Frequent somatic hypermutation of the 5' noncoding region of the BCL6 gene in B-cell lymphoma

The BCL6 gene encodes a zinc-finger transcription factor and is altered by chromosomal rearrangements in its 5' noncoding region in approximate to 30% of diffuse large-cell lymphoma (DLCL). We report here that, in 22/30 (73%) DLCL and 7/15 (47%) follicular lymphoma (FL), but not in other tumor types, the BCL6 gene is also altered by multiple (1.3 x 10(-3)-1.6 x 10(-2) per bp), often biallelic, mutations clustering in its 5' noncoding region. These mutations are of somatic origin and are found in cases displaying either normal or rearranged BCL6 alleles indicating their independence from chromosomal rearrangements and linkage to immunoglobulin genes, These alterations identify a mechanism of genetic instability in malignant B cells and may have been selected during lymphomagenesis for their role in altering BCL6 expression.