Quantifying the role of aberrant somatic hypermutation in transformation of follicular lymphoma
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Updated: Jul 8, 2026
Analysis of Somatic Hypermutation in the JH4 intron of Germinal Center B cells from Mouse Peyer's Patches
Published on: April 20, 2021
Anna Margrét Halldórsdóttir1, Margareta Frühwirth, Alexander Deutsch
1Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
Abstract:
Somatic hypermutation (SHM) aberrantly targets proto-oncogenes in various non-Hodgkin's lymphoma. To test the association of SHM with transformation of follicular lymphoma (FL), we sequenced mutational hot spots in five proto-oncogenes (BCL6, PAX5, RHOH, MYC and PIM1) in 32 low-grade FL (lgFL) with follicular histology and 26 transformed FL (tFL) with diffuse large cell histology. No difference was detected in the fraction of specimens mutated (75% of lgFL and 77% of tFL) or in the mutation load (0.08 for lgFL vs. 0.06 mutations/100 bp/allele for tFL). Serial specimens were examined from 25 patients showing stable low-grade FL (slgFL; n=6) or a low-grade FL that later transformed into diffuse large cell lymphoma (tFL; n=19). slgFL and tFL patients accumulated similar numbers of mutations in the interval between biopsies. These data indicate that mutations attributable to aberrant SHM occur with similar frequency in low-grade and transformed FL; transformation is not associated with a higher rate of aberrant SHM. Moreover, the frequency of mutations attributable to aberrant SHM in tFL was significantly lower than that reported for de novo diffuse large B cell lymphoma, suggesting differing oncogenic mechanisms in transformed follicular lymphoma and de novo diffuse large B cell lymphoma.
Insights
Somatic hypermutation (SHM) rates are similar in low-grade and transformed follicular lymphoma (FL). Transformation to diffuse large B cell lymphoma does not involve increased aberrant SHM, suggesting different oncogenic pathways.
Area of Science:
- Oncology
- Genetics
- Immunology
Background:
- Somatic hypermutation (SHM) can aberrantly target proto-oncogenes in non-Hodgkin's lymphoma.
- Understanding SHM's role in follicular lymphoma (FL) transformation is crucial for identifying oncogenic mechanisms.
Purpose of the Study:
- To investigate the association between SHM and the transformation of low-grade FL (lgFL) to transformed FL (tFL).
- To compare SHM rates in lgFL, tFL, and de novo diffuse large B cell lymphoma (DLBCL).
Main Methods:
- Sequencing of proto-oncogene mutational hotspots (BCL6, PAX5, RHOH, MYC, PIM1) in lgFL and tFL specimens.
- Analysis of mutation frequency and load in serial biopsies from patients with stable or transforming FL.
Main Results:
- No significant difference in mutation fraction or load was observed between lgFL and tFL.
- Patients with stable or transforming FL accumulated similar numbers of mutations between biopsies.
- SHM rates in tFL were lower than those reported for de novo DLBCL.
Conclusions:
- Aberrant SHM occurs at similar frequencies in both low-grade and transformed FL.
- Transformation of FL is not driven by an increased rate of aberrant SHM.
- Transformed FL and de novo DLBCL likely involve distinct oncogenic mechanisms.
