IG-MYC+ neoplasms with precursor B-cell phenotype are molecularly distinct from Burkitt lymphomas
Details
Serval ID
serval:BIB_FDC8062196BA
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
IG-MYC+ neoplasms with precursor B-cell phenotype are molecularly distinct from Burkitt lymphomas
Journal
Blood
ISSN
1528-0020 (Electronic)
ISSN-L
0006-4971
Publication state
Published
Issued date
22/11/2018
Peer-reviewed
Oui
Volume
132
Number
21
Pages
2280-2285
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
The WHO Classification of Tumours of Haematopoietic and Lymphoid Tissue notes instances of Burkitt lymphoma/leukemia (BL) with IG-MYC rearrangement displaying a B-cell precursor immunophenotype (termed herein "preBLL"). To characterize the molecular pathogenesis of preBLL, we investigated 13 preBLL cases (including 1 cell line), of which 12 were analyzable using genome, exome, and targeted sequencing, imbalance mapping, and DNA methylation profiling. In 5 patients with reads across the IG-MYC breakpoint junctions, we found evidence that the translocation derived from an aberrant VDJ recombination, as is typical for IG translocations arising in B-cell precursors. Genomic changes like biallelic IGH translocations or VDJ rearrangements combined with translocation into the VDJ region on the second allele, potentially preventing expression of a productive immunoglobulin, were detected in 6 of 13 cases. We did not detect mutations in genes frequently altered in BL, but instead found activating NRAS and/or KRAS mutations in 7 of 12 preBLLs. Gains on 1q, recurrent in BL and preB lymphoblastic leukemia/lymphoma (pB-ALL/LBL), were detected in 7 of 12 preBLLs. DNA methylation profiling showed preBLL to cluster with precursor B cells and pB-ALL/LBL, but apart from BL. We conclude that preBLL genetically and epigenetically resembles pB-ALL/LBL rather than BL. Therefore, we propose that preBLL be considered as a pB-ALL/LBL with recurrent genetic abnormalities.
Keywords
Adolescent, Adult, Aged, Burkitt Lymphoma/diagnosis, Burkitt Lymphoma/genetics, Burkitt Lymphoma/pathology, Child, Child, Preschool, DNA Methylation, Female, Gene Rearrangement, B-Lymphocyte, Humans, Male, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis, Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics, Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology, Precursor Cells, B-Lymphoid/metabolism, Precursor Cells, B-Lymphoid/pathology, Proto-Oncogene Proteins c-myc/genetics, Retrospective Studies, Translocation, Genetic, V(D)J Recombination, Young Adult
Pubmed
Web of science
Create date
09/10/2018 11:58
Last modification date
20/08/2019 17:28