ArticleLeukemia2001
Somatic hypermutation targeting to intrinsic hotspots of immunoglobulin genes in follicular lymphoma and multiple myeloma.
Article in Leukemia, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
2 citing papers in PubMed, 7 citations in OpenAlex.
- Adaptive T cell immunotherapy in cancer.Science China. Life sciences · 2021Review
- Immunoglobulin heavy- and light-chain repertoire in splenic marginal zone lymphoma.Molecular medicine (Cambridge, Mass.)Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In this study, we analyzed the targeting of the somatic hypermutation (SHM) mechanism at specific hotspot sequence motifs in the V(H) and Vkappa genes of 10 follicular lymphoma (FL) cases and the Vkappa and Vlambda genes of 11 kappa- and six lamda-light chain expressing multiple myeloma (MM) cases. These sequences were analyzed for targeting of specific motifs, ie certain highly mutable trinucleotides (3-NTPs), the tetranucleotide (4-NTP) RGYW and its complementary, WRCY (where R = purine, Y = pyrimidine and W = A or T). Comparisons were carried out between mutation frequencies in RGYW vs WRCY and the incidence of mutations in complementarity determining region (CDR)-1 vs CDR2 vs CDR3. Statistically significant differences were obtained when comparing: (1) the ratio of mutations in 4-NTPs (RGYW, WRCY, RGYW+WRCY)/mutations in the whole V sequence in MM-Vkappa vs MM-Vlamda; (2) the total number of mutated 4-NTPs in MM-Vkappa vs FL-Vkappa; (3) the number of mutated RGYW 4-NTPs in MM-Vkappa vs FL-Vkappa and FL-V(H) vs FL-Vkappa; (4) the number of mutated WRCY 4-NTPs in MM-Vkappa vs FL-Vkappa (P= 0.006) and FL-V(H) vs FL-Vkappa; (5) the targeting of RGYW vs WRCY in the CDRs of FL-V(H) genes. Similar results (regarding statistical significance) were obtained when undertaking intergroup comparisons for 3-NTPs. These findings conform well with relevant data derived from normal peripheral B cells. The differences observed in favor of 4-NTP (RGYW and WRCY) targeting in FL-V(H) vs FL-Vkappa and MM-Vkappa vs FL-Vkappa may implicate differences in the evolution of SHM coupled with selection in different stages of B cell ontogeny. Several explanations can be offered for the fact that hotspot sequences were not always targeted by SHM in FL and MM: (1) other unrecognized motifs may be targets of SHM; (2) 'inappropriately' introduced mutations were fixed and propagated by the neoplastic process; (3) certain FL and MM cases might have lost their ability to correct mutations introduced in classic hotspots due to deficient mismatch-repair (MMR) mechanisms; conversely, in other cases with intact MMR function, the hotspot to non-hotspot targeting of somatic hypermutation is balanced.
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