An Immunogenetic Signature of Ongoing Antigen Interactions in Splenic Marginal Zone Lymphoma Expressing IGHV1-2*04 Receptors
2016 (English)In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 22, no 8, 2032-2040 p.Article in journal (Refereed) PublishedText
G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece.;Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic..
G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece.;CERTH, Inst Appl Biosci, Thessaloniki, Greece..
CERTH, Inst Appl Biosci, Thessaloniki, Greece..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
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.
Place, publisher, year, edition, pages
2016. Vol. 22, no 8, 2032-2040 p.
Cancer and Oncology
IdentifiersURN: urn:nbn:se:uu:diva-300303DOI: 10.1158/1078-0432.CCR-15-1170ISI: 000374101400024PubMedID: 26647217OAI: oai:DiVA.org:uu-300303DiVA: diva2:951351