A Mottok1, M-L Hansmann, A Bräuninger. 1. Department of Pathology, University of Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
Abstract
BACKGROUND: The lymphocytic and histiocytic (L&H) cells of lymphocyte predominant Hodgkin lymphoma (HL) originate from germinal centre B cells and carry mutated V gene rearrangements, usually with intraclonal diversity. It is unclear whether intraclonal V gene diversification by somatic hypermutation, which is strictly dependent on the enzyme activation induced cytidine deaminase (AID), is restricted to the early phase of lymphoma clone expansion and later silenced, or whether it remains active throughout malignant proliferation. AIMS: To analyse whether AID is expressed in L&H cells as an indicator of active somatic hypermutation in the tumour cells. METHODS: L&H cells from lymphocyte predominant HL cases and centroblasts from lymphadenites were micromanipulated and analysed for AID expression by quantitative real time polymerase chain reaction. RESULTS: The AID transcription level was higher than background in three of the six lymphocyte predominant HL cases, although it was lower than that seen in centroblasts. CONCLUSIONS: Somatic hypermutation may remain active in L&H cells in a considerable proportion of cases, increasing the risk of acquiring further transforming mutations.
BACKGROUND: The lymphocytic and histiocytic (L&H) cells of lymphocyte predominant Hodgkin lymphoma (HL) originate from germinal centre B cells and carry mutated V gene rearrangements, usually with intraclonal diversity. It is unclear whether intraclonal V gene diversification by somatic hypermutation, which is strictly dependent on the enzyme activation induced cytidine deaminase (AID), is restricted to the early phase of lymphoma clone expansion and later silenced, or whether it remains active throughout malignant proliferation. AIMS: To analyse whether AID is expressed in L&H cells as an indicator of active somatic hypermutation in the tumour cells. METHODS: L&H cells from lymphocyte predominant HL cases and centroblasts from lymphadenites were micromanipulated and analysed for AID expression by quantitative real time polymerase chain reaction. RESULTS: The AID transcription level was higher than background in three of the six lymphocyte predominant HL cases, although it was lower than that seen in centroblasts. CONCLUSIONS: Somatic hypermutation may remain active in L&H cells in a considerable proportion of cases, increasing the risk of acquiring further transforming mutations.
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