VV
authors.lastname: Murty
authors.affiliation: Hematopathology Section, Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Stefania
authors.initials: S
authors.lastname: Pittaluga
authors.affiliation: Hematopathology Section, Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Jaffe
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Bachir
authors.initials: B
authors.lastname: Alobeid
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Mahesh M
authors.initials: MM
authors.lastname: Mansukhani
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Govind
authors.initials: G
authors.lastname: Bhagat
mesh_terms: D000328:Adult; D002869:Chromosome Aberrations; D004252:DNA Mutational Analysis; D004388:Dura Mater / Q000378:metabolism* / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D008297:Male; D008577:Meningeal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D008875:Middle Aged; D009154:Mutation
keywords: NOTCH2; TNFAIP3; dural marginal zone lymphoma; genome; mutations