An immunogenetic signature of ongoing antigen interactions in splenic marginal zone lymphoma expressing IGHV1-2∗04 receptors

Vasilis Bikos, Maria Karypidou, Evangelia Stalika, Panagiotis Baliakas, Aliki Xochelli, Lesley Ann Sutton, George Papadopoulos, Andreas Agathangelidis, Evdoxia Papadopoulou, Zadie Davis, Patricia Algara, George Kanellis, Alexandra Traverse-Glehen, Manuela Mollejo, Achilles Anagnostopoulos, Maurilio Ponzoni, David Gonzalez, Sarka Pospisilova, Estella Matutes, Miguel Angel PirisTheodora Papadaki, Paolo Ghia, Richard Rosenquist, David Oscier, Nikos Darzentas, Dimitrios Tzovaras, Chrysoula Belessi, Anastasia Hadzidimitriou, Kostas Stamatopoulos

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)2032-2040
Number of pages9
JournalClinical Cancer Research
Volume22
Issue number8
DOIs
Publication statusPublished - Apr 15 2016

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Bikos, V., Karypidou, M., Stalika, E., Baliakas, P., Xochelli, A., Sutton, L. A., Papadopoulos, G., Agathangelidis, A., Papadopoulou, E., Davis, Z., Algara, P., Kanellis, G., Traverse-Glehen, A., Mollejo, M., Anagnostopoulos, A., Ponzoni, M., Gonzalez, D., Pospisilova, S., Matutes, E., ... Stamatopoulos, K. (2016). An immunogenetic signature of ongoing antigen interactions in splenic marginal zone lymphoma expressing IGHV1-2∗04 receptors. Clinical Cancer Research, 22(8), 2032-2040. https://doi.org/10.1158/1078-0432.CCR-15-1170