Investigation of BCL-2 Gene Rearrangements in a United Kingdom Series of Low and High Grade Non-Hodgkin's Lymphomas

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Abstract
Rearrangements of the BCL-2 gene are thought to be the most frequent genetic changes that occur in non-Hodgkin's lymphomas (NHL), and are particularly associated with follicular low grade disease. Wide variations in the frequency of these rearrangements have, however, been reported in studies of NHL series from different parts of the world. We were therefore interested to determine the frequency of BCL-2 gene rearrangements in the different grades of NHL from a U.K. series. We have done this by using a combination of Southern blot hybridization and polymerase chain reaction (PCR) analysis. The frequencies of rearrangements in our series were 9/20 (45%) in low grade follicular NHL, 1/8 (12.5%) in low grade lymphocytic and 5/19 (26%) in high grade NHL. However, estimation of the high grade value was complicated by the fact that a number of the high grade samples in our series were from patients who had transformed from low grade follicular disease. If the patients were ranked on the basis of whether they had a history of low grade follicular disease then the frequency of BCL-2 rearrangement remained the same 13/29 (45%), but was only 1/10 (10%) in high grade NHL with no history of follicular disease. The former figure was intermediate between those reported for the USA and Japan series, but the latter high grade figure was the lowest reported from any series. The significance of BCL-2 rearrangements in the evolution of both low and high grade NHL is discussed.