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

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.

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

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Item Type:	Article
Title:	IG-MYC(+) neoplasms with precursor B-cell phenotype are molecularly distinct from Burkitt lymphomas
Creators:	Wagener, R., López, C., Kleinheinz, K., Bausinger, J., Aukema, S.M., Nagel, I., Toprak, U.H., Seufert, J., Altmüller, J. ORCID: https://orcid.org/0000-0003-4372-1521, 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. and Siebert, R.
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:	B-Lymphocyte Gene Rearrangement, B-Lymphoid Precursor Cells, Burkitt Lymphoma, DNA Methylation, Genetic Translocation, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Proto-Oncogene Proteins c-myc, Retrospective Studies, V(D)J Recombination
Source:	Blood
ISSN:	0006-4971
Publisher:	American Society of Hematology
Volume:	132
Number:	21
Page Range:	2280-2285
Date:	22 November 2018
Official Publication:	https://doi.org/10.1182/blood-2018-03-842088
PubMed:	View item in PubMed

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