HISTOLOGICAL CONVERSION OF FOLLICULAR LYMPHOMA WITH STRUCTURAL ALTERATIONS OF T(14-18) AND IMMUNOGLOBULIN GENES

About half of the patients with follicular lymphoma will develop an ag gressive B cell lymphoma with morphological changes in growth pattern and cellular morphology. Changes of the immunophenotype, especially of the expression of immunoglobulin (Ig) have been documented less frequ ently. Multiple tumor samples of two patients with follicular lymphoma who developed tumor progression, were studied by Southern blot analys is for rearrangements of the Ig genes and the oncogenes BCL2 and MYC. In both patients, the general pattern of Ig gene rearrangements, espec ially of the Ig light-chain genes, and the structure of the t(14;18) b reakpoint as assessed by the polymerase chain reacton (PRC) and fine r estriction mapping, remained unaltered with time. However, both within the functional Ig heavy-chain allele and around the t(14;18) breakpoi nt, extensive secondary alterations took place. This indicates clonal evolution rather than the appearance of an independent lymphoma. In th e first case with progression from follicular lymphoma to Burkitt's ly mphoma 3 years after diagnosis, alterations were especially present 3' of the t(14;18) breakpoint. In the second patient with a change from follicular to diffuse centroblastic lymphoma 4 years after diagnosis, subsequent class switches from IgM to IgG and to defective IgH express ion were accompanied by deletion of C mu sequences and a rearrangement of the MYC gene, respectively. Additionally, in both patients alterat ions in individual restriction sites occurred, which most likely were due to somatic mutations within both the functional IgH and translocat ed allele. Our data indicate that complex alterations of both the func tional and non-functional IgH allele may accompany tumor progression a nd may erroneously suggest the appearance of independent clones by Sou thern blot analysis. It remains to be established whether these altera tions are causative events or the consequence of genetic instability a nd clonal evolution.