Oncotarget

Research Papers:

The genetic landscape of dural marginal zone lymphomas

Karthik A. Ganapathi, Vaidehi Jobanputra, Fabio Iwamoto, Preti Jain, Jinli Chen, Luciano Cascione, Odelia Nahum, Brynn Levy, Yi Xie, Pallavi Khattar, Daniela Hoehn, Francesco Bertoni, Vundavalli V. Murty, Stefania Pittaluga, Elaine S. Jaffe, Bachir Alobeid, Mahesh M. Mansukhani and Govind Bhagat _

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Oncotarget. 2016; 7:43052-43061. https://doi.org/10.18632/oncotarget.9678

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Abstract

Karthik A. Ganapathi1, Vaidehi Jobanputra1, Fabio Iwamoto2, Preti Jain1, Jinli Chen1, Luciano Cascione3, Odelia Nahum1, Brynn Levy1, Yi Xie4, Pallavi Khattar5, Daniela Hoehn1, Francesco Bertoni3, Vundavalli V. Murty1, Stefania Pittaluga4, Elaine S. Jaffe4, Bachir Alobeid1, Mahesh M. Mansukhani1,* and Govind Bhagat1,*

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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