Search

Your search keyword '"Rajagopalan, Deepthi"' showing total 19 results
Start Over Author "Rajagopalan, Deepthi"
19 results on '"Rajagopalan, Deepthi"'

1. Enteropathy-associated T cell lymphoma subtypes are characterized by loss of function of SETD2

Author

Moffitt, Andrea B, Ondrejka, Sarah L, McKinney, Matthew, Rempel, Rachel E, Goodlad, John R, Teh, Chun Huat, Leppa, Sirpa, Mannisto, Susanna, Kovanen, Panu E, Tse, Eric, Au-Yeung, Rex KH, Kwong, Yok-Lam, Srivastava, Gopesh, Iqbal, Javeed, Yu, Jiayu, Naresh, Kikkeri, Villa, Diego, Gascoyne, Randy D, Said, Jonathan, Czader, Magdalena B, Chadburn, Amy, Richards, Kristy L, Rajagopalan, Deepthi, Davis, Nicholas S, Smith, Eileen C, Palus, Brooke C, Tzeng, Tiffany J, Healy, Jane A, Lugar, Patricia L, Datta, Jyotishka, Love, Cassandra, Levy, Shawn, Dunson, David B, Zhuang, Yuan, Hsi, Eric D, and Dave, Sandeep S

Subjects
Genetics, Cancer, Hematology, Lymphoma, Rare Diseases, Clinical Research, Biotechnology, Digestive Diseases, 2.1 Biological and endogenous factors, Aetiology, Animals, DNA Copy Number Variations, Enteropathy-Associated T-Cell Lymphoma, Female, Gene Expression Profiling, Gene Silencing, Histone-Lysine N-Methyltransferase, Humans, Male, Mice, Knockout, Middle Aged, Mutation, Sequence Analysis, DNA, T-Lymphocytes, Medical and Health Sciences, Immunology
Abstract

Enteropathy-associated T cell lymphoma (EATL) is a lethal, and the most common, neoplastic complication of celiac disease. Here, we defined the genetic landscape of EATL through whole-exome sequencing of 69 EATL tumors. SETD2 was the most frequently silenced gene in EATL (32% of cases). The JAK-STAT pathway was the most frequently mutated pathway, with frequent mutations in STAT5B as well as JAK1, JAK3, STAT3, and SOCS1 We also identified mutations in KRAS, TP53, and TERT Type I EATL and type II EATL (monomorphic epitheliotropic intestinal T cell lymphoma) had highly overlapping genetic alterations indicating shared mechanisms underlying their pathogenesis. We modeled the effects of SETD2 loss in vivo by developing a T cell-specific knockout mouse. These mice manifested an expansion of γδ T cells, indicating novel roles for SETD2 in T cell development and lymphomagenesis. Our data render the most comprehensive genetic portrait yet of this uncommon but lethal disease and may inform future classification schemes.

Published
2017

2. Data from The Genetic Basis of Hepatosplenic T-cell Lymphoma

Author

McKinney, Matthew, primary, Moffitt, Andrea B., primary, Gaulard, Philippe, primary, Travert, Marion, primary, De Leval, Laurence, primary, Nicolae, Alina, primary, Raffeld, Mark, primary, Jaffe, Elaine S., primary, Pittaluga, Stefania, primary, Xi, Liqiang, primary, Heavican, Tayla, primary, Iqbal, Javeed, primary, Belhadj, Karim, primary, Delfau-Larue, Marie Helene, primary, Fataccioli, Virginie, primary, Czader, Magdalena B., primary, Lossos, Izidore S., primary, Chapman-Fredricks, Jennifer R., primary, Richards, Kristy L., primary, Fedoriw, Yuri, primary, Ondrejka, Sarah L., primary, Hsi, Eric D., primary, Low, Lawrence, primary, Weisenburger, Dennis, primary, Chan, Wing C., primary, Mehta-Shah, Neha, primary, Horwitz, Steven, primary, Bernal-Mizrachi, Leon, primary, Flowers, Christopher R., primary, Beaven, Anne W., primary, Parihar, Mayur, primary, Baseggio, Lucile, primary, Parrens, Marie, primary, Moreau, Anne, primary, Sujobert, Pierre, primary, Pilichowska, Monika, primary, Evens, Andrew M., primary, Chadburn, Amy, primary, Au-Yeung, Rex K.H., primary, Srivastava, Gopesh, primary, Choi, William W. L., primary, Goodlad, John R., primary, Aurer, Igor, primary, Basic-Kinda, Sandra, primary, Gascoyne, Randy D., primary, Davis, Nicholas S., primary, Li, Guojie, primary, Zhang, Jenny, primary, Rajagopalan, Deepthi, primary, Reddy, Anupama, primary, Love, Cassandra, primary, Levy, Shawn, primary, Zhuang, Yuan, primary, Datta, Jyotishka, primary, Dunson, David B., primary, and Davé, Sandeep S., primary

Published
2023
Full Text
View/download PDF

3. Supplementary Tables S1 - S10 from The Genetic Basis of Hepatosplenic T-cell Lymphoma

Author

McKinney, Matthew, primary, Moffitt, Andrea B., primary, Gaulard, Philippe, primary, Travert, Marion, primary, De Leval, Laurence, primary, Nicolae, Alina, primary, Raffeld, Mark, primary, Jaffe, Elaine S., primary, Pittaluga, Stefania, primary, Xi, Liqiang, primary, Heavican, Tayla, primary, Iqbal, Javeed, primary, Belhadj, Karim, primary, Delfau-Larue, Marie Helene, primary, Fataccioli, Virginie, primary, Czader, Magdalena B., primary, Lossos, Izidore S., primary, Chapman-Fredricks, Jennifer R., primary, Richards, Kristy L., primary, Fedoriw, Yuri, primary, Ondrejka, Sarah L., primary, Hsi, Eric D., primary, Low, Lawrence, primary, Weisenburger, Dennis, primary, Chan, Wing C., primary, Mehta-Shah, Neha, primary, Horwitz, Steven, primary, Bernal-Mizrachi, Leon, primary, Flowers, Christopher R., primary, Beaven, Anne W., primary, Parihar, Mayur, primary, Baseggio, Lucile, primary, Parrens, Marie, primary, Moreau, Anne, primary, Sujobert, Pierre, primary, Pilichowska, Monika, primary, Evens, Andrew M., primary, Chadburn, Amy, primary, Au-Yeung, Rex K.H., primary, Srivastava, Gopesh, primary, Choi, William W. L., primary, Goodlad, John R., primary, Aurer, Igor, primary, Basic-Kinda, Sandra, primary, Gascoyne, Randy D., primary, Davis, Nicholas S., primary, Li, Guojie, primary, Zhang, Jenny, primary, Rajagopalan, Deepthi, primary, Reddy, Anupama, primary, Love, Cassandra, primary, Levy, Shawn, primary, Zhuang, Yuan, primary, Datta, Jyotishka, primary, Dunson, David B., primary, and Davé, Sandeep S., primary

Published
2023
Full Text
View/download PDF

4. Supplementary Methods, Figures S1 - S9 from The Genetic Basis of Hepatosplenic T-cell Lymphoma

Author

McKinney, Matthew, primary, Moffitt, Andrea B., primary, Gaulard, Philippe, primary, Travert, Marion, primary, De Leval, Laurence, primary, Nicolae, Alina, primary, Raffeld, Mark, primary, Jaffe, Elaine S., primary, Pittaluga, Stefania, primary, Xi, Liqiang, primary, Heavican, Tayla, primary, Iqbal, Javeed, primary, Belhadj, Karim, primary, Delfau-Larue, Marie Helene, primary, Fataccioli, Virginie, primary, Czader, Magdalena B., primary, Lossos, Izidore S., primary, Chapman-Fredricks, Jennifer R., primary, Richards, Kristy L., primary, Fedoriw, Yuri, primary, Ondrejka, Sarah L., primary, Hsi, Eric D., primary, Low, Lawrence, primary, Weisenburger, Dennis, primary, Chan, Wing C., primary, Mehta-Shah, Neha, primary, Horwitz, Steven, primary, Bernal-Mizrachi, Leon, primary, Flowers, Christopher R., primary, Beaven, Anne W., primary, Parihar, Mayur, primary, Baseggio, Lucile, primary, Parrens, Marie, primary, Moreau, Anne, primary, Sujobert, Pierre, primary, Pilichowska, Monika, primary, Evens, Andrew M., primary, Chadburn, Amy, primary, Au-Yeung, Rex K.H., primary, Srivastava, Gopesh, primary, Choi, William W. L., primary, Goodlad, John R., primary, Aurer, Igor, primary, Basic-Kinda, Sandra, primary, Gascoyne, Randy D., primary, Davis, Nicholas S., primary, Li, Guojie, primary, Zhang, Jenny, primary, Rajagopalan, Deepthi, primary, Reddy, Anupama, primary, Love, Cassandra, primary, Levy, Shawn, primary, Zhuang, Yuan, primary, Datta, Jyotishka, primary, Dunson, David B., primary, and Davé, Sandeep S., primary

Published
2023
Full Text
View/download PDF

5. Synaptic, transcriptional and chromatin genes disrupted in autism

Author

De Rubeis, Silvia, He, Xin, Goldberg, Arthur P., Poultney, Christopher S., Samocha, Kaitlin, Cicek, Ercument A., Kou, Yan, Liu, Li, Fromer, Menachem, Walker, Susan, Singh, Tarjinder, Klei, Lambertus, Kosmicki, Jack, Fu, Shih-Chen, Aleksic, Branko, Biscaldi, Monica, Bolton, Patrick F., Brownfeld, Jessica M., Cai, Jinlu, Campbell, Nicholas G., Carracedo, Angel, Chahrour, Maria H., Chiocchetti, Andreas G., Coon, Hilary, Crawford, Emily L., Crooks, Lucy, Curran, Sarah R., Dawson, Geraldine, Duketis, Eftichia, Fernandez, Bridget A., Gallagher, Louise, Geller, Evan, Guter, Stephen J., Hill, Sean R., Ionita-Laza, Iuliana, Gonzalez, Patricia Jimenez, Kilpinen, Helena, Klauck, Sabine M., Kolevzon, Alexander, Lee, Irene, Lei, Jing, Lehtimäki, Terho, Lin, Chiao-Feng, Maʼayan, Avi, Marshall, Christian R., McInnes, Alison L., Neale, Benjamin, Owen, Michael J., Ozaki, Norio, Parellada, Mara, Parr, Jeremy R., Purcell, Shaun, Puura, Kaija, Rajagopalan, Deepthi, Rehnström, Karola, Reichenberg, Abraham, Sabo, Aniko, Sachse, Michael, Sanders, Stephan J., Schafer, Chad, Schulte-Rüther, Martin, Skuse, David, Stevens, Christine, Szatmari, Peter, Tammimies, Kristiina, Valladares, Otto, Voran, Annette, Wang, Li-San, Weiss, Lauren A., Willsey, Jeremy A., Yu, Timothy W., Yuen, Ryan K. C., Cook, Edwin H., Freitag, Christine M., Gill, Michael, Hultman, Christina M., Lehner, Thomas, Palotie, Aarno, Schellenberg, Gerard D., Sklar, Pamela, State, Matthew W., Sutcliffe, James S., Walsh, Christopher A., Scherer, Stephen W., Zwick, Michael E., Barrett, Jeffrey C., Cutler, David J., Roeder, Kathryn, Devlin, Bernie, Daly, Mark J., and Buxbaum, Joseph D.

Published
2014
Full Text
View/download PDF

7. Genetic and Functional Drivers of Diffuse Large B Cell Lymphoma

Author

Reddy, Anupama, Zhang, Jenny, Davis, Nicholas S, Moffitt, Andrea B, Love, Cassandra L, Waldrop, Alexander, Leppa, Sirpa, Pasanen, Annika, Meriranta, Leo, Karjalainen-Lindsberg, Marja-Liisa, Nørgaard, Peter, Pedersen, Mette, Gang, Anne O, Høgdall, Estrid, Heavican, Tayla B, Lone, Waseem, Iqbal, Javeed, Qin, Qiu, Li, Guojie, Kim, So Young, Healy, Jane, Richards, Kristy L, Fedoriw, Yuri, Bernal-Mizrachi, Leon, Koff, Jean L, Staton, Ashley D, Flowers, Christopher R, Paltiel, Ora, Goldschmidt, Neta, Calaminici, Maria, Clear, Andrew, Gribben, John, Nguyen, Evelyn, Czader, Magdalena B, Ondrejka, Sarah L, Collie, Angela, Hsi, Eric D, Tse, Eric, Au-Yeung, Rex K H, Kwong, Yok-Lam, Srivastava, Gopesh, Choi, William W L, Evens, Andrew M, Pilichowska, Monika, Sengar, Manju, Reddy, Nishitha, Li, Shaoying, Chadburn, Amy, Gordon, Leo I, Jaffe, Elaine S, Levy, Shawn, Rempel, Rachel, Tzeng, Tiffany, Happ, Lanie E., Dave, Tushar, Rajagopalan, Deepthi, Datta, Jyotishka, Dunson, David B., Dave, Sandeep S., Reddy, Anupama, Zhang, Jenny, Davis, Nicholas S, Moffitt, Andrea B, Love, Cassandra L, Waldrop, Alexander, Leppa, Sirpa, Pasanen, Annika, Meriranta, Leo, Karjalainen-Lindsberg, Marja-Liisa, Nørgaard, Peter, Pedersen, Mette, Gang, Anne O, Høgdall, Estrid, Heavican, Tayla B, Lone, Waseem, Iqbal, Javeed, Qin, Qiu, Li, Guojie, Kim, So Young, Healy, Jane, Richards, Kristy L, Fedoriw, Yuri, Bernal-Mizrachi, Leon, Koff, Jean L, Staton, Ashley D, Flowers, Christopher R, Paltiel, Ora, Goldschmidt, Neta, Calaminici, Maria, Clear, Andrew, Gribben, John, Nguyen, Evelyn, Czader, Magdalena B, Ondrejka, Sarah L, Collie, Angela, Hsi, Eric D, Tse, Eric, Au-Yeung, Rex K H, Kwong, Yok-Lam, Srivastava, Gopesh, Choi, William W L, Evens, Andrew M, Pilichowska, Monika, Sengar, Manju, Reddy, Nishitha, Li, Shaoying, Chadburn, Amy, Gordon, Leo I, Jaffe, Elaine S, Levy, Shawn, Rempel, Rachel, Tzeng, Tiffany, Happ, Lanie E., Dave, Tushar, Rajagopalan, Deepthi, Datta, Jyotishka, Dunson, David B., and Dave, Sandeep S.

Abstract

Diffuse large B cell lymphoma (DLBCL) is the most common form of blood cancer and is characterized by a striking degree of genetic and clinical heterogeneity. This heterogeneity poses a major barrier to understanding the genetic basis of the disease and its response to therapy. Here, we performed an integrative analysis of whole-exome sequencing and transcriptome sequencing in a cohort of 1,001 DLBCL patients to comprehensively define the landscape of 150 genetic drivers of the disease. We characterized the functional impact of these genes using an unbiased CRISPR screen of DLBCL cell lines to define oncogenes that promote cell growth. A prognostic model comprising these genetic alterations outperformed current established methods: cell of origin, the International Prognostic Index comprising clinical variables, and dual MYC and BCL2 expression. These results comprehensively define the genetic drivers and their functional roles in DLBCL to identify new therapeutic opportunities in the disease.

Published
2017

9. Genetic and Functional Drivers of Diffuse Large B Cell Lymphoma

Author

Reddy, Anupama, primary, Zhang, Jenny, additional, Davis, Nicholas S., additional, Moffitt, Andrea B., additional, Love, Cassandra L., additional, Waldrop, Alexander, additional, Leppa, Sirpa, additional, Pasanen, Annika, additional, Meriranta, Leo, additional, Karjalainen-Lindsberg, Marja-Liisa, additional, Nørgaard, Peter, additional, Pedersen, Mette, additional, Gang, Anne O., additional, Høgdall, Estrid, additional, Heavican, Tayla B., additional, Lone, Waseem, additional, Iqbal, Javeed, additional, Qin, Qiu, additional, Li, Guojie, additional, Kim, So Young, additional, Healy, Jane, additional, Richards, Kristy L., additional, Fedoriw, Yuri, additional, Bernal-Mizrachi, Leon, additional, Koff, Jean L., additional, Staton, Ashley D., additional, Flowers, Christopher R., additional, Paltiel, Ora, additional, Goldschmidt, Neta, additional, Calaminici, Maria, additional, Clear, Andrew, additional, Gribben, John, additional, Nguyen, Evelyn, additional, Czader, Magdalena B., additional, Ondrejka, Sarah L., additional, Collie, Angela, additional, Hsi, Eric D., additional, Tse, Eric, additional, Au-Yeung, Rex K.H., additional, Kwong, Yok-Lam, additional, Srivastava, Gopesh, additional, Choi, William W.L., additional, Evens, Andrew M., additional, Pilichowska, Monika, additional, Sengar, Manju, additional, Reddy, Nishitha, additional, Li, Shaoying, additional, Chadburn, Amy, additional, Gordon, Leo I., additional, Jaffe, Elaine S., additional, Levy, Shawn, additional, Rempel, Rachel, additional, Tzeng, Tiffany, additional, Happ, Lanie E., additional, Dave, Tushar, additional, Rajagopalan, Deepthi, additional, Datta, Jyotishka, additional, Dunson, David B., additional, and Dave, Sandeep S., additional

Published
2017
Full Text
View/download PDF

11. The Genetic Basis of Hepatosplenic T-cell Lymphoma

Author

McKinney, Matthew, primary, Moffitt, Andrea B., additional, Gaulard, Philippe, additional, Travert, Marion, additional, De Leval, Laurence, additional, Nicolae, Alina, additional, Raffeld, Mark, additional, Jaffe, Elaine S., additional, Pittaluga, Stefania, additional, Xi, Liqiang, additional, Heavican, Tayla, additional, Iqbal, Javeed, additional, Belhadj, Karim, additional, Delfau-Larue, Marie Helene, additional, Fataccioli, Virginie, additional, Czader, Magdalena B., additional, Lossos, Izidore S., additional, Chapman-Fredricks, Jennifer R., additional, Richards, Kristy L., additional, Fedoriw, Yuri, additional, Ondrejka, Sarah L., additional, Hsi, Eric D., additional, Low, Lawrence, additional, Weisenburger, Dennis, additional, Chan, Wing C., additional, Mehta-Shah, Neha, additional, Horwitz, Steven, additional, Bernal-Mizrachi, Leon, additional, Flowers, Christopher R., additional, Beaven, Anne W., additional, Parihar, Mayur, additional, Baseggio, Lucile, additional, Parrens, Marie, additional, Moreau, Anne, additional, Sujobert, Pierre, additional, Pilichowska, Monika, additional, Evens, Andrew M., additional, Chadburn, Amy, additional, Au-Yeung, Rex K.H., additional, Srivastava, Gopesh, additional, Choi, William W. L., additional, Goodlad, John R., additional, Aurer, Igor, additional, Basic-Kinda, Sandra, additional, Gascoyne, Randy D., additional, Davis, Nicholas S., additional, Li, Guojie, additional, Zhang, Jenny, additional, Rajagopalan, Deepthi, additional, Reddy, Anupama, additional, Love, Cassandra, additional, Levy, Shawn, additional, Zhuang, Yuan, additional, Datta, Jyotishka, additional, Dunson, David B., additional, and Davé, Sandeep S., additional

Published
2017
Full Text
View/download PDF

12. SETD2 Functional Loss through Mutation or Genetic Deletion Promotes Expansion of Normal and Malignant γδ T Cells through Loss of Tumor Suppressor Function and Upregulation of Oncogenic Pathways

Author

McKinney, Matthew S., primary, Moffitt, Andrea B., additional, Rempel, Rachel E, additional, Rajagopalan, Deepthi, additional, Healy, Jane, additional, Tzeng, Tiffany, additional, Datta, Jyotishka, additional, Love, Cassandra, additional, Dunson, David, additional, Zhuang, Yuan, additional, and Dave, Sandeep, additional

Published
2016
Full Text
View/download PDF

13. Integrative Genetic and Clinical Analysis through Whole Exome Sequencing in 1001 Diffuse Large B Cell Lymphoma (DLBCL) Patients Reveals Novel Disease Drivers and Risk Groups

Author

Zhang, Jenny, primary, Reddy, Anupama, additional, Love, Cassandra, additional, Moffitt, Andrea B., additional, Rajagopalan, Deepthi, additional, Leppä, Sirpa, additional, Pasanen, Annika, additional, Meriranta, Leo, additional, Karjalainen-Lindsberg, Marja-Liisa, additional, Norgaard, Peter H, additional, Pederson, Mette, additional, Ortved Gang, Anne, additional, Hogdall, Estrid, additional, Richards, Kristy L., additional, Fedoriw, Yuri D., additional, Bernal-Mizrachi, Leon, additional, Koff, Jean L., additional, Staton, Ashley D., additional, Flowers, Christopher, additional, Paltiel-Clarfield, Ora, additional, Goldschmidt, Neta, additional, Calaminici, Maria, additional, Clear, Andrew James, additional, Gribben, John, additional, Nguyen, Evelyn, additional, Czader, Magdalena, additional, Ondrejka, Sarah Lynn, additional, Collie, Angela, additional, Hsi, Eric D, additional, au-Yeung, Rex, additional, Yok-Lam, Kwong, additional, Choi, Wai Lap, additional, Srivastava, Gopesh, additional, Evens, Andrew M, additional, Pilichowska, Monika, additional, Sengar, Manju, additional, Reddy, Nishitha, additional, Li, Shaoying, additional, Jaffe, Elaine S., additional, Tzeng, Tiffany, additional, Datta, Jyotishka, additional, Dunson, David, additional, and Dave, Sandeep, additional

Published
2016
Full Text
View/download PDF

14. Whole Exome Sequencing of Type 1 and Type 2 Enteropathy-Associated T Cell Lymphoma Reveals Genetic Basis of Eatl Oncogenesis

Author

Ondrejka, Sarah Lynn, primary, Moffitt, Andrea B., additional, Tse, Eric, additional, Hsi, Eric D., additional, Goodlad, John R., additional, au-Yeung, Rex, additional, Kwong, Yok-Lam, additional, Srivastava, Gopesh, additional, Gascoyne, Randy D., additional, Rajagopalan, Deepthi, additional, Love, Cassandra, additional, and Dave, Sandeep, additional

Published
2015
Full Text
View/download PDF

16. Integrative Analysis of 1001 Diffuse Large B Cell Lymphoma Identifies Novel Oncogenic Roles for Rhoa

Author

Zhang, Jenny, Reddy, Anupama, Davis, Nicholas, Moffitt, Andrea, Love, Cassandra, Waldrop, Alexander, Leppa, Sirpa, Pasanen, Annika, Meriranta, Leo, Karjalainen-Lindsberg, Marja-Liisa, Norgaard, Peter H., Pedersen, Mette Ø, Gang, Anne Ortved, Hogdall, Estrid, Heavican, Tayla, Lone, Waseem, Iqbal, Javeed, Li, Guojie, Kim, So Young, Healy, Jane, Richards, Kristy L., Fedoriw, Yuri, Bernal-Mizrachi, Leon, Koff, Jean L., Staton, Ashley D., Flowers, Christopher, Paltiel-Clarfield, Ora, Goldschmidt, Neta, Calaminici, Maria, Clear, Andrew James, Gribben, John G., Nguyen, Evelyn, Czader, Magdalena, Ondrejka, Sarah L., Collie, Angela, Hsi, Eric D., Tse, Eric, Au-Yeung, Rex, Kwong, Yok-Lam, Srivastava, Gopesh, Choi, William, Evens, Andrew M, Pilichowska, Monika, Sengar, Manju, Reddy, Nishitha, Li, Shaoying, Chadburn, Amy, Gordon, Leo I., Jaffe, Elaine S., Rempel, Rachel, Tzeng, Tiffany, Dave, Tushar, Happ, Lanie, Rajagopalan, Deepthi, Datta, Jyotishka, Dunson, David, and Dave, Sandeep

Published
2017
Full Text
View/download PDF

17. Enteropathy-associated T cell lymphoma subtypes are characterized by loss of function of SETD2

Author

Zhuang, Yuan, Gascoyne, Randy D., Palus, Brooke C., Dave, Sandeep S., Tzeng, Tiffany J., Yu, Jiayu, Datta, Jyotishka, McKinney, Matthew, Rajagopalan, Deepthi, Smith, Eileen C., Tse, Eric, Iqbal, Javeed, Naresh, Kikkeri, Davis, Nicholas S., Ondrejka, Sarah L., Goodlad, John R., Mannisto, Susanna, Rempel, Rachel E., Kovanen, Panu E., Said, Jonathan, Richards, Kristy L., Chadburn, Amy, Leppa, Sirpa, Srivastava, Gopesh, Villa, Diego, Hsi, Eric D., Teh, Chun Huat, Love, Cassandra, Au-Yeung, Rex K.H., Kwong, Yok-Lam, Moffitt, Andrea B., Healy, Jane A., Levy, Shawn, Dunson, David B., Lugar, Patricia L., and Czader, Magdalena B.

Subjects
3. Good health
Abstract

Enteropathy-associated T cell lymphoma (EATL) is a lethal, and the most common, neoplastic complication of celiac disease. Here, we defined the genetic landscape of EATL through whole-exome sequencing of 69 EATL tumors. SETD2 was the most frequently silenced gene in EATL (32% of cases). The JAK-STAT pathway was the most frequently mutated pathway, with frequent mutations in STAT5B as well as JAK1 , JAK3 , STAT3 , and SOCS1 . We also identified mutations in KRAS , TP53 , and TERT . Type I EATL and type II EATL (monomorphic epitheliotropic intestinal T cell lymphoma) had highly overlapping genetic alterations indicating shared mechanisms underlying their pathogenesis. We modeled the effects of SETD2 loss in vivo by developing a T cell–specific knockout mouse. These mice manifested an expansion of γδ T cells, indicating novel roles for SETD2 in T cell development and lymphomagenesis. Our data render the most comprehensive genetic portrait yet of this uncommon but lethal disease and may inform future classification schemes.

18. Id2 Collaborates with Id3 To Suppress Invariant NKT and Innate-like Tumors.

Author

Jia Li, Roy, Sumedha, Young-Mi Kim, Shibo Li, Baojun Zhang, Love, Cassandra, Reddy, Anupama, Rajagopalan, Deepthi, Dave, Sandeep, Diehl, Anna Mae, and Yuan Zhuang

Subjects
*DNA-binding proteins, *CELL proliferation, *TUMOR suppressor proteins, *BURKITT'S lymphoma, *T cells
Abstract

Inhibitor of DNA binding (Id) proteins, including Id1-4, are transcriptional regulators involved in promoting cell proliferation and survival in various cell types. Although upregulation of Id proteins is associated with a broad spectrum of tumors, recent studies have identified that Id3 plays a tumor-suppressor role in the development of Burkitt's lymphoma in humans and hepatosplenic T cell lymphomas in mice. In this article, we report rapid lymphoma development in Id2/Id3 double-knockout mice that is caused by unchecked expansion of invariant NKT (iNKT) cells or a unique subset of innate-like CDld-independent T cells. These populations began to expand in neonatal mice and, upon malignant transformation, resulted in mortality between 3 and 11 mo of age. The malignant cells also gave rise to lymphomas upon transfer to Rag-deficient and wild-type hosts, reaffirming their inherent tumorigenic potential. Microarray analysis revealed a significantly modified program in these neonatal iNKT cells that ultimately led to their malignant transformation. The lymphoma cells demonstrated chromosome instability along with upregulation of several signaling pathways, including the cytokine-cytokine receptor interaction pathway, which can promote their expansion and migration. Dysregulation of genes with reported driver mutations and the N F - κ B pathway were found to be shared between Id2/Id3 double-knockout lymphomas and human NKT tumors. Our work identifies a distinct premalignant state and multiple tumorigenic pathways caused by loss of function of Id2 and Id3. Thus, conditional deletion of Id2 and Id3 in developing T cells establishes a unique animal model for iNKT and relevant innate-like lymphomas. [ABSTRACT FROM AUTHOR]

Published
2017
Full Text
View/download PDF

19. Genetic and Functional Drivers of Diffuse Large B Cell Lymphoma.

Author

Davis, Nicholas S., Moffitt, Andrea B., Love, Cassandra L., Waldrop, Alexander, Qin, Qiu, Li, Guojie, Kim, So Young, Healy, Jane, Rempel, Rachel, Tzeng, Tiffany, Happ, Lanie E., Dave, Tushar, Rajagopalan, Deepthi, Datta, Jyotishka, Reddy, Anupama, Zhang, Jenny, Dave, Sandeep S., Nguyen, Evelyn, Czader, Magdalena B., and Ondrejka, Sarah L.

Subjects
*HEMATOLOGIC malignancies, *CRISPRS, *HETEROGENEITY, *EXOMES, *ONCOGENES
Abstract

Summary Diffuse large B cell lymphoma (DLBCL) is the most common form of blood cancer and is characterized by a striking degree of genetic and clinical heterogeneity. This heterogeneity poses a major barrier to understanding the genetic basis of the disease and its response to therapy. Here, we performed an integrative analysis of whole-exome sequencing and transcriptome sequencing in a cohort of 1,001 DLBCL patients to comprehensively define the landscape of 150 genetic drivers of the disease. We characterized the functional impact of these genes using an unbiased CRISPR screen of DLBCL cell lines to define oncogenes that promote cell growth. A prognostic model comprising these genetic alterations outperformed current established methods: cell of origin, the International Prognostic Index comprising clinical variables, and dual MYC and BCL2 expression. These results comprehensively define the genetic drivers and their functional roles in DLBCL to identify new therapeutic opportunities in the disease. [ABSTRACT FROM AUTHOR]

Published
2017
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results