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A Short Mutational Hot Spot in the First Intron of BCL-6 Is Associated with Increased BCL-6 Expression and with Longer Overall Survival in Large B-Cell Lymphomas
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A Short Mutational Hot Spot in the First Intron of BCL-6 Is Associated with Increased BCL-6 Expression and with Longer Overall Survival in Large B-Cell Lymphomas
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A Short Mutational Hot Spot in the First Intron of BCL-6 Is Associated with Increased BCL-6 Expression and with Longer Overall Survival in Large B-Cell Lymphomas
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Journal Article
A Short Mutational Hot Spot in the First Intron of BCL-6 Is Associated with Increased BCL-6 Expression and with Longer Overall Survival in Large B-Cell Lymphomas
2002
Overview
BCL-6 somatic mutations have been described in normal and tumoral B lymphocytes, associated with germinal center transit. We analyzed mutations in the major mutation cluster of BCL-6 in a series of 45 large B-cell lymphomas (LBCLs) and 15 Burkitt's lymphomas, and their relation to the level of BCL-6 expression and clinical outcome. Mutations in LBCL cases revealed the existence of two distinct, short mutational hot spots, spanning positions 106 to 127 and 423 to 443, in which the mutation frequency was higher than expected (
P < 0.001). Mutations in the 423 to 443 subcluster were associated with an increased level of expression, although this was not the case with the 106 to 127 cluster. Additionally, LBCL cases characterized by the presence of mutations in the 423 to 443 cluster showed an increased overall survival (
P < 0.05) when compared with the nonmutated LBCL cases in these positions. Burkitt's lymphoma cases showed a slightly lower frequency of mutations with a nonclustered distribution and lacked any relationship with the level of expression or any clinical characteristic. Findings from LBCLs suggest that the 423 to 443 cluster includes a regulatory region that is of importance for BCL-6 expression. Deregulation of BCL-6 expression caused by these mutations could play an important role in lymphoma genesis or progression.
Publisher
Elsevier Inc,ASIP,American Society for Investigative Pathology
Subject
Biological and medical sciences
/ DNA-Binding Proteins - genetics
/ DNA-Binding Proteins - metabolism
/ Hematologic and hematopoietic diseases
/ Humans
/ Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
/ Lymphoma, B-Cell - metabolism
/ Mutation
/ Proto-Oncogene Proteins - genetics
/ Proto-Oncogene Proteins - metabolism
/ Proto-Oncogene Proteins c-bcl-6
/ Regular
