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

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IG- neoplasms with precursor B-cell phenotype are molecularly distinct from Burkitt lymphomas. / Wagener, Rabea; López, Cristina; Kleinheinz, Kortine; Bausinger, Julia; Aukema, Sietse M; Nagel, Inga; Toprak, Umut H; Seufert, Julian; Altmüller, Janine; Thiele, Holger; Schneider, Christof; Kolarova, Julia; Park, Jeongbin; Hübschmann, Daniel; Murga Penas, Eva M; Drexler, Hans G; Attarbaschi, Andishe; Hovland, Randi; Kjeldsen, Eigil; Kneba, Michael; Kontny, Udo; de Leval, Laurence; Nürnberg, Peter; Oschlies, Ilske; Oscier, David; Schlegelberger, Brigitte; Stilgenbauer, Stephan; Wössmann, Wilhelm; Schlesner, Matthias; Burkhardt, Birgit; Klapper, Wolfram; Jaffe, Elaine S; Küppers, Ralf; Siebert, Reiner.

In: BLOOD, Vol. 132, No. 21, 22.11.2018, p. 2280-2285.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Wagener, R, López, C, Kleinheinz, K, Bausinger, J, Aukema, SM, Nagel, I, Toprak, UH, Seufert, J, Altmüller, J, Thiele, H, Schneider, C, Kolarova, J, Park, J, Hübschmann, D, Murga Penas, EM, Drexler, HG, 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, ES, Küppers, R & Siebert, R 2018, 'IG- neoplasms with precursor B-cell phenotype are molecularly distinct from Burkitt lymphomas', BLOOD, vol. 132, no. 21, pp. 2280-2285. https://doi.org/10.1182/blood-2018-03-842088

APA

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., ... Siebert, R. (2018). IG- neoplasms with precursor B-cell phenotype are molecularly distinct from Burkitt lymphomas. BLOOD, 132(21), 2280-2285. https://doi.org/10.1182/blood-2018-03-842088

Vancouver

Wagener R, López C, Kleinheinz K, Bausinger J, Aukema SM, Nagel I et al. IG- neoplasms with precursor B-cell phenotype are molecularly distinct from Burkitt lymphomas. BLOOD. 2018 Nov 22;132(21):2280-2285. https://doi.org/10.1182/blood-2018-03-842088

Bibtex

@article{4e7b0c329d054788884ef7e6bcc9b221,
title = "IG- neoplasms with precursor B-cell phenotype are molecularly distinct from Burkitt lymphomas",
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 = "Journal Article",
author = "Rabea Wagener and Cristina L{\'o}pez and Kortine Kleinheinz and Julia Bausinger and Aukema, {Sietse M} and Inga Nagel and Toprak, {Umut H} and Julian Seufert and Janine Altm{\"u}ller and Holger Thiele and Christof Schneider and Julia Kolarova and Jeongbin Park and Daniel H{\"u}bschmann and {Murga Penas}, {Eva M} and Drexler, {Hans G} and Andishe Attarbaschi and Randi Hovland and Eigil Kjeldsen and Michael Kneba and Udo Kontny and {de Leval}, Laurence and Peter N{\"u}rnberg and Ilske Oschlies and David Oscier and Brigitte Schlegelberger and Stephan Stilgenbauer and Wilhelm W{\"o}ssmann and Matthias Schlesner and Birgit Burkhardt and Wolfram Klapper and Jaffe, {Elaine S} and Ralf K{\"u}ppers and Reiner Siebert",
year = "2018",
month = nov,
day = "22",
doi = "10.1182/blood-2018-03-842088",
language = "English",
volume = "132",
pages = "2280--2285",
journal = "BLOOD",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "21",

}

RIS

TY - JOUR

T1 - IG- neoplasms with precursor B-cell phenotype are molecularly distinct from Burkitt lymphomas

AU - Wagener, Rabea

AU - López, Cristina

AU - Kleinheinz, Kortine

AU - Bausinger, Julia

AU - Aukema, Sietse M

AU - Nagel, Inga

AU - Toprak, Umut H

AU - Seufert, Julian

AU - Altmüller, Janine

AU - Thiele, Holger

AU - Schneider, Christof

AU - Kolarova, Julia

AU - Park, Jeongbin

AU - Hübschmann, Daniel

AU - Murga Penas, Eva M

AU - Drexler, Hans G

AU - Attarbaschi, Andishe

AU - Hovland, Randi

AU - Kjeldsen, Eigil

AU - Kneba, Michael

AU - Kontny, Udo

AU - de Leval, Laurence

AU - Nürnberg, Peter

AU - Oschlies, Ilske

AU - Oscier, David

AU - Schlegelberger, Brigitte

AU - Stilgenbauer, Stephan

AU - Wössmann, Wilhelm

AU - Schlesner, Matthias

AU - Burkhardt, Birgit

AU - Klapper, Wolfram

AU - Jaffe, Elaine S

AU - Küppers, Ralf

AU - Siebert, Reiner

PY - 2018/11/22

Y1 - 2018/11/22

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1182/blood-2018-03-842088

DO - 10.1182/blood-2018-03-842088

M3 - SCORING: Journal article

C2 - 30282799

VL - 132

SP - 2280

EP - 2285

JO - BLOOD

JF - BLOOD

SN - 0006-4971

IS - 21

ER -