title: Frequent somatic hypermutation of the 5' noncoding region of the BCL6 gene in B-cell lymphoma.
abstract: The BCL6 gene encodes a zinc-finger transcription factor and is altered by chromosomal arrangements in its 5' noncoding region in approximately 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 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 BLC6 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.
authors.affiliation: Department of Pathology, Columbia University, New York, NY 10032, USA.
authors.forename: A
authors.initials: A
authors.lastname: Migliazza
authors.forename: S
authors.initials: S
authors.lastname: Martinotti
authors.forename: W
authors.initials: W
authors.lastname: Chen
authors.forename: C
authors.initials: C
authors.lastname: Fusco
authors.forename: B H
authors.initials: BH
authors.lastname: Ye
authors.forename: D M
authors.initials: DM
authors.lastname: Knowles
authors.forename: K
authors.initials: K
authors.lastname: Offit
authors.forename: R S
authors.initials: RS
authors.lastname: Chaganti
authors.forename: R
authors.initials: R
authors.lastname: Dalla-Favera
mesh_terms: D000483:Alleles; D001483:Base Sequence; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D051560:Proto-Oncogene Proteins c-bcl-6; D011519:Proto-Oncogenes; D015183:Restriction Mapping; D017384:Sequence Deletion; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D016335:Zinc Fingers
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors