Most of CD30⁺ anaplastic large cell lymphoma of B cell type show a somatic mutation in the IgH V region genes

Abstract

Relationship and histogenesis of Hodgkin’s disease (HD) and anaplastic large cell lymphoma (ALCL) still remain unclear. Recently, Reed–Sternberg cells or Hodgkin cells in HD with B cell phenotype (B-HD) are considered to originate from germinal center B cells, ALCLs of B cell phenotype (B-ALCL) are involved in diffuse large B cell lymphoma (DLBCL) as anaplastic variant, but an origin of tumor cells of B-ALCL has not been elucidated. We have therefore investigated somatic mutation of the Ig heavy chain (IgH) genes among 17 cases of B-ALCL to clarify whether there is a difference in characteristic and origin of tumor cells between B-ALCL, B-HD and DLBCL. Amplificates of IgH variable (V) region of 10 cases by the polymerase chain reaction method were sequenced and compared with reported germ line configurations. Nine cases (90%) with heavily somatic mutations were found. A case with an out-of-frame rearrangement and a case with 9 base pairs insertion were included. The mutation pattern revealed the tumor cells were selected for antibody expression and discriminated from B-HD. These findings suggest the tumor cells of B-ALCL are derived from germinal center or postgerminal center (memory and effector) B cells and an origin of B-ALCL is not different from DLBCL.