Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics

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Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics. / Schmitz, Roland; Young, Ryan M; Ceribelli, Michele; Jhavar, Sameer; Xiao, Wenming; Zhang, Meili; Wright, George; Shaffer, Arthur L; Hodson, Daniel J; Buras, Eric; Liu, Xuelu; Powell, John; Yang, Yandan; Xu, Weihong; Zhao, Hong; Kohlhammer, Holger; Rosenwald, Andreas; Kluin, Philip; Müller-Hermelink, Hans Konrad; Ott, German; Gascoyne, Randy D; Connors, Joseph M; Rimsza, Lisa M; Campo, Elias; Jaffe, Elaine S; Delabie, Jan; Smeland, Erlend B; Ogwang, Martin D; Reynolds, Steven J; Fisher, Richard I; Braziel, Rita M; Tubbs, Raymond R; Cook, James R; Weisenburger, Dennis D; Chan, Wing C; Pittaluga, Stefania; Wilson, Wyndham; Waldmann, Thomas A; Rowe, Martin; Mbulaiteye, Sam M; Rickinson, Alan B; Staudt, Louis M.

In: Nature, Vol. 490, No. 7418, 04.10.2012, p. 116-20.

Research output: Contribution to journalArticle

Harvard

Schmitz, R, Young, RM, Ceribelli, M, Jhavar, S, Xiao, W, Zhang, M, Wright, G, Shaffer, AL, Hodson, DJ, Buras, E, Liu, X, Powell, J, Yang, Y, Xu, W, Zhao, H, Kohlhammer, H, Rosenwald, A, Kluin, P, Müller-Hermelink, HK, Ott, G, Gascoyne, RD, Connors, JM, Rimsza, LM, Campo, E, Jaffe, ES, Delabie, J, Smeland, EB, Ogwang, MD, Reynolds, SJ, Fisher, RI, Braziel, RM, Tubbs, RR, Cook, JR, Weisenburger, DD, Chan, WC, Pittaluga, S, Wilson, W, Waldmann, TA, Rowe, M, Mbulaiteye, SM, Rickinson, AB & Staudt, LM 2012, 'Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics', Nature, vol. 490, no. 7418, pp. 116-20. https://doi.org/10.1038/nature11378

APA

Schmitz, R., Young, R. M., Ceribelli, M., Jhavar, S., Xiao, W., Zhang, M., Wright, G., Shaffer, A. L., Hodson, D. J., Buras, E., Liu, X., Powell, J., Yang, Y., Xu, W., Zhao, H., Kohlhammer, H., Rosenwald, A., Kluin, P., Müller-Hermelink, H. K., ... Staudt, L. M. (2012). Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics. Nature, 490(7418), 116-20. https://doi.org/10.1038/nature11378

Vancouver

Schmitz R, Young RM, Ceribelli M, Jhavar S, Xiao W, Zhang M et al. Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics. Nature. 2012 Oct 4;490(7418):116-20. https://doi.org/10.1038/nature11378

Author

Schmitz, Roland ; Young, Ryan M ; Ceribelli, Michele ; Jhavar, Sameer ; Xiao, Wenming ; Zhang, Meili ; Wright, George ; Shaffer, Arthur L ; Hodson, Daniel J ; Buras, Eric ; Liu, Xuelu ; Powell, John ; Yang, Yandan ; Xu, Weihong ; Zhao, Hong ; Kohlhammer, Holger ; Rosenwald, Andreas ; Kluin, Philip ; Müller-Hermelink, Hans Konrad ; Ott, German ; Gascoyne, Randy D ; Connors, Joseph M ; Rimsza, Lisa M ; Campo, Elias ; Jaffe, Elaine S ; Delabie, Jan ; Smeland, Erlend B ; Ogwang, Martin D ; Reynolds, Steven J ; Fisher, Richard I ; Braziel, Rita M ; Tubbs, Raymond R ; Cook, James R ; Weisenburger, Dennis D ; Chan, Wing C ; Pittaluga, Stefania ; Wilson, Wyndham ; Waldmann, Thomas A ; Rowe, Martin ; Mbulaiteye, Sam M ; Rickinson, Alan B ; Staudt, Louis M. / Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics. In: Nature. 2012 ; Vol. 490, No. 7418. pp. 116-20.

Bibtex

@article{1891b90444bc4e618cfade09fd3a7718,
title = "Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics",
abstract = "Burkitt's lymphoma (BL) can often be cured by intensive chemotherapy, but the toxicity of such therapy precludes its use in the elderly and in patients with endemic BL in developing countries, necessitating new strategies. The normal germinal centre B cell is the presumed cell of origin for both BL and diffuse large B-cell lymphoma (DLBCL), yet gene expression analysis suggests that these malignancies may use different oncogenic pathways. BL is subdivided into a sporadic subtype that is diagnosed in developed countries, the Epstein-Barr-virus-associated endemic subtype, and an HIV-associated subtype, but it is unclear whether these subtypes use similar or divergent oncogenic mechanisms. Here we used high-throughput RNA sequencing and RNA interference screening to discover essential regulatory pathways in BL that cooperate with MYC, the defining oncogene of this cancer. In 70% of sporadic BL cases, mutations affecting the transcription factor TCF3 (E2A) or its negative regulator ID3 fostered TCF3 dependency. TCF3 activated the pro-survival phosphatidylinositol-3-OH kinase pathway in BL, in part by augmenting tonic B-cell receptor signalling. In 38% of sporadic BL cases, oncogenic CCND3 mutations produced highly stable cyclin D3 isoforms that drive cell cycle progression. These findings suggest opportunities to improve therapy for patients with BL.",
author = "Roland Schmitz and Young, {Ryan M} and Michele Ceribelli and Sameer Jhavar and Wenming Xiao and Meili Zhang and George Wright and Shaffer, {Arthur L} and Hodson, {Daniel J} and Eric Buras and Xuelu Liu and John Powell and Yandan Yang and Weihong Xu and Hong Zhao and Holger Kohlhammer and Andreas Rosenwald and Philip Kluin and M{\"u}ller-Hermelink, {Hans Konrad} and German Ott and Gascoyne, {Randy D} and Connors, {Joseph M} and Rimsza, {Lisa M} and Elias Campo and Jaffe, {Elaine S} and Jan Delabie and Smeland, {Erlend B} and Ogwang, {Martin D} and Reynolds, {Steven J} and Fisher, {Richard I} and Braziel, {Rita M} and Tubbs, {Raymond R} and Cook, {James R} and Weisenburger, {Dennis D} and Chan, {Wing C} and Stefania Pittaluga and Wyndham Wilson and Waldmann, {Thomas A} and Martin Rowe and Mbulaiteye, {Sam M} and Rickinson, {Alan B} and Staudt, {Louis M}",
year = "2012",
month = oct,
day = "4",
doi = "10.1038/nature11378",
language = "English",
volume = "490",
pages = "116--20",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7418",

}

RIS

TY - JOUR

T1 - Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics

AU - Schmitz, Roland

AU - Young, Ryan M

AU - Ceribelli, Michele

AU - Jhavar, Sameer

AU - Xiao, Wenming

AU - Zhang, Meili

AU - Wright, George

AU - Shaffer, Arthur L

AU - Hodson, Daniel J

AU - Buras, Eric

AU - Liu, Xuelu

AU - Powell, John

AU - Yang, Yandan

AU - Xu, Weihong

AU - Zhao, Hong

AU - Kohlhammer, Holger

AU - Rosenwald, Andreas

AU - Kluin, Philip

AU - Müller-Hermelink, Hans Konrad

AU - Ott, German

AU - Gascoyne, Randy D

AU - Connors, Joseph M

AU - Rimsza, Lisa M

AU - Campo, Elias

AU - Jaffe, Elaine S

AU - Delabie, Jan

AU - Smeland, Erlend B

AU - Ogwang, Martin D

AU - Reynolds, Steven J

AU - Fisher, Richard I

AU - Braziel, Rita M

AU - Tubbs, Raymond R

AU - Cook, James R

AU - Weisenburger, Dennis D

AU - Chan, Wing C

AU - Pittaluga, Stefania

AU - Wilson, Wyndham

AU - Waldmann, Thomas A

AU - Rowe, Martin

AU - Mbulaiteye, Sam M

AU - Rickinson, Alan B

AU - Staudt, Louis M

PY - 2012/10/4

Y1 - 2012/10/4

N2 - Burkitt's lymphoma (BL) can often be cured by intensive chemotherapy, but the toxicity of such therapy precludes its use in the elderly and in patients with endemic BL in developing countries, necessitating new strategies. The normal germinal centre B cell is the presumed cell of origin for both BL and diffuse large B-cell lymphoma (DLBCL), yet gene expression analysis suggests that these malignancies may use different oncogenic pathways. BL is subdivided into a sporadic subtype that is diagnosed in developed countries, the Epstein-Barr-virus-associated endemic subtype, and an HIV-associated subtype, but it is unclear whether these subtypes use similar or divergent oncogenic mechanisms. Here we used high-throughput RNA sequencing and RNA interference screening to discover essential regulatory pathways in BL that cooperate with MYC, the defining oncogene of this cancer. In 70% of sporadic BL cases, mutations affecting the transcription factor TCF3 (E2A) or its negative regulator ID3 fostered TCF3 dependency. TCF3 activated the pro-survival phosphatidylinositol-3-OH kinase pathway in BL, in part by augmenting tonic B-cell receptor signalling. In 38% of sporadic BL cases, oncogenic CCND3 mutations produced highly stable cyclin D3 isoforms that drive cell cycle progression. These findings suggest opportunities to improve therapy for patients with BL.

AB - Burkitt's lymphoma (BL) can often be cured by intensive chemotherapy, but the toxicity of such therapy precludes its use in the elderly and in patients with endemic BL in developing countries, necessitating new strategies. The normal germinal centre B cell is the presumed cell of origin for both BL and diffuse large B-cell lymphoma (DLBCL), yet gene expression analysis suggests that these malignancies may use different oncogenic pathways. BL is subdivided into a sporadic subtype that is diagnosed in developed countries, the Epstein-Barr-virus-associated endemic subtype, and an HIV-associated subtype, but it is unclear whether these subtypes use similar or divergent oncogenic mechanisms. Here we used high-throughput RNA sequencing and RNA interference screening to discover essential regulatory pathways in BL that cooperate with MYC, the defining oncogene of this cancer. In 70% of sporadic BL cases, mutations affecting the transcription factor TCF3 (E2A) or its negative regulator ID3 fostered TCF3 dependency. TCF3 activated the pro-survival phosphatidylinositol-3-OH kinase pathway in BL, in part by augmenting tonic B-cell receptor signalling. In 38% of sporadic BL cases, oncogenic CCND3 mutations produced highly stable cyclin D3 isoforms that drive cell cycle progression. These findings suggest opportunities to improve therapy for patients with BL.

U2 - 10.1038/nature11378

DO - 10.1038/nature11378

M3 - Article

C2 - 22885699

VL - 490

SP - 116

EP - 120

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7418

ER -