IG-MYC+ neoplasms with precursor B-cell phenotype are molecularly distinct from Burkitt lymphomas

Détails

ID Serval
serval:BIB_FDC8062196BA
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
IG-MYC+ neoplasms with precursor B-cell phenotype are molecularly distinct from Burkitt lymphomas
Périodique
Blood
Auteur(s)
Wagener R., López C., Kleinheinz K., Bausinger J., Aukema S.M., Nagel I., Toprak U.H., Seufert J., Altmüller J., Thiele H., Schneider C., Kolarova J., Park J., Hübschmann D., Murga Penas E.M., Drexler H.G., Attarbaschi A., Hovland R., Kjeldsen E., Kneba M., Kontny U., de Leval L., Nürnberg P., Oschlies I., Oscier D., Schlegelberger B., Stilgenbauer S., Wössmann W., Schlesner M., Burkhardt B., Klapper W., Jaffe E.S., Küppers R., Siebert R.
ISSN
1528-0020 (Electronic)
ISSN-L
0006-4971
Statut éditorial
Publié
Date de publication
22/11/2018
Peer-reviewed
Oui
Volume
132
Numéro
21
Pages
2280-2285
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
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.
Mots-clé
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
Création de la notice
09/10/2018 10:58
Dernière modification de la notice
20/08/2019 16:28
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