PURPOSE: Prompted by the extensive biases in the immunoglobulin (IG) gene repertoire of splenic marginal-zone lymphoma (SMZL), supporting antigen selection in SMZL ontogeny, we sought to investigate whether antigen involvement is also relevant post-transformation. EXPERIMENTAL DESIGN: We conducted a large-scale subcloning study of the IG rearrangements of 40 SMZL cases aimed at assessing intraclonal diversification (ID) due to ongoing somatic hypermutation (SHM). RESULTS: ID was identified in 17 of 21 (81%) rearrangements using the immunoglobulin heavy variable (IGHV)1-2*04 gene versus 8 of 19 (40%) rearrangements utilizing other IGHV genes (P= 0.001). ID was also evident in most analyzed IG light chain gene rearrangements, albeit was more limited compared with IG heavy chains. Identical sequence changes were shared by subclones from different patients utilizing the IGHV1-2*04 gene, confirming restricted ongoing SHM profiles. Non-IGHV1-2*04 cases displayed both a lower number of ongoing SHMs and a lack of shared mutations (per group of cases utilizing the same IGHV gene). CONCLUSIONS: These findings support ongoing antigen involvement in a sizable portion of SMZL and further argue that IGHV1-2*04 SMZL may represent a distinct molecular subtype of the disease.
- MeSH
- alely * MeSH
- aminokyselinové motivy MeSH
- antigeny imunologie MeSH
- biologické modely MeSH
- hypervariabilní oblasti chemie genetika MeSH
- lidé MeSH
- lymfom z B-buněk marginální zóny genetika imunologie patologie MeSH
- mutace MeSH
- nádory sleziny genetika imunologie patologie MeSH
- přestavba genů pro těžké řetězce B-lymfocytů MeSH
- receptory antigenů B-buněk genetika MeSH
- sekvence aminokyselin MeSH
- stanovení celkové genové exprese MeSH
- substituce aminokyselin MeSH
- těžké řetězce imunoglobulinů chemie genetika MeSH
- transkriptom MeSH
- variabilní oblast imunoglobulinu chemie genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
