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3. EIF1AX and RAS mutations cooperate to drive thyroid tumorigenesis through ATF4 and c-MYC

Author

Krishnamoorthy, Gnana P, Davidson, Natalie R, Leach, Steven D, Zhao, Zhen, Lowe, Scott W, Lee, Gina, Landa, Iňigo, Nagarajah, James, Saqcena, Mahesh, Singh, Kamini, Wendel, Hans-Guido, Dogan, Snjezana, Tamarapu, Prasanna P, Blenis, John, Ghossein, Ronald A, Knauf, Jeffrey A, Rätsch, Gunnar, and Fagin, James A

Subjects
Rare Diseases, Genetics, Cancer, Aetiology, 2.1 Biological and endogenous factors, Activating Transcription Factor 4, Alternative Splicing, Animals, Apoptosis, Carcinogenesis, Cell Proliferation, Eukaryotic Initiation Factor-1, Female, Gene Expression Regulation, Neoplastic, Humans, Mice, Mice, Inbred NOD, Mice, SCID, Mutation, Phosphorylation, Protein Biosynthesis, Protein Kinase Inhibitors, TOR Serine-Threonine Kinases, Thyroid Neoplasms, Tumor Cells, Cultured, Xenograft Model Antitumor Assays, ras Proteins, Oncology and Carcinogenesis
Abstract

Translation initiation is orchestrated by the cap binding and 43S preinitiation complexes (PIC). Eukaryotic initiation factor 1A (EIF1A) is essential for recruitment of the ternary complex and for assembling the 43S PIC. Recurrent EIF1AX mutations in papillary thyroid cancers are mutually exclusive with other drivers, including RAS. EIF1AX mutations are enriched in advanced thyroid cancers, where they display a striking co-occurrence with RAS, which cooperates to induce tumorigenesis in mice and isogenic cell lines. The C-terminal EIF1AX-A113splice mutation is the most prevalent in advanced thyroid cancer. EIF1AX-A113splice variants stabilize the PIC and induce ATF4, a sensor of cellular stress, which is co-opted to suppress EIF2α phosphorylation, enabling a general increase in protein synthesis. RAS stabilizes c-MYC, an effect augmented by EIF1AX-A113splice. ATF4 and c-MYC induce expression of amino acid transporters and enhance sensitivity of mTOR to amino acid supply. These mutually reinforcing events generate therapeutic vulnerabilities to MEK, BRD4, and mTOR kinase inhibitors. SIGNIFICANCE: Mutations of EIF1AX, a component of the translation PIC, co-occur with RAS in advanced thyroid cancers and promote tumorigenesis. EIF1AX-A113splice drives an ATF4-induced dephosphorylation of EIF2α, resulting in increased protein synthesis. ATF4 also cooperates with c-MYC to sensitize mTOR to amino acid supply, thus generating vulnerability to mTOR kinase inhibitors. This article is highlighted in the In This Issue feature, p. 151.

Published
2019

5. CREBBP Inactivation Promotes the Development of HDAC3-Dependent Lymphomas

Author

Jiang, Yanwen, Ortega-Molina, Ana, Geng, Huimin, Ying, Hsia-Yuan, Hatzi, Katerina, Parsa, Sara, McNally, Dylan, Wang, Ling, Doane, Ashley S, Agirre, Xabier, Teater, Matt, Meydan, Cem, Li, Zhuoning, Poloway, David, Wang, Shenqiu, Ennishi, Daisuke, Scott, David W, Stengel, Kristy R, Kranz, Janice E, Holson, Edward, Sharma, Sneh, Young, James W, Chu, Chi-Shuen, Roeder, Robert G, Shaknovich, Rita, Hiebert, Scott W, Gascoyne, Randy D, Tam, Wayne, Elemento, Olivier, Wendel, Hans-Guido, and Melnick, Ari M

Subjects
Hematology, Rare Diseases, Lymphoma, Genetics, Clinical Research, Cancer, Biotechnology, Aetiology, 2.1 Biological and endogenous factors, Acetylation, Animals, CREB-Binding Protein, Cell Line, Tumor, Enhancer Elements, Genetic, Gene Knockout Techniques, Germinal Center, Histone Deacetylases, Histones, Humans, Lymphoma, Large B-Cell, Diffuse, Mice, Mutation, Neoplasm Transplantation, Nuclear Receptor Co-Repressor 2, Proto-Oncogene Proteins c-bcl-6, Transcription, Genetic, Oncology and Carcinogenesis
Abstract

Somatic mutations in CREBBP occur frequently in B-cell lymphoma. Here, we show that loss of CREBBP facilitates the development of germinal center (GC)-derived lymphomas in mice. In both human and murine lymphomas, CREBBP loss-of-function resulted in focal depletion of enhancer H3K27 acetylation and aberrant transcriptional silencing of genes that regulate B-cell signaling and immune responses, including class II MHC. Mechanistically, CREBBP-regulated enhancers are counter-regulated by the BCL6 transcriptional repressor in a complex with SMRT and HDAC3, which we found to bind extensively to MHC class II loci. HDAC3 loss-of-function rescued repression of these enhancers and corresponding genes, including MHC class II, and more profoundly suppressed CREBBP-mutant lymphomas in vitro and in vivo Hence, CREBBP loss-of-function contributes to lymphomagenesis by enabling unopposed suppression of enhancers by BCL6/SMRT/HDAC3 complexes, suggesting HDAC3-targeted therapy as a precision approach for CREBBP-mutant lymphomas.SignificanceOur findings establish the tumor suppressor function of CREBBP in GC lymphomas in which CREBBP mutations disable acetylation and result in unopposed deacetylation by BCL6/SMRT/HDAC3 complexes at enhancers of B-cell signaling and immune response genes. Hence, inhibition of HDAC3 can restore the enhancer histone acetylation and may serve as a targeted therapy for CREBBP-mutant lymphomas. Cancer Discov; 7(1); 38-53. ©2016 AACR.See related commentary by Höpken, p. 14This article is highlighted in the In This Issue feature, p. 1.

Published
2017

6. The serine hydroxymethyltransferase-2 (SHMT2) initiates lymphoma development through epigenetic tumor suppressor silencing

Author

Parsa, Sara, Ortega-Molina, Ana, Ying, Hsia-Yuan, Jiang, Man, Teater, Matt, Wang, Jiahui, Zhao, Chunying, Reznik, Ed, Pasion, Joyce P., Kuo, David, Mohan, Prathibha, Wang, Shenqiu, Camarillo, Jeannie M., Thomas, Paul M., Jain, Neeraj, Garcia-Bermudez, Javier, Cho, Byoung-kyu, Tam, Wayne, Kelleher, Neil L., Socci, Nicholas, Dogan, Ahmet, De Stanchina, Elisa, Ciriello, Giovanni, Green, Michael R., Li, Sheng, Birsoy, Kivanc, Melnick, Ari M., and Wendel, Hans-Guido

Published
2020
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9. O-GlcNAcase targets pyruvate kinase M2 to regulate tumor growth

Author

Singh, Jay Prakash, Qian, Kevin, Lee, Jeong-Sang, Zhou, Jinfeng, Han, Xuemei, Zhang, Bichen, Ong, Qunxiang, Ni, Weiming, Jiang, Mingzuo, Ruan, Hai-Bin, Li, Min-Dian, Zhang, Kaisi, Ding, Zhaobing, Lee, Philip, Singh, Kamini, Wu, Jing, Herzog, Raimund I., Kaech, Susan, Wendel, Hans-Guido, Yates, III, John R., Han, Weiping, Sherwin, Robert S., Nie, Yongzhan, and Yang, Xiaoyong

Published
2020
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12. Small Cell Lung Cancer: Can Recent Advances in Biology and Molecular Biology Be Translated into Improved Outcomes?

Author

Bunn, Paul A., Jr., Minna, John D., Augustyn, Alexander, Gazdar, Adi F., Ouadah, Youcef, Krasnow, Mark A., Berns, Anton, Brambilla, Elisabeth, Rekhtman, Natasha, Massion, Pierre P., Niederst, Matthew, Peifer, Martin, Yokota, Jun, Govindan, Ramaswamy, Poirier, John T., Byers, Lauren A., Wynes, Murry W., McFadden, David G., MacPherson, David, Hann, Christine L., Farago, Anna F., Dive, Caroline, Teicher, Beverly A., Peacock, Craig D., Johnson, Jane E., Cobb, Melanie H., Wendel, Hans-Guido, Spigel, David, Sage, Julien, Yang, Ping, Pietanza, M. Catherine, Krug, Lee M., Heymach, John, Ujhazy, Peter, Zhou, Caicun, Goto, Koichi, Dowlati, Afshin, Christensen, Camilla Laulund, Park, Keunchil, Einhorn, Lawrence H., Edelman, Martin J., Giaccone, Giuseppe, Gerber, David E., Salgia, Ravi, Owonikoko, Taofeek, Malik, Shakun, Karachaliou, Niki, Gandara, David R., Slotman, Ben J., Blackhall, Fiona, Goss, Glenwood, Thomas, Roman, Rudin, Charles M., and Hirsch, Fred R.

Published
2016
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13. Data from EIF1AX and RAS Mutations Cooperate to Drive Thyroid Tumorigenesis through ATF4 and c-MYC

Author

Krishnamoorthy, Gnana P., primary, Davidson, Natalie R., primary, Leach, Steven D., primary, Zhao, Zhen, primary, Lowe, Scott W., primary, Lee, Gina, primary, Landa, Iňigo, primary, Nagarajah, James, primary, Saqcena, Mahesh, primary, Singh, Kamini, primary, Wendel, Hans-Guido, primary, Dogan, Snjezana, primary, Tamarapu, Prasanna P., primary, Blenis, John, primary, Ghossein, Ronald A., primary, Knauf, Jeffrey A., primary, Rätsch, Gunnar, primary, and Fagin, James A., primary

Published
2023
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14. Supplementary Figures and Data from Identification of Novel Therapeutic Targets for Fibrolamellar Carcinoma Using Patient-Derived Xenografts and Direct-from-Patient Screening

Author

Lalazar, Gadi, primary, Requena, David, primary, Ramos-Espiritu, Lavoisier, primary, Ng, Denise, primary, Bhola, Patrick D., primary, de Jong, Ype P., primary, Wang, Ruisi, primary, Narayan, Nicole J.C., primary, Shebl, Bassem, primary, Levin, Solomon, primary, Michailidis, Eleftherios, primary, Kabbani, Mohammad, primary, Vercauteren, Koen O.A., primary, Hurley, Arlene M., primary, Farber, Benjamin A., primary, Hammond, William J., primary, Saltsman, James A., primary, Weinberg, Ethan M., primary, Glickman, J. Fraser, primary, Lyons, Barbara A., primary, Ellison, Jessica, primary, Schadde, Erik, primary, Hertl, Martin, primary, Leiting, Jennifer L., primary, Truty, Mark J., primary, Smoot, Rory L., primary, Tierney, Faith, primary, Kato, Tomoaki, primary, Wendel, Hans-Guido, primary, LaQuaglia, Michael P., primary, Rice, Charles M., primary, Letai, Anthony, primary, Coffino, Philip, primary, Torbenson, Michael S., primary, Ortiz, Michael V., primary, and Simon, Sanford M., primary

Published
2023
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15. Supplementary Table S5 from CREBBP Inactivation Promotes the Development of HDAC3-Dependent Lymphomas

Author

Jiang, Yanwen, primary, Ortega-Molina, Ana, primary, Geng, Huimin, primary, Ying, Hsia-Yuan, primary, Hatzi, Katerina, primary, Parsa, Sara, primary, McNally, Dylan, primary, Wang, Ling, primary, Doane, Ashley S., primary, Agirre, Xabier, primary, Teater, Matt, primary, Meydan, Cem, primary, Li, Zhuoning, primary, Poloway, David, primary, Wang, Shenqiu, primary, Ennishi, Daisuke, primary, Scott, David W., primary, Stengel, Kristy R., primary, Kranz, Janice E., primary, Holson, Edward, primary, Sharma, Sneh, primary, Young, James W., primary, Chu, Chi-Shuen, primary, Roeder, Robert G., primary, Shaknovich, Rita, primary, Hiebert, Scott W., primary, Gascoyne, Randy D., primary, Tam, Wayne, primary, Elemento, Olivier, primary, Wendel, Hans-Guido, primary, and Melnick, Ari M., primary

Published
2023
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16. Supplementary Data from EIF1AX and RAS Mutations Cooperate to Drive Thyroid Tumorigenesis through ATF4 and c-MYC

Author

Krishnamoorthy, Gnana P., primary, Davidson, Natalie R., primary, Leach, Steven D., primary, Zhao, Zhen, primary, Lowe, Scott W., primary, Lee, Gina, primary, Landa, Iňigo, primary, Nagarajah, James, primary, Saqcena, Mahesh, primary, Singh, Kamini, primary, Wendel, Hans-Guido, primary, Dogan, Snjezana, primary, Tamarapu, Prasanna P., primary, Blenis, John, primary, Ghossein, Ronald A., primary, Knauf, Jeffrey A., primary, Rätsch, Gunnar, primary, and Fagin, James A., primary

Published
2023
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17. Supplementary Table 3 from Identification of Novel Therapeutic Targets for Fibrolamellar Carcinoma Using Patient-Derived Xenografts and Direct-from-Patient Screening

Author

Lalazar, Gadi, primary, Requena, David, primary, Ramos-Espiritu, Lavoisier, primary, Ng, Denise, primary, Bhola, Patrick D., primary, de Jong, Ype P., primary, Wang, Ruisi, primary, Narayan, Nicole J.C., primary, Shebl, Bassem, primary, Levin, Solomon, primary, Michailidis, Eleftherios, primary, Kabbani, Mohammad, primary, Vercauteren, Koen O.A., primary, Hurley, Arlene M., primary, Farber, Benjamin A., primary, Hammond, William J., primary, Saltsman, James A., primary, Weinberg, Ethan M., primary, Glickman, J. Fraser, primary, Lyons, Barbara A., primary, Ellison, Jessica, primary, Schadde, Erik, primary, Hertl, Martin, primary, Leiting, Jennifer L., primary, Truty, Mark J., primary, Smoot, Rory L., primary, Tierney, Faith, primary, Kato, Tomoaki, primary, Wendel, Hans-Guido, primary, LaQuaglia, Michael P., primary, Rice, Charles M., primary, Letai, Anthony, primary, Coffino, Philip, primary, Torbenson, Michael S., primary, Ortiz, Michael V., primary, and Simon, Sanford M., primary

Published
2023
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18. Supplementary Table S3 from EIF1AX and RAS Mutations Cooperate to Drive Thyroid Tumorigenesis through ATF4 and c-MYC

Author

Krishnamoorthy, Gnana P., primary, Davidson, Natalie R., primary, Leach, Steven D., primary, Zhao, Zhen, primary, Lowe, Scott W., primary, Lee, Gina, primary, Landa, Iňigo, primary, Nagarajah, James, primary, Saqcena, Mahesh, primary, Singh, Kamini, primary, Wendel, Hans-Guido, primary, Dogan, Snjezana, primary, Tamarapu, Prasanna P., primary, Blenis, John, primary, Ghossein, Ronald A., primary, Knauf, Jeffrey A., primary, Rätsch, Gunnar, primary, and Fagin, James A., primary

Published
2023
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19. Data from Identification of Novel Therapeutic Targets for Fibrolamellar Carcinoma Using Patient-Derived Xenografts and Direct-from-Patient Screening

Author

Lalazar, Gadi, primary, Requena, David, primary, Ramos-Espiritu, Lavoisier, primary, Ng, Denise, primary, Bhola, Patrick D., primary, de Jong, Ype P., primary, Wang, Ruisi, primary, Narayan, Nicole J.C., primary, Shebl, Bassem, primary, Levin, Solomon, primary, Michailidis, Eleftherios, primary, Kabbani, Mohammad, primary, Vercauteren, Koen O.A., primary, Hurley, Arlene M., primary, Farber, Benjamin A., primary, Hammond, William J., primary, Saltsman, James A., primary, Weinberg, Ethan M., primary, Glickman, J. Fraser, primary, Lyons, Barbara A., primary, Ellison, Jessica, primary, Schadde, Erik, primary, Hertl, Martin, primary, Leiting, Jennifer L., primary, Truty, Mark J., primary, Smoot, Rory L., primary, Tierney, Faith, primary, Kato, Tomoaki, primary, Wendel, Hans-Guido, primary, LaQuaglia, Michael P., primary, Rice, Charles M., primary, Letai, Anthony, primary, Coffino, Philip, primary, Torbenson, Michael S., primary, Ortiz, Michael V., primary, and Simon, Sanford M., primary

Published
2023
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20. Data from CREBBP Inactivation Promotes the Development of HDAC3-Dependent Lymphomas

Author

Jiang, Yanwen, primary, Ortega-Molina, Ana, primary, Geng, Huimin, primary, Ying, Hsia-Yuan, primary, Hatzi, Katerina, primary, Parsa, Sara, primary, McNally, Dylan, primary, Wang, Ling, primary, Doane, Ashley S., primary, Agirre, Xabier, primary, Teater, Matt, primary, Meydan, Cem, primary, Li, Zhuoning, primary, Poloway, David, primary, Wang, Shenqiu, primary, Ennishi, Daisuke, primary, Scott, David W., primary, Stengel, Kristy R., primary, Kranz, Janice E., primary, Holson, Edward, primary, Sharma, Sneh, primary, Young, James W., primary, Chu, Chi-Shuen, primary, Roeder, Robert G., primary, Shaknovich, Rita, primary, Hiebert, Scott W., primary, Gascoyne, Randy D., primary, Tam, Wayne, primary, Elemento, Olivier, primary, Wendel, Hans-Guido, primary, and Melnick, Ari M., primary

Published
2023
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21. Data from Clinical and Biological Correlates of Neurotoxicity Associated with CAR T-cell Therapy in Patients with B-cell Acute Lymphoblastic Leukemia

Author

Santomasso, Bianca D., primary, Park, Jae H., primary, Salloum, Darin, primary, Riviere, Isabelle, primary, Flynn, Jessica, primary, Mead, Elena, primary, Halton, Elizabeth, primary, Wang, Xiuyan, primary, Senechal, Brigitte, primary, Purdon, Terence, primary, Cross, Justin R., primary, Liu, Hui, primary, Vachha, Behroze, primary, Chen, Xi, primary, DeAngelis, Lisa M., primary, Li, Daniel, primary, Bernal, Yvette, primary, Gonen, Mithat, primary, Wendel, Hans-Guido, primary, Sadelain, Michel, primary, and Brentjens, Renier J., primary

Published
2023
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22. Figure S1, Figure S2, Figure S3, Figure S4 from Clinical and Biological Correlates of Neurotoxicity Associated with CAR T-cell Therapy in Patients with B-cell Acute Lymphoblastic Leukemia

Author

Santomasso, Bianca D., primary, Park, Jae H., primary, Salloum, Darin, primary, Riviere, Isabelle, primary, Flynn, Jessica, primary, Mead, Elena, primary, Halton, Elizabeth, primary, Wang, Xiuyan, primary, Senechal, Brigitte, primary, Purdon, Terence, primary, Cross, Justin R., primary, Liu, Hui, primary, Vachha, Behroze, primary, Chen, Xi, primary, DeAngelis, Lisa M., primary, Li, Daniel, primary, Bernal, Yvette, primary, Gonen, Mithat, primary, Wendel, Hans-Guido, primary, Sadelain, Michel, primary, and Brentjens, Renier J., primary

Published
2023
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23. Supplementary Figures S1 - S14 from CREBBP Inactivation Promotes the Development of HDAC3-Dependent Lymphomas

Author

Jiang, Yanwen, primary, Ortega-Molina, Ana, primary, Geng, Huimin, primary, Ying, Hsia-Yuan, primary, Hatzi, Katerina, primary, Parsa, Sara, primary, McNally, Dylan, primary, Wang, Ling, primary, Doane, Ashley S., primary, Agirre, Xabier, primary, Teater, Matt, primary, Meydan, Cem, primary, Li, Zhuoning, primary, Poloway, David, primary, Wang, Shenqiu, primary, Ennishi, Daisuke, primary, Scott, David W., primary, Stengel, Kristy R., primary, Kranz, Janice E., primary, Holson, Edward, primary, Sharma, Sneh, primary, Young, James W., primary, Chu, Chi-Shuen, primary, Roeder, Robert G., primary, Shaknovich, Rita, primary, Hiebert, Scott W., primary, Gascoyne, Randy D., primary, Tam, Wayne, primary, Elemento, Olivier, primary, Wendel, Hans-Guido, primary, and Melnick, Ari M., primary

Published
2023
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24. Table S1, Table S2, Table S3, Table S4 from Clinical and Biological Correlates of Neurotoxicity Associated with CAR T-cell Therapy in Patients with B-cell Acute Lymphoblastic Leukemia

Author

Santomasso, Bianca D., primary, Park, Jae H., primary, Salloum, Darin, primary, Riviere, Isabelle, primary, Flynn, Jessica, primary, Mead, Elena, primary, Halton, Elizabeth, primary, Wang, Xiuyan, primary, Senechal, Brigitte, primary, Purdon, Terence, primary, Cross, Justin R., primary, Liu, Hui, primary, Vachha, Behroze, primary, Chen, Xi, primary, DeAngelis, Lisa M., primary, Li, Daniel, primary, Bernal, Yvette, primary, Gonen, Mithat, primary, Wendel, Hans-Guido, primary, Sadelain, Michel, primary, and Brentjens, Renier J., primary

Published
2023
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25. Supplementary Table 4 from Targeting eIF4A-Dependent Translation of KRAS Signaling Molecules

Author

Singh, Kamini, primary, Lin, Jianan, primary, Lecomte, Nicolas, primary, Mohan, Prathibha, primary, Gokce, Askan, primary, Sanghvi, Viraj R., primary, Jiang, Man, primary, Grbovic-Huezo, Olivera, primary, Burčul, Antonija, primary, Stark, Stefan G., primary, Romesser, Paul B., primary, Chang, Qing, primary, Melchor, Jerry P., primary, Beyer, Rachel K., primary, Duggan, Mark, primary, Fukase, Yoshiyuki, primary, Yang, Guangli, primary, Ouerfelli, Ouathek, primary, Viale, Agnes, primary, de Stanchina, Elisa, primary, Stamford, Andrew W., primary, Meinke, Peter T., primary, Rätsch, Gunnar, primary, Leach, Steven D., primary, Ouyang, Zhengqing, primary, and Wendel, Hans-Guido, primary

Published
2023
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26. Supplementary Table 2 from Targeting eIF4A-Dependent Translation of KRAS Signaling Molecules

Author

Singh, Kamini, primary, Lin, Jianan, primary, Lecomte, Nicolas, primary, Mohan, Prathibha, primary, Gokce, Askan, primary, Sanghvi, Viraj R., primary, Jiang, Man, primary, Grbovic-Huezo, Olivera, primary, Burčul, Antonija, primary, Stark, Stefan G., primary, Romesser, Paul B., primary, Chang, Qing, primary, Melchor, Jerry P., primary, Beyer, Rachel K., primary, Duggan, Mark, primary, Fukase, Yoshiyuki, primary, Yang, Guangli, primary, Ouerfelli, Ouathek, primary, Viale, Agnes, primary, de Stanchina, Elisa, primary, Stamford, Andrew W., primary, Meinke, Peter T., primary, Rätsch, Gunnar, primary, Leach, Steven D., primary, Ouyang, Zhengqing, primary, and Wendel, Hans-Guido, primary

Published
2023
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27. Supplementary figure S4 from Targeting eIF4A-Dependent Translation of KRAS Signaling Molecules

Author

Singh, Kamini, primary, Lin, Jianan, primary, Lecomte, Nicolas, primary, Mohan, Prathibha, primary, Gokce, Askan, primary, Sanghvi, Viraj R., primary, Jiang, Man, primary, Grbovic-Huezo, Olivera, primary, Burčul, Antonija, primary, Stark, Stefan G., primary, Romesser, Paul B., primary, Chang, Qing, primary, Melchor, Jerry P., primary, Beyer, Rachel K., primary, Duggan, Mark, primary, Fukase, Yoshiyuki, primary, Yang, Guangli, primary, Ouerfelli, Ouathek, primary, Viale, Agnes, primary, de Stanchina, Elisa, primary, Stamford, Andrew W., primary, Meinke, Peter T., primary, Rätsch, Gunnar, primary, Leach, Steven D., primary, Ouyang, Zhengqing, primary, and Wendel, Hans-Guido, primary

Published
2023
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28. Supplementary Table 1 from Targeting eIF4A-Dependent Translation of KRAS Signaling Molecules

Author

Singh, Kamini, primary, Lin, Jianan, primary, Lecomte, Nicolas, primary, Mohan, Prathibha, primary, Gokce, Askan, primary, Sanghvi, Viraj R., primary, Jiang, Man, primary, Grbovic-Huezo, Olivera, primary, Burčul, Antonija, primary, Stark, Stefan G., primary, Romesser, Paul B., primary, Chang, Qing, primary, Melchor, Jerry P., primary, Beyer, Rachel K., primary, Duggan, Mark, primary, Fukase, Yoshiyuki, primary, Yang, Guangli, primary, Ouerfelli, Ouathek, primary, Viale, Agnes, primary, de Stanchina, Elisa, primary, Stamford, Andrew W., primary, Meinke, Peter T., primary, Rätsch, Gunnar, primary, Leach, Steven D., primary, Ouyang, Zhengqing, primary, and Wendel, Hans-Guido, primary

Published
2023
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29. Supplementary Table 3 from Targeting eIF4A-Dependent Translation of KRAS Signaling Molecules

Author

Singh, Kamini, primary, Lin, Jianan, primary, Lecomte, Nicolas, primary, Mohan, Prathibha, primary, Gokce, Askan, primary, Sanghvi, Viraj R., primary, Jiang, Man, primary, Grbovic-Huezo, Olivera, primary, Burčul, Antonija, primary, Stark, Stefan G., primary, Romesser, Paul B., primary, Chang, Qing, primary, Melchor, Jerry P., primary, Beyer, Rachel K., primary, Duggan, Mark, primary, Fukase, Yoshiyuki, primary, Yang, Guangli, primary, Ouerfelli, Ouathek, primary, Viale, Agnes, primary, de Stanchina, Elisa, primary, Stamford, Andrew W., primary, Meinke, Peter T., primary, Rätsch, Gunnar, primary, Leach, Steven D., primary, Ouyang, Zhengqing, primary, and Wendel, Hans-Guido, primary

Published
2023
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32. The H3K27me3 demethylase UTX is a gender-specific tumor suppressor in T-cell acute lymphoblastic leukemia

Author

Van der Meulen, Joni, Sanghvi, Viraj, Mavrakis, Konstantinos, Durinck, Kaat, Fang, Fang, Matthijssens, Filip, Rondou, Pieter, Rosen, Monica, Pieters, Tim, Vandenberghe, Peter, Delabesse, Eric, Lammens, Tim, De Moerloose, Barbara, Menten, Björn, Van Roy, Nadine, Verhasselt, Bruno, Poppe, Bruce, Benoit, Yves, Taghon, Tom, Melnick, Ari M., Speleman, Frank, Wendel, Hans-Guido, and Van Vlierberghe, Pieter

Published
2015
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34. TPX2 as Key Downstream Target of the eIF4A Controlled Translational Program in MYCN Driven Neuroblastoma

Author

Nunes, Carolina, primary, Bekaert, Sarah-Lee, additional, Parsa, Sara, additional, Nelen, Iris, additional, Martens, Fien, additional, T’sas, Sara, additional, Zhao, Peihua, additional, De Vloed, Fanny, additional, Eggermont, Aline, additional, Goosssens, Steven, additional, Sablina, Anna, additional, Wendel, Hans-Guido, additional, and Durinck, Kaat, additional

Published
2023
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39. The histone lysine methyltransferase KMT2D sustains a gene expression program that represses B cell lymphoma development

Author

Ortega-Molina, Ana, Boss, Isaac W., Canela, Andres, Pan, Heng, Jiang, Yanwen, Zhao, Chunying, Jiang, Man, Hu, Deqing, Agirre, Xabier, Niesvizky, Itamar, Lee, Ji-Eun, Chen, Hua-Tang, Ennishi, Daisuke, Scott, David W., Mottok, Anja, Hother, Christoffer, Liu, Shichong, Cao, Xing-Jun, Tam, Wayne, Shaknovich, Rita, Garcia, Benjamin A., Gascoyne, Randy D., Ge, Kai, Shilatifard, Ali, Elemento, Olivier, Nussenzweig, Andre, Melnick, Ari M., and Wendel, Hans-Guido

Subjects
Analysis, Research, Genetic aspects, Risk factors, Non-Hodgkin lymphomas -- Genetic aspects -- Research -- Risk factors, Cancer genetics -- Research, Gene expression -- Analysis, Non-Hodgkin's lymphomas -- Genetic aspects -- Research -- Risk factors, Cancer -- Genetic aspects
Abstract

A majority of B cell lymphomas-including follicular lymphoma (FL) and diffuse large B cell lymphoma (DLBCL), the most common forms of non-Hodgkin lymphoma-arise from germinal center (GC) B cells. GCs [...], The gene encoding the lysine-specific histone methyltransferase KMT2D has emerged as one of the most frequently mutated genes in follicular lymphoma and diffuse large B cell lymphoma; however, the biological consequences of KMT2D mutations on lymphoma development are not known. Here we show that KMT2D functions as a bona fide tumor suppressor and that its genetic ablation in B cells promotes lymphoma development in mice. KMT2D deficiency also delays germinal center involution and impedes B cell differentiation and class switch recombination. Integrative genomic analyses indicate that KMT2D affects methylation of lysine 4 on histone H3 (H3K4) and expression of a set of genes, including those in the CD40, JAK-STAT, Toll-like receptor and B cell receptor signaling pathways. Notably, other KMT2D target genes include frequently mutated tumor suppressor genes such as TNFAIP3, SOCS3 and TNFRSF14. Therefore, KMT2D mutations may promote malignant outgrowth by perturbing the expression of tumor suppressor genes that control B cell-activating pathways.

Published
2015
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40. Transcriptional and Translational Dynamics of Zika and Dengue Virus Infection

Author

Singh, Kamini, primary, Martinez, Maria Guadalupe, additional, Lin, Jianan, additional, Gregory, James, additional, Nguyen, Trang Uyen, additional, Abdelaal, Rawan, additional, Kang, Kristy, additional, Brennand, Kristen, additional, Grünweller, Arnold, additional, Ouyang, Zhengqing, additional, Phatnani, Hemali, additional, Kielian, Margaret, additional, and Wendel, Hans-Guido, additional

Published
2022
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46. The Eph-Receptor A7 Is a Soluble Tumor Suppressor for Follicular Lymphoma

Author

Oricchio, Elisa, Nanjangud, Gouri, Wolfe, Andrew L., Schatz, Jonathan H., Mavrakis, Konstantinos J., Jiang, Man, Liu, Xiaoping, Bruno, Joanne, Heguy, Adriana, Olshen, Adam B., Socci, Nicholas D., Teruya-Feldstein, Julie, Weis-Garcia, Frances, Tam, Wayne, Shaknovich, Rita, Melnick, Ari, Himanen, Juha P., Chaganti, R.S.K., and Wendel, Hans-Guido

Published
2011
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48. Rocaglates as Antivirals: Comparing the Effects on Viral Resistance, Anti-Coronaviral Activity, RNA-Clamping on eIF4A and Immune Cell Toxicity

Author

Obermann, Wiebke, primary, Friedrich, Alexandra, additional, Madhugiri, Ramakanth, additional, Klemm, Paul, additional, Mengel, Jan Philipp, additional, Hain, Torsten, additional, Pleschka, Stephan, additional, Wendel, Hans-Guido, additional, Hartmann, Roland K., additional, Schiffmann, Susanne, additional, Ziebuhr, John, additional, Müller, Christin, additional, and Grünweller, Arnold, additional

Published
2022
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