Biclonality of gastric lymphomas

Area of Science:

• Hematologic Oncology
• Molecular Pathology
• Gastrointestinal Cancer Research

Background:

• The clonal evolution and pathogenesis of gastric diffuse large B-cell lymphoma (DLBCL) remain subjects of debate.
• The relationship between gastric DLBCL and extranodal marginal zone B-cell lymphoma (MZBL), MALT type, is not fully understood.

Purpose of the Study:

• To investigate the clonality of morphologically distinct areas within gastric lymphomas.
• To determine the genetic relationship between different components of gastric lymphomas, including DLBCL and MZBL, MALT type.

Main Methods:

• Analysis of six gastric lymphomas: two MZBL (MALT type), two DLBCL, and two composite lymphomas.
• Laser capture microdissection to isolate distinct tumor areas.
• Polymerase chain reaction (PCR)-based amplification and sequencing of immunoglobulin heavy chain (IgH) gene rearrangements, including CDR3 regions.

Main Results:

• One DLBCL case exhibited a biclonal pattern with distinct IgH gene rearrangements, suggesting no common origin.
• Two composite lymphomas (DLBCL with MZBL, MALT type areas) were biclonal, showing different IgH rearrangements in small and large cell components.
• Three cases (one DLBCL, two MZBL MALT type) displayed identical IgH gene rearrangements across different tumor areas, indicating a single clone.

Conclusions:

• Gastric DLBCL can be composed of multiple distinct tumor cell clones.
• DLBCL may arise de novo rather than exclusively through transformation of low-grade lymphomas.
• The emergence of new tumor clones complicates molecular diagnostics and monitoring of gastric DLBCL.