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The genetics of nodal marginal zone lymphoma
- Publication Year :
- 2016
-
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.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Cancer Research
Proliferation index
Lymphoma
Immunology
PTRD
Receptor-Like Protein Tyrosine Phosphatases
Splenic Neoplasm
Marginal Zone
Biology
Biomarkers, Tumor
Exome
High-Throughput Nucleotide Sequencing
Humans
Lymphoma, B-Cell, Marginal Zone
Mutation
Receptor, Notch2
Receptor-Like Protein Tyrosine Phosphatases, Class 2
Splenic Neoplasms
Biochemistry
Hematology
Cell Biology
03 medical and health sciences
Internal medicine
medicine
Splenic marginal zone lymphoma
Exome sequencing
Genetics
Notch2
marginal zone lymphomas, PTRD, molecular profile
Tumor
B-Cell
Cancer
Class 2
medicine.disease
030104 developmental biology
Oncology
molecular profile
marginal zone lymphomas
Biomarkers
Receptor
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....9ad252050a2b1201d7c165e02a4dbcf9