Somatic copy number gains in MYC, BCL2, and BCL6 identifies a subset of aggressive alternative-DH/TH DLBCL patients

Jordan E. Krull; Kerstin Wenzl; Keenan T. Hartert; Michelle K. Manske; Vivekananda Sarangi; Matthew J. Maurer; Melissa C. Larson; Grzegorz S. Nowakowski; Stephen M. Ansell; Ellen McPhail; Thomas M. Habermann; Brian K. Link; Rebecca L. King; James R. Cerhan; Anne J. Novak

doi:10.1038/s41408-020-00382-3

Somatic copy number gains in MYC, BCL2, and BCL6 identifies a subset of aggressive alternative-DH/TH DLBCL patients

Jordan E. Krull, Kerstin Wenzl, Keenan T. Hartert, Michelle K. Manske, Vivekananda Sarangi, Matthew J. Maurer, Melissa C. Larson, Grzegorz S. Nowakowski, Stephen M. Ansell, Ellen McPhail, Thomas M. Habermann, Brian K. Link, Rebecca L. King, James R. Cerhan, Anne J. Novak

Research output: Contribution to journal › Article › peer-review

Abstract

Double/triple hit lymphoma (DH/TH), known as high-grade B-cell lymphoma (HGBL), is an aggressive diffuse large B cell lymphoma (DLBCL), defined as having concurrent MYC, BCL2, and/or BCL6 gene rearrangements. While gene rearrangements represent significant genetic events in cancer, copy number alterations (CNAs) also play an important role, and their contributions to rearrangements have yet to be fully elucidated. Using FISH and high-resolution CNA data, we defined the landscape of concurrent gene rearrangements and copy gains in MYC, BCL2, and BCL6, in a cohort of 479 newly diagnosed DLBCL. We also show that concurrent translocations and copy number alterations, in combinations similar to DH/TH, identify a unique subset of DLBCL, alternative DH/TH, that have survival outcomes similar to DH/TH DLBCL patients.

Original language	English (US)
Article number	117
Journal	Blood cancer journal
Volume	10
Issue number	11
DOIs	https://doi.org/10.1038/s41408-020-00382-3
State	Published - Nov 2020

ASJC Scopus subject areas

Hematology
Oncology

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Krull, J. E., Wenzl, K., Hartert, K. T., Manske, M. K., Sarangi, V., Maurer, M. J., Larson, M. C., Nowakowski, G. S., Ansell, S. M., McPhail, E., Habermann, T. M., Link, B. K., King, R. L., Cerhan, J. R., & Novak, A. J. (2020). Somatic copy number gains in MYC, BCL2, and BCL6 identifies a subset of aggressive alternative-DH/TH DLBCL patients. Blood cancer journal, 10(11), Article 117. https://doi.org/10.1038/s41408-020-00382-3

Krull, JE, Wenzl, K, Hartert, KT, Manske, MK, Sarangi, V, Maurer, MJ, Larson, MC, Nowakowski, GS , Ansell, SM , McPhail, E , Habermann, TM, Link, BK, King, RL, Cerhan, JR & Novak, AJ 2020, 'Somatic copy number gains in MYC, BCL2, and BCL6 identifies a subset of aggressive alternative-DH/TH DLBCL patients', Blood cancer journal, vol. 10, no. 11, 117. https://doi.org/10.1038/s41408-020-00382-3

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title = "Somatic copy number gains in MYC, BCL2, and BCL6 identifies a subset of aggressive alternative-DH/TH DLBCL patients",

abstract = "Double/triple hit lymphoma (DH/TH), known as high-grade B-cell lymphoma (HGBL), is an aggressive diffuse large B cell lymphoma (DLBCL), defined as having concurrent MYC, BCL2, and/or BCL6 gene rearrangements. While gene rearrangements represent significant genetic events in cancer, copy number alterations (CNAs) also play an important role, and their contributions to rearrangements have yet to be fully elucidated. Using FISH and high-resolution CNA data, we defined the landscape of concurrent gene rearrangements and copy gains in MYC, BCL2, and BCL6, in a cohort of 479 newly diagnosed DLBCL. We also show that concurrent translocations and copy number alterations, in combinations similar to DH/TH, identify a unique subset of DLBCL, alternative DH/TH, that have survival outcomes similar to DH/TH DLBCL patients.",

author = "Krull, {Jordan E.} and Kerstin Wenzl and Hartert, {Keenan T.} and Manske, {Michelle K.} and Vivekananda Sarangi and Maurer, {Matthew J.} and Larson, {Melissa C.} and Nowakowski, {Grzegorz S.} and Ansell, {Stephen M.} and Ellen McPhail and Habermann, {Thomas M.} and Link, {Brian K.} and King, {Rebecca L.} and Cerhan, {James R.} and Novak, {Anne J.}",

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doi = "10.1038/s41408-020-00382-3",

language = "English (US)",

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AU - Krull, Jordan E.

AU - Wenzl, Kerstin

AU - Hartert, Keenan T.

AU - Manske, Michelle K.

AU - Sarangi, Vivekananda

AU - Maurer, Matthew J.

AU - Larson, Melissa C.

AU - Nowakowski, Grzegorz S.

AU - Ansell, Stephen M.

AU - McPhail, Ellen

AU - Habermann, Thomas M.

AU - Link, Brian K.

AU - King, Rebecca L.

AU - Cerhan, James R.

AU - Novak, Anne J.

PY - 2020/11

Y1 - 2020/11

N2 - Double/triple hit lymphoma (DH/TH), known as high-grade B-cell lymphoma (HGBL), is an aggressive diffuse large B cell lymphoma (DLBCL), defined as having concurrent MYC, BCL2, and/or BCL6 gene rearrangements. While gene rearrangements represent significant genetic events in cancer, copy number alterations (CNAs) also play an important role, and their contributions to rearrangements have yet to be fully elucidated. Using FISH and high-resolution CNA data, we defined the landscape of concurrent gene rearrangements and copy gains in MYC, BCL2, and BCL6, in a cohort of 479 newly diagnosed DLBCL. We also show that concurrent translocations and copy number alterations, in combinations similar to DH/TH, identify a unique subset of DLBCL, alternative DH/TH, that have survival outcomes similar to DH/TH DLBCL patients.

AB - Double/triple hit lymphoma (DH/TH), known as high-grade B-cell lymphoma (HGBL), is an aggressive diffuse large B cell lymphoma (DLBCL), defined as having concurrent MYC, BCL2, and/or BCL6 gene rearrangements. While gene rearrangements represent significant genetic events in cancer, copy number alterations (CNAs) also play an important role, and their contributions to rearrangements have yet to be fully elucidated. Using FISH and high-resolution CNA data, we defined the landscape of concurrent gene rearrangements and copy gains in MYC, BCL2, and BCL6, in a cohort of 479 newly diagnosed DLBCL. We also show that concurrent translocations and copy number alterations, in combinations similar to DH/TH, identify a unique subset of DLBCL, alternative DH/TH, that have survival outcomes similar to DH/TH DLBCL patients.

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Somatic copy number gains in MYC, BCL2, and BCL6 identifies a subset of aggressive alternative-DH/TH DLBCL patients

Abstract

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