An Immunogenetic Signature of Ongoing Antigen Interactions in Splenic Marginal Zone Lymphoma Expressing IGHV1-2*04 Receptors

• Authors: BIKOS Vasileios; KARYPIDOU Maria; STALIKA Evangelia; BALIAKAS Panagiotis; XOCHELLI Aliki; SUTTON Lesley-Ann; PAPADOPOULOS George; AGATHANGELIDIS Andreas; PAPADOPOULOU Evdoxia; DAVIS Zadie; ALGARA Patricia; KANELLIS George; TRAVERSE-GLEHEN Alexandra; MOLLEJO Manuela; ANAGNOSTOPOULOS Achilles; PONZONI Maurilio; GONZALEZ David; POSPÍŠILOVÁ Šárka; MATUTES Estella; PIRIS Miguel Angel; PAPADAKI Theodora; GHIA Paolo; ROSENQUIST Richard; OSCIER David; DARZENTAS Nikos; TZOVARAS Dimitros; BELESSI Chrysoula; HADZIDIMITRIOU Anastasia; STAMATOPOULOS Kostas
• Year of publication: 2016
• Type: Article in Periodical
• Magazine / Source: Clinical cancer research
• MU Faculty or unit: Central European Institute of Technology
• web: http://clincancerres.aacrjournals.org/content/22/8/2032
• Doi: http://dx.doi.org/10.1158/1078-0432.CCR-15-1170
• Field: Oncology and hematology
• Keywords: HRONIC LYMPHOCYTIC-LEUKEMIA; SOMATIC HYPERMUTATION; V-H; IMMUNOGLOBULIN GENES; DATA-COMPRESSION; CELL-RECEPTOR; LIGHT-CHAIN; SEQUENCE; MUTATION; ANTIBODIES
• Description: 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. (C) 2015 AACR.

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