Wagener, Rabea, Lopez, Cristina ORCID: 0000-0001-6644-1659, Kleinheinz, Kortine, Bausinger, Julia, Aukema, Sietse M., Nagel, Inga, Toprak, Umut H., Seufert, Julian, Altmueller, Janine, Thiele, Holger, Schneider, Christof, Kolarova, Julia, Park, Jeongbin, Huebschmann, Daniel, Penas, Eva M. Murga, Drexler, Hans G., Attarbaschi, Andishe, Hovland, Randi, Kjeldsen, Eigil, Kneba, Michael, Kontny, Udo, de Leval, Laurence, Nuernberg, Peter, Oschlies, Ilske, Oscier, David, Schlegelberger, Brigitte, Stilgenbauer, Stephan, Woessmann, Wilhelm, Schlesner, Matthias ORCID: 0000-0002-5896-4086, Burkhardt, Birgit, Klapper, Wolfram, Jaffe, Elaine S., Kueppers, Ralf and Siebert, Reiner (2018). IG-MYC plus neoplasms with precursor B-cell phenotype are molecularly distinct from Burkitt lymphomas. Blood, 132 (21). S. 2280 - 2286. WASHINGTON: AMER SOC HEMATOLOGY. ISSN 1528-0020

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Wagener, RabeaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lopez, CristinaUNSPECIFIEDorcid.org/0000-0001-6644-1659UNSPECIFIED
Kleinheinz, KortineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bausinger, JuliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Aukema, Sietse M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nagel, IngaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Toprak, Umut H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Seufert, JulianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Altmueller, JanineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thiele, HolgerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schneider, ChristofUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kolarova, JuliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Park, JeongbinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Huebschmann, DanielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Penas, Eva M. MurgaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Drexler, Hans G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Attarbaschi, AndisheUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hovland, RandiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kjeldsen, EigilUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kneba, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kontny, UdoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Leval, LaurenceUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nuernberg, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oschlies, IlskeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oscier, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schlegelberger, BrigitteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stilgenbauer, StephanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Woessmann, WilhelmUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schlesner, MatthiasUNSPECIFIEDorcid.org/0000-0002-5896-4086UNSPECIFIED
Burkhardt, BirgitUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klapper, WolframUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jaffe, Elaine S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kueppers, RalfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Siebert, ReinerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-165468
DOI: 10.1182/blood-2018-03-842088
Journal or Publication Title: Blood
Volume: 132
Number: 21
Page Range: S. 2280 - 2286
Date: 2018
Publisher: AMER SOC HEMATOLOGY
Place of Publication: WASHINGTON
ISSN: 1528-0020
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ACUTE LYMPHOBLASTIC-LEUKEMIA; CHROMOSOMAL TRANSLOCATIONS; MUTATIONS; LIGHTMultiple languages
HematologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/16546

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