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Blood. 2016 Sep 8;128(10):1362-73. doi: 10.1182/blood-2016-02-696757. Epub 2016 Jun 22.

The genetics of nodal marginal zone lymphoma.

Author information

1
Division of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy;
2
Department of Biomedical Informatics and Systems Biology, Columbia University, New York, NY;
3
Division of Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome, Italy;
4
Institute of Oncology Research and Oncology Institute of Southern Switzerland, Bellinzona, Switzerland;
5
Institute for Cancer Genetics and the Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY;
6
Department of Hematology-Oncology, Fondazione IRCCS Policlinico San Matteo and Department of Molecular Medicine, University of Pavia, Pavia, Italy;
7
Division of Pathology, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy;
8
Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY;
9
Division of Hematology, Department of Oncology and Hematology, University of Modena and Reggio Emilia, Modena, Italy;
10
Ateneo Vita-Salute and Unit of Lymphoid Malignancies, San Raffaele H. Scientific Institute, Milan, Italy;
11
Department of Medical Sciences, University of Torino and Immunogenetics Unit, Human Genetics Foundation, Torino, Italy;
12
Division of Pathology, Department of Health Sciences, Amedeo Avogadro University of Eastern Piedmont and Maggiore Hospital, Novara, Italy;
13
Institute of Hematology, Ospedale S. Maria della Misericordia, University of Perugia, Perugia, Italy;
14
Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY; Department of Molecular Biotechnology and Health Science and Center for Experimental Research and Medical Studies, University of Torino, Torino, Italy; and Department of Pathology, NYU Cancer Center, New York University School of Medicine, New York, NY.
15
Division of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy; Institute of Oncology Research and Oncology Institute of Southern Switzerland, Bellinzona, Switzerland;

Abstract

Nodal marginal zone lymphoma (NMZL) is a rare, indolent B-cell tumor that is distinguished from splenic marginal zone lymphoma (SMZL) by the different pattern of dissemination. NMZL still lacks distinct markers and remains orphan of specific cancer gene lesions. By combining whole-exome sequencing, targeted sequencing of tumor-related genes, whole-transcriptome sequencing, and high-resolution single nucleotide polymorphism array analysis, we aimed at disclosing the pathways that are molecularly deregulated in NMZL and we compare the molecular profile of NMZL with that of SMZL. These analyses identified a distinctive pattern of nonsilent somatic lesions in NMZL. In 35 NMZL patients, 41 genes were found recurrently affected in ≥3 (9%) cases, including highly prevalent molecular lesions of MLL2 (also known as KMT2D; 34%), PTPRD (20%), NOTCH2 (20%), and KLF2 (17%). Mutations of PTPRD, a receptor-type protein tyrosine phosphatase regulating cell growth, were enriched in NMZL across mature B-cell tumors, functionally caused the loss of the phosphatase activity of PTPRD, and were associated with cell-cycle transcriptional program deregulation and increased proliferation index in NMZL. Although NMZL shared with SMZL a common mutation profile, NMZL harbored PTPRD lesions that were otherwise absent in SMZL. Collectively, these findings provide new insights into the genetics of NMZL, identify PTPRD lesions as a novel marker for this lymphoma across mature B-cell tumors, and support the distinction of NMZL as an independent clinicopathologic entity within the current lymphoma classification.

PMID:
27335277
PMCID:
PMC5016706
DOI:
10.1182/blood-2016-02-696757
[Indexed for MEDLINE]
Free PMC Article

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