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BCL2 mutations in diffuse large B-cell lymphoma.
- Source :
-
Leukemia [Leukemia] 2012 Jun; Vol. 26 (6), pp. 1383-90. Date of Electronic Publication: 2011 Dec 22. - Publication Year :
- 2012
-
Abstract
- BCL2 is deregulated in diffuse large B-cell lymphoma (DLBCL) by the t(14;18) translocation, gene amplification and/or nuclear factor-κB signaling. RNA-seq data have recently shown that BCL2 is the most highly mutated gene in germinal center B-cell (GCB) DLBCL. We have sequenced BCL2 in 298 primary DLBCL biopsies, 131 additional non-Hodgkin lymphoma biopsies, 24 DLBCL cell lines and 51 germline DNAs. We found frequent BCL2 mutations in follicular lymphoma (FL) and GCB DLBCL, but low levels of BCL2 mutations in activated B-cell DLBCL, mantle cell lymphoma, small lymphocytic leukemia and peripheral T-cell lymphoma. We found no BCL2 mutations in GC centroblasts. Many mutations were non-synonymous; they were preferentially located in the flexible loop domain, with few in BCL2-homology domains. An elevated transition/transversions ratio supports that the mutations result from somatic hypermutation. BCL2 translocations correlate with, and are likely important in acquisition of, additional BCL2 mutations in GCB DLBCL and FL. DLBCL mutations were not independently associated with survival. Although previous studies of BCL2 mutations in FL have reported mutations to result in pseudo-negative BCL2 protein expression, we find this rare in de-novo DLBCL.
- Subjects :
- Cytogenetic Analysis
Humans
Immunoenzyme Techniques
Leukemia, Lymphocytic, Chronic, B-Cell metabolism
Lymphoma, Large B-Cell, Diffuse metabolism
Lymphoma, Mantle-Cell metabolism
Lymphoma, T-Cell, Peripheral metabolism
Mediastinal Neoplasms metabolism
Protein Transport
Proto-Oncogene Proteins c-bcl-2 metabolism
Leukemia, Lymphocytic, Chronic, B-Cell genetics
Lymphoma, Large B-Cell, Diffuse genetics
Lymphoma, Mantle-Cell genetics
Lymphoma, T-Cell, Peripheral genetics
Mediastinal Neoplasms genetics
Mutation genetics
Proto-Oncogene Proteins c-bcl-2 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1476-5551
- Volume :
- 26
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Leukemia
- Publication Type :
- Academic Journal
- Accession number :
- 22189900
- Full Text :
- https://doi.org/10.1038/leu.2011.378