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Mod Pathol. 2018 Sep;31(9):1418-1428. doi: 10.1038/s41379-018-0064-0. Epub 2018 May 15.

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

Author information

1
Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
2
Samsung Genome Institute, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Korea.
3
Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Korea.
4
Division of hematology-oncology, Department of Internal medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
5
Samsung Genome Institute, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Korea. woongyang@skku.edu.
6
Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. yhko310@skku.edu.

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.

PMID:
29765142
DOI:
10.1038/s41379-018-0064-0
[Indexed for MEDLINE]

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