Different primary thyroid B-cell lymphomas show overlapping mutation profiles, suggesting involvement of a common...

Area of Science:

• Oncology
• Genetics
• Immunology

Background:

• Primary thyroid lymphomas often arise from Hashimoto's thyroiditis.
• Common types include extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (EMZL), diffuse large B-cell lymphoma (DLBCL), and follicular lymphoma (FL).
• Distinct mutation profiles may exist between these thyroid lymphoma subtypes.

Purpose of the Study:

• To investigate and compare the mutation profiles of thyroid EMZL, FL, and DLBCL.
• To determine if mutation profiles can differentiate between these thyroid lymphoma types.
• To analyze the genomic configurations of BCL6 translocations in thyroid FL and EMZL.

Main Methods:

• Targeted next-generation sequencing (NGS) was used to analyze mutations in 42 EMZL, 21 FL, and 34 DLBCL thyroid samples.
• Targeted locus capture NGS was employed for genomic analysis of BCL6 translocations.

Main Results:

• Thyroid EMZL, BCL2-negative FL, and DLBCL exhibited overlapping mutation profiles, frequently involving TET2, IGLL5, TNFRSF14, CD274, GNA13, FAS, KLF2, and TNFAIP3.
• BCL2-positive FL showed distinct mutations in BCL2, KMT2D, CREBBP, and EZH2, but not TET2 or CD274.
• BCL6 translocations differed significantly between thyroid FL and EMZL, impacting BCL6 gene expression potential.

Conclusions:

• Thyroid lymphoma subtypes share common genetic alterations, suggesting a potential overlap in pathogenesis.
• Distinct BCL6 translocation mechanisms in FL and EMZL provide molecular insights into their development.
• These genetic findings contribute to understanding thyroid lymphoma pathogenesis, including the role of autoimmunity.