Targeted deep sequencing of gastric marginal zone lymphoma identified alterations of TRAF3 and TNFAIP3 that were mutually exclusive for MALT1 rearrangement

Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc
Jiyeon HyeonYoung-Hyeh Ko

Abstract

Gastric extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue is a distinct entity in that Helicobacter pylori infection plays the most important causative role in the development of the disease. To investigate the genomic alteration in gastric marginal zone lymphoma that was resistant to the H. pylori eradication therapy, we analyzed 19 cases of the gastric marginal zone lymphoma using fluorescence in situ hybridization for MALT1, BCL10 rearrangement, and targeted sequencing using an Illumina platform. Major genetic alterations affected genes involved in nuclear factor (NF)-κB pathway activation and included MALT1 rearrangement (39%), and somatic mutations of TRAF3 (21%), TNFAIP3 (16%), and NOTCH1 (16%). In the MALT1 rearrangement-negative group, disruptive somatic mutations of TRAF3 were the most common alterations (4/12, 33%), followed by somatic mutations of TNFAIP3 (3/12, 25%), and NOTCH1 (3/12, 25%). The present study confirms that genes involved in activation of NF-κB-signaling pathways are a major driver in oncogenesis of H. pylori eradication-resistant gastric marginal zone lymphoma and revealed that TRAF3 mutation is a major contributor in MALT1 rearrangement-negative gastric marginal zone lymphoma.

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Citations

Dec 13, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Samantha GokhalePing Xie
Oct 9, 2018·Frontiers in Immunology·Sining ZhuPing Xie
Aug 29, 2020·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Visar VelaThomas Menter
Oct 13, 2020·Human Pathology·Nicholas J K BaraschSteven H Swerdlow
Mar 26, 2021·Expert Review of Hematology·Barbara Kiesewetter, Markus Raderer
Apr 8, 2021·Cellular and Molecular Life Sciences : CMLS·Olga Sokolova, Michael Naumann
Aug 15, 2020·The Korean Journal of Internal Medicine·Jang Ho ChoSeok Jin Kim
May 15, 2021·Seminars in Diagnostic Pathology·Laura Toth, Mohammad A Vasef
Oct 5, 2021·Annals of Hematology·Xiaojun WangXiaoli Feng
Dec 26, 2021·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Bryan ReaSarah E Gibson

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Methods Mentioned

BETA
Exome Sequencing
biopsy
PCR
Fluorescence
ubiquitination

Software Mentioned

GATK
Quantasoft
CoMEt
MuTect
MEM
Picard
VarDict
BWA
Integrative Genomics Viewer
Lowfreq

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