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Published on: May 10, 2017
t(X;14)(p11.4;q32.33) is recurrent in marginal zone lymphoma and up-regulates GPR34
Mathijs Baens1, Julio Finalet Ferreiro, Thomas Tousseyn
1Center for Human Genetics, KU Leuven, Leuven, Belgium.
Abstract:
Genetic events underlying pathogenesis of nodal and extranodal marginal zone lymphoma are not completely understood. We report here a novel t(X;14)(p11.4;q32.33) identified in 4 lymphoma cases: 2 with a mucosa-associated lymphoid tissue lymphoma, one with a nodal marginal zone lymphoma and one with gastric diffuse large B-cell lymphoma. In all cases, lymphoma evolved from a previous auto-immune disorder. Fluorescence in situ hybridization and molecular studies showed that t(X;14), which is mediated by immunoglobulin heavy chain locus, targets the GPR34 gene at Xp11.4. Upregulation of GPR34 mRNA and aberrant expression of GPR34 protein has been demonstrated in 3 presented cases by quantitative real-time polymerase chain reaction and immunohistochemistry, respectively. GPR34 belongs to the largest family of cell surface molecules involved in signal transmission that play important roles in many physiological and pathological processes, including tumorigenesis. Although functional consequences of t(X;14) have not been identified, our studies suggest that up-regulated GPR34 activate neither nuclear factor-κB nor ELK-related tyrosine kinase.
Insights
Researchers identified a new genetic translocation, t(X;14), in four lymphoma cases, often linked to autoimmune disorders. This translocation targets the GPR34 gene, leading to its increased expression and potential role in lymphoma development.
Area of Science:
- Hematology
- Oncology
- Genetics
Background:
- The genetic underpinnings of marginal zone lymphoma (MZL) and diffuse large B-cell lymphoma (DLBCL) are not fully elucidated.
- Autoimmune disorders are increasingly recognized as risk factors for B-cell lymphomagenesis.
Purpose of the Study:
- To identify and characterize novel genetic alterations in lymphoma pathogenesis.
- To investigate the role of the GPR34 gene in lymphoma development.
Main Methods:
- Fluorescence in situ hybridization (FISH) and molecular studies to detect chromosomal translocations.
- Quantitative real-time polymerase chain reaction (qRT-PCR) to assess GPR34 mRNA levels.
- Immunohistochemistry to evaluate GPR34 protein expression.
Main Results:
- A novel t(X;14)(p11.4;q32.33) translocation was identified in four lymphoma cases, including mucosa-associated lymphoid tissue lymphoma, nodal MZL, and gastric DLBCL.
- The translocation targets the GPR34 gene at chromosome Xp11.4.
- Upregulation of GPR34 mRNA and aberrant protein expression were observed in the affected cases, which all evolved from autoimmune disorders.
Conclusions:
- The t(X;14) translocation targeting GPR34 represents a novel genetic event in lymphoma pathogenesis.
- Aberrant GPR34 expression may contribute to lymphomagenesis, particularly in the context of autoimmune diseases.
- Further functional studies are needed to elucidate the precise role of GPR34 in lymphoma signaling pathways.
