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

Anna Migliazza, Stefano Martinotti, Weiyi Chen, Carlo Fusco, Bihui Ye, Daniel M. Knowles, Kenneth Offit, R. S.K. Chaganti, Riccardo Dalla-Favera

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314 Scopus citations

Abstract

The BCL6 gene encodes a zinc-finger transcription factor and is altered by chromosomal rearrangements in its 5′ noncoding region in ≈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 (1.4 × 10-3-1.6 × 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.

Original languageEnglish (US)
Pages (from-to)12520-12524
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number26
DOIs
StatePublished - Dec 19 1995
Externally publishedYes

ASJC Scopus subject areas

  • General

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