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2. Impact of rabbit anti-thymocyte globulin (ATG) exposure on outcomes after ex vivo T-cell–depleted hematopoietic cell transplantation in pediatric and young adult patients

Author

Lakkaraja, Madhavi, Mauguen, Audrey, Boulad, Farid, Cancio, Maria I., Curran, Kevin J., Harris, Andrew C., Kernan, Nancy A., Klein, Elizabeth, Kung, Andrew L., Oved, Joseph, Prockop, Susan, Scaradavou, Andromachi, Spitzer, Barbara, O'Reilly, Richard J., and Boelens, Jaap Jan

Published
2024
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3. Successful treatment and integrated genomic analysis of an infant with FIP1L1-RARA fusion-associated myeloid neoplasm

Author

Miltiadous, Oriana, Petrova-Drus, Kseniya, Kaicker, Shipra, Mathew, Susan, Kluk, Michael, Geyer, Julia Turbiner, Rodriguez-Sanchez, M Irene, Bouvier, Nancy, Inghirami, Giorgio GA, Stieglitz, Elliot, Nafa, Khedoudja, Benayed, Ryma, Richardson, Michelle, Anderson, Wade, Benhamida, Jamal, You, Daoqi, Londono, Dory, Kung, Andrew L, Prockop, Susan, Roshal, Mikhail, Zhang, Yanming, and Shukla, Neerav Narendra

Subjects
Childhood Leukemia, Cancer, Hematology, Stem Cell Research, Transplantation, Pediatric, Pediatric Cancer, Pediatric Research Initiative, Rare Diseases, Child, Hematopoietic Stem Cell Transplantation, Humans, Infant, Leukemia, Promyelocytic, Acute, Male, Myeloproliferative Disorders
Abstract

FIP1L1-RARA-a ssociated neoplasm is a very rare and aggressive disease, with only 3 previously reported cases in the literature. Here, we describe a 9-month-old boy who presented with a FIP1L1-RARA fusion-associated myelodysplastic/myeloproliferative neoplasm-like overlap syndrome, with similarities and distinct features to both acute promyelocytic leukemia and juvenile myelomonocytic leukemia. Using a combined approach of chemotherapy, differentiating agents, and allogeneic hematopoietic stem cell transplant (allo-HCT), this patient remains in remission 20 months after allo-HCT. To our knowledge, this is only the second published pediatric case involving this condition and the only case with a favorable long-term outcome. Given the aggressive disease described in the previously published case report, as well as the successful treatment course described, the combinatorial use of chemotherapy, differentiation therapy, and allo-HCT for treatment of FIP1L1-RARA fusion-associated myeloid neoplasms should be considered.

Published
2022

5. Prospective pan-cancer germline testing using MSK-IMPACT informs clinical translation in 751 patients with pediatric solid tumors

Author

Fiala, Elise M, Jayakumaran, Gowtham, Mauguen, Audrey, Kennedy, Jennifer A, Bouvier, Nancy, Kemel, Yelena, Fleischut, Megan Harlan, Maio, Anna, Salo-Mullen, Erin E, Sheehan, Margaret, Arnold, Angela G, Latham, Alicia, Carlo, Maria I, Cadoo, Karen, Murkherjee, Semanti, Slotkin, Emily K, Trippett, Tanya, Glade Bender, Julia, Meyers, Paul A, Wexler, Leonard, Dela Cruz, Filemon S, Cheung, Nai-Kong, Basu, Ellen, Kentsis, Alex, Ortiz, Michael, Francis, Jasmine H, Dunkel, Ira J, Khakoo, Yasmin, Gilheeney, Stephen, Farouk Sait, Sameer, Forlenza, Christopher J, Sulis, Maria, Karajannis, Matthias, Modak, Shakeel, Gerstle, Justin T, Heaton, Todd E, Roberts, Stephen, Yang, Ciyu, Jairam, Sowmya, Vijai, Joseph, Topka, Sabine, Friedman, Danielle N, Stadler, Zsofia K, Robson, Mark, Berger, Michael F, Schultz, Nikolaus, Ladanyi, Marc, O’Reilly, Richard J, Abramson, David H, Ceyhan-Birsoy, Ozge, Zhang, Liying, Mandelker, Diana, Shukla, Neerav N, Kung, Andrew L, Offit, Kenneth, Zehir, Ahmet, and Walsh, Michael F

Subjects
Rare Diseases, Genetic Testing, Genetics, Pediatric, Human Genome, Clinical Research, Pediatric Cancer, Cancer, Aetiology, 2.1 Biological and endogenous factors, Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, Good Health and Well Being, Child, Genetic Predisposition to Disease, Germ Cells, Germ-Line Mutation, Humans, Neoplasms, Prospective Studies
Abstract

The spectrum of germline predisposition in pediatric cancer continues to be realized. Here we report 751 solid tumor patients who underwent prospective matched tumor-normal DNA sequencing and downstream clinical use (clinicaltrials.gov NCT01775072). Germline pathogenic and likely pathogenic (P/LP) variants were reported. One or more P/LP variants were found in 18% (138/751) of individuals when including variants in low, moderate, and high penetrance dominant or recessive genes, or 13% (99/751) in moderate and high penetrance dominant genes. 34% of high or moderate penetrance variants were unexpected based on the patient's diagnosis and previous history. 76% of patients with positive results completed a clinical genetics visit, and 21% had at least one relative undergo cascade testing as a result of this testing. Clinical actionability additionally included screening, risk reduction in relatives, reproductive use, and use of targeted therapies. Germline testing should be considered for all children with cancer.

Published
2021

6. Association between busulfan exposure and survival in patients undergoing a CD34+ selected stem cell transplantation

Author

Tamari, Roni, Scordo, Michael, Kunvarjee, Binni M., Proli, Anthony, Lin, Andrew, Flynn, Jessica, Cho, Christina, Devlin, Sean, Klein, Elizabeth, Boulad, Farid, Cancio, Maria I., Curran, Kevin J., Jakubowski, Ann A., Kernan, Nancy A., Kung, Andrew L., O’Reilly, Richard J., Papadopoulos, Esperanza B., Prockop, Susan, Scaradavou, Andromachi, Shaffer, Brian C., Shah, Gunjan, Spitzer, Barbara, Gyurkocza, Boglarka, Giralt, Sergio A., Perales, Miguel-Angel, and Boelens, Jaap Jan

Published
2023
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7. Validation of a non-oncogene encoded vulnerability to exportin 1 inhibition in pediatric renal tumors

Author

Coutinho, Diego F., Mundi, Prabhjot S., Marks, Lianna J., Burke, Chelsey, Ortiz, Michael V., Diolaiti, Daniel, Bird, Lauren, Vallance, Kelly L., Ibáñez, Glorymar, You, Daoqi, Long, Matthew, Rosales, Nestor, Grunn, Adina, Ndengu, Andoyo, Siddiquee, Armaan, Gaviria, Ervin S., Rainey, Allison R., Fazlollahi, Ladan, Hosoi, Hajime, Califano, Andrea, Kung, Andrew L., and Dela Cruz, Filemon S.

Published
2022
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8. Therapeutic targeting of ATR in alveolar rhabdomyosarcoma

Author

Dorado García, Heathcliff, Pusch, Fabian, Bei, Yi, von Stebut, Jennifer, Ibáñez, Glorymar, Guillan, Kristina, Imami, Koshi, Gürgen, Dennis, Rolff, Jana, Helmsauer, Konstantin, Meyer-Liesener, Stephanie, Timme, Natalie, Bardinet, Victor, Chamorro González, Rocío, MacArthur, Ian C., Chen, Celine Y., Schulz, Joachim, Wengner, Antje M., Furth, Christian, Lala, Birgit, Eggert, Angelika, Seifert, Georg, Hundsoerfer, Patrick, Kirchner, Marieluise, Mertins, Philipp, Selbach, Matthias, Lissat, Andrej, Dubois, Frank, Horst, David, Schulte, Johannes H., Spuler, Simone, You, Daoqi, Dela Cruz, Filemon, Kung, Andrew L., Haase, Kerstin, DiVirgilio, Michela, Scheer, Monika, Ortiz, Michael V., and Henssen, Anton G.

Published
2022
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9. Antithymocyte globulin exposure in CD34+ T-cell–depleted allogeneic hematopoietic cell transplantation

Author

Lakkaraja, Madhavi, Scordo, Michael, Mauguen, Audrey, Cho, Christina, Devlin, Sean, Ruiz, Josel D., Klein, Elizabeth, Avecilla, Scott T., Boulad, Farid, Cancio, Maria I., Curran, Kevin J., Jakubowski, Ann A., Kernan, Nancy A., Kung, Andrew L., O'Reilly, Richard J., Papadopoulos, Esperanza B., Prockop, Susan, van Roessel, Ichelle, Scaradavou, Andromachi, Shaffer, Brian C., Shah, Gunjan, Spitzer, Barbara, Tamari, Roni, Giralt, Sergio A., Perales, Miguel-Angel, and Boelens, Jaap Jan

Published
2022
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10. Two novel assays demonstrate persistent daratumumab exposure in a pediatric patient with delayed engraftment following allogeneic hematopoietic stem cell transplantation

Author

Major-Monfried, Hannah, primary, Hosszu, Kinga, additional, McAvoy, Devin P., additional, Vallone, Alexander, additional, Shukla, Neerav, additional, Gillio, Alfred, additional, Spitzer, Barbara, additional, Kung, Andrew L., additional, Cancio, Maria, additional, Curran, Kevin, additional, Scaradavou, Andromachi, additional, Oved, Joseph H., additional, O'Reilly, Richard J., additional, Boelens, Jaap Jan, additional, and Harris, Andrew C., additional

Published
2024
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11. Regulatory T Cell Reconstitution Is Associated with Acute Graft-Versus-Host Disease in Pediatric and Young Adult Hematopoietic Cell Transplant Recipients

Author

Hosszu, Kinga, primary, McAvoy, Devin, additional, Garcia-Rosa, Moises, additional, White, Charlie, additional, Thomsen, Matthew, additional, Ntrivalas, Evangelos, additional, Klein, Elizabeth, additional, Mauguen, Audrey, additional, Curran, Kevin J., additional, Cancio, Maria I., additional, Scaradavou, Andromachi, additional, Kung, Andrew L., additional, Oved, Joseph H., additional, Perales, Miguel-Angel, additional, Harris, Andrew C., additional, and Boelens, Jaap Jan, additional

Published
2024
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12. Predictors for Recent Thymic Emigrant T Cell Reconstitution after Hematopoietic Cell Transplantation

Author

McAvoy, Devin, primary, Hosszu, Kinga, additional, Vidal, Esther Hadassa, additional, Singh, Katina H, additional, Thomsen, Matthew, additional, Ntrivalas, Evangelos, additional, Klein, Elizabeth, additional, Harris, Andrew C., additional, Curran, Kevin J., additional, Cancio, Maria I., additional, Scaradavou, Andromachi, additional, Oved, Joseph H., additional, Kung, Andrew L., additional, and Boelens, Jaap Jan, additional

Published
2024
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13. Abstract PR01: Identification and pharmacological targeting of treatment-resistant, stem-like breast cancer cells for combination therapy

Author

Worley, Jeremy, primary, Noh, Heeju, additional, You, Daoqi, additional, Turunen, Mikko M, additional, Ding, Hongxu, additional, Paull, Evan, additional, Griffin, Aaron T, additional, Grunn, Adina, additional, Guillan, Kristina, additional, Bush, Erin C, additional, Brosius, Samantha J, additional, Mundi, Prabhjot S, additional, Sims, Peter, additional, Dalerba, Piero, additional, Dela Cruz, Filemon S, additional, Kung, Andrew L, additional, and Califano, Andrea, additional

Published
2024
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15. High-throughput identification of genotype-specific cancer vulnerabilities in mixtures of barcoded tumor cell lines

Author

Yu, Channing, Mannan, Aristotle M, Yvone, Griselda Metta, Ross, Kenneth N, Zhang, Yan-Ling, Marton, Melissa A, Taylor, Bradley R, Crenshaw, Andrew, Gould, Joshua Z, Tamayo, Pablo, Weir, Barbara A, Tsherniak, Aviad, Wong, Bang, Garraway, Levi A, Shamji, Alykhan F, Palmer, Michelle A, Foley, Michael A, Winckler, Wendy, Schreiber, Stuart L, Kung, Andrew L, and Golub, Todd R

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Animals, Cell Line, Tumor, DNA Barcoding, Taxonomic, Drug Resistance, Neoplasm, Genotyping Techniques, High-Throughput Nucleotide Sequencing, Humans, Mice, Neoplasms
Abstract

Hundreds of genetically characterized cell lines are available for the discovery of genotype-specific cancer vulnerabilities. However, screening large numbers of compounds against large numbers of cell lines is currently impractical, and such experiments are often difficult to control. Here we report a method called PRISM that allows pooled screening of mixtures of cancer cell lines by labeling each cell line with 24-nucleotide barcodes. PRISM revealed the expected patterns of cell killing seen in conventional (unpooled) assays. In a screen of 102 cell lines across 8,400 compounds, PRISM led to the identification of BRD-7880 as a potent and highly specific inhibitor of aurora kinases B and C. Cell line pools also efficiently formed tumors as xenografts, and PRISM recapitulated the expected pattern of erlotinib sensitivity in vivo.

Published
2016

16. The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice

Author

Townsend, Elizabeth C, Murakami, Mark A, Christodoulou, Alexandra, Christie, Amanda L, Köster, Johannes, DeSouza, Tiffany A, Morgan, Elizabeth A, Kallgren, Scott P, Liu, Huiyun, Wu, Shuo-Chieh, Plana, Olivia, Montero, Joan, Stevenson, Kristen E, Rao, Prakash, Vadhi, Raga, Andreeff, Michael, Armand, Philippe, Ballen, Karen K, Barzaghi-Rinaudo, Patrizia, Cahill, Sarah, Clark, Rachael A, Cooke, Vesselina G, Davids, Matthew S, DeAngelo, Daniel J, Dorfman, David M, Eaton, Hilary, Ebert, Benjamin L, Etchin, Julia, Firestone, Brant, Fisher, David C, Freedman, Arnold S, Galinsky, Ilene A, Gao, Hui, Garcia, Jacqueline S, Garnache-Ottou, Francine, Graubert, Timothy A, Gutierrez, Alejandro, Halilovic, Ensar, Harris, Marian H, Herbert, Zachary T, Horwitz, Steven M, Inghirami, Giorgio, Intlekofer, Andrew M, Ito, Moriko, Izraeli, Shai, Jacobsen, Eric D, Jacobson, Caron A, Jeay, Sébastien, Jeremias, Irmela, Kelliher, Michelle A, Koch, Raphael, Konopleva, Marina, Kopp, Nadja, Kornblau, Steven M, Kung, Andrew L, Kupper, Thomas S, LeBoeuf, Nicole R, LaCasce, Ann S, Lees, Emma, Li, Loretta S, Look, A Thomas, Murakami, Masato, Muschen, Markus, Neuberg, Donna, Ng, Samuel Y, Odejide, Oreofe O, Orkin, Stuart H, Paquette, Rachel R, Place, Andrew E, Roderick, Justine E, Ryan, Jeremy A, Sallan, Stephen E, Shoji, Brent, Silverman, Lewis B, Soiffer, Robert J, Steensma, David P, Stegmaier, Kimberly, Stone, Richard M, Tamburini, Jerome, Thorner, Aaron R, van Hummelen, Paul, Wadleigh, Martha, Wiesmann, Marion, Weng, Andrew P, Wuerthner, Jens U, Williams, David A, Wollison, Bruce M, Lane, Andrew A, Letai, Anthony, Bertagnolli, Monica M, Ritz, Jerome, Brown, Myles, Long, Henry, Aster, Jon C, Shipp, Margaret A, Griffin, James D, and Weinstock, David M

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Biotechnology, Clinical Trials and Supportive Activities, Orphan Drug, Clinical Research, Hematology, Cancer, Rare Diseases, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Good Health and Well Being, Animals, Antineoplastic Agents, Biomarkers, Tumor, Cell Lineage, Female, Gene Expression Profiling, Genes, p53, Heterografts, Humans, Internet, Isoquinolines, Leukemia, Leukemia, Experimental, Lymphoma, Male, Mice, Mice, Inbred NOD, Molecular Targeted Therapy, Neoplasm Proteins, Neoplasm Transplantation, Phenotype, Piperazines, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, Proteome, Proto-Oncogene Proteins c-mdm2, Random Allocation, Randomized Controlled Trials as Topic, Research Design, Tissue Banks, Transcriptome, Xenograft Model Antitumor Assays, Neurosciences, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

More than 90% of drugs with preclinical activity fail in human trials, largely due to insufficient efficacy. We hypothesized that adequately powered trials of patient-derived xenografts (PDX) in mice could efficiently define therapeutic activity across heterogeneous tumors. To address this hypothesis, we established a large, publicly available repository of well-characterized leukemia and lymphoma PDXs that undergo orthotopic engraftment, called the Public Repository of Xenografts (PRoXe). PRoXe includes all de-identified information relevant to the primary specimens and the PDXs derived from them. Using this repository, we demonstrate that large studies of acute leukemia PDXs that mimic human randomized clinical trials can characterize drug efficacy and generate transcriptional, functional, and proteomic biomarkers in both treatment-naive and relapsed/refractory disease.

Published
2016

17. Toxicity and response after CD19-specific CAR T-cell therapy in pediatric/young adult relapsed/refractory B-ALL

Author

Curran, Kevin J., Margossian, Steven P., Kernan, Nancy A., Silverman, Lewis B., Williams, David A., Shukla, Neerav, Kobos, Rachel, Forlenza, Christopher J., Steinherz, Peter, Prockop, Susan, Boulad, Farid, Spitzer, Barbara, Cancio, Maria I., Boelens, Jaap Jan, Kung, Andrew L., Khakoo, Yasmin, Szenes, Victoria, Park, Jae H., Sauter, Craig S., Heller, Glenn, Wang, Xiuyan, Senechal, Brigitte, O'Reilly, Richard J., Riviere, Isabelle, Sadelain, Michel, and Brentjens, Renier J.

Published
2019
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18. Subclonal Somatic Copy-Number Alterations Emerge and Dominate in Recurrent Osteosarcoma

Author

Kinnaman, Michael D., primary, Zaccaria, Simone, additional, Makohon-Moore, Alvin, additional, Arnold, Brian, additional, Levine, Max F., additional, Gundem, Gunes, additional, Arango Ossa, Juan E., additional, Glodzik, Dominik, additional, Rodríguez-Sánchez, M. Irene, additional, Bouvier, Nancy, additional, Li, Shanita, additional, Stockfisch, Emily, additional, Dunigan, Marisa, additional, Cobbs, Cassidy, additional, Bhanot, Umesh K., additional, You, Daoqi, additional, Mullen, Katelyn, additional, Melchor, Jerry P., additional, Ortiz, Michael V., additional, O'Donohue, Tara J., additional, Slotkin, Emily K., additional, Wexler, Leonard H., additional, Dela Cruz, Filemon S., additional, Hameed, Meera R., additional, Glade Bender, Julia L., additional, Tap, William D., additional, Meyers, Paul A., additional, Papaemmanuil, Elli, additional, Kung, Andrew L., additional, and Iacobuzio-Donahue, Christine A., additional

Published
2023
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20. BET bromodomain proteins regulate enhancer function during adipogenesis

Author

Brown, Jonathan D., Feldman, Zachary B., Doherty, Sean P., Reyes, Jaime M., Rahl, Peter B., Lin, Charles Y., Sheng, Quanhu, Duan, Qiong, Federation, Alexander J., Kung, Andrew L., Haldar, Saptarsi M., Young, Richard A., Plutzky, Jorge, and Bradner, James E.

Published
2018

22. Recurrent EML4–NTRK3 fusions in infantile fibrosarcoma and congenital mesoblastic nephroma suggest a revised testing strategy

Author

Church, Alanna J, Calicchio, Monica L, Nardi, Valentina, Skalova, Alena, Pinto, Andre, Dillon, Deborah A, Gomez-Fernandez, Carmen R, Manoj, Namitha, Haimes, Josh D, Stahl, Joshua A, Dela Cruz, Filemon S, Tannenbaum-Dvir, Sarah, Glade-Bender, Julia L, Kung, Andrew L, DuBois, Steven G, Kozakewich, Harry P, Janeway, Katherine A, Perez-Atayde, Antonio R, and Harris, Marian H

Published
2018
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23. Targeting MYCN in Neuroblastoma by BET Bromodomain Inhibition

Author

Puissant, Alexandre, Frumm, Stacey M, Alexe, Gabriela, Bassil, Christopher F, Qi, Jun, Chanthery, Yvan H, Nekritz, Erin A, Zeid, Rhamy, Gustafson, William Clay, Greninger, Patricia, Garnett, Matthew J, McDermott, Ultan, Benes, Cyril H, Kung, Andrew L, Weiss, William A, Bradner, James E, and Stegmaier, Kimberly

Subjects
Human Genome, Pediatric Research Initiative, Genetics, Pediatric Cancer, Clinical Research, Pediatric, Neuroblastoma, Neurosciences, Rare Diseases, Cancer, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Animals, Apoptosis, Azepines, Cell Cycle Checkpoints, Cell Cycle Proteins, Cell Growth Processes, Cell Line, Tumor, Child, Down-Regulation, Female, Gene Amplification, Humans, Mice, Molecular Targeted Therapy, N-Myc Proto-Oncogene Protein, Nuclear Proteins, Oncogene Proteins, Promoter Regions, Genetic, Protein Structure, Tertiary, Proto-Oncogene Proteins c-myc, RNA, Small Interfering, Transcription Factors, Transfection, Triazoles, Xenograft Model Antitumor Assays, Oncology and Carcinogenesis
Abstract

Bromodomain inhibition comprises a promising therapeutic strategy in cancer, particularly for hematologic malignancies. To date, however, genomic biomarkers to direct clinical translation have been lacking. We conducted a cell-based screen of genetically defined cancer cell lines using a prototypical inhibitor of BET bromodomains. Integration of genetic features with chemosensitivity data revealed a robust correlation between MYCN amplification and sensitivity to bromodomain inhibition. We characterized the mechanistic and translational significance of this finding in neuroblastoma, a childhood cancer with frequent amplification of MYCN. Genome-wide expression analysis showed downregulation of the MYCN transcriptional program accompanied by suppression of MYCN transcription. Functionally, bromodomain-mediated inhibition of MYCN impaired growth and induced apoptosis in neuroblastoma. BRD4 knockdown phenocopied these effects, establishing BET bromodomains as transcriptional regulators of MYCN. BET inhibition conferred a significant survival advantage in 3 in vivo neuroblastoma models, providing a compelling rationale for developing BET bromodomain inhibitors in patients with neuroblastoma.

Published
2013

26. Clonal hematopoiesis in survivors of childhood cancer

Author

Novetsky Friedman, Danielle, primary, Chan, Irenaeus C. C., additional, Moskowitz, Chaya S., additional, Li, Shanita, additional, Turner, Kimberly, additional, Liu, Jie, additional, Bouvier, Nancy, additional, Walsh, Michael F., additional, Spitzer, Barbara, additional, Kung, Andrew L., additional, Berger, Michael, additional, Cooper, Megan A., additional, Pusic, Iskra, additional, Uy, Geoffrey, additional, Link, Daniel, additional, Druley, Todd E., additional, Diaz, Luis A., additional, Levine, Ross L., additional, Shukla, Neerav, additional, and Bolton, Kelly L., additional

Published
2023
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32. A HIF1alpha regulatory loop links hypoxia and mitochondrial signals in pheochromocytomas.

Author

Dahia, Patricia LM, Ross, Ken N, Wright, Matthew E, Hayashida, César Y, Santagata, Sandro, Barontini, Marta, Kung, Andrew L, Sanso, Gabriela, Powers, James F, Tischler, Arthur S, Hodin, Richard, Heitritter, Shannon, Moore, Francis, Dluhy, Robert, Sosa, Julie Ann, Ocal, I Tolgay, Benn, Diana E, Marsh, Deborah J, Robinson, Bruce G, Schneider, Katherine, Garber, Judy, Arum, Seth M, Korbonits, Márta, Grossman, Ashley, Pigny, Pascal, Toledo, Sérgio PA, Nosé, Vania, Li, Cheng, and Stiles, Charles D

Subjects
Genetics, Developmental Biology
Abstract

Pheochromocytomas are neural crest-derived tumors that arise from inherited or sporadic mutations in at least six independent genes. The proteins encoded by these multiple genes regulate distinct functions. We show here a functional link between tumors with VHL mutations and those with disruption of the genes encoding for succinate dehydrogenase (SDH) subunits B (SDHB) and D (SDHD). A transcription profile of reduced oxidoreductase is detected in all three of these tumor types, together with an angiogenesis/hypoxia profile typical of VHL dysfunction. The oxidoreductase defect, not previously detected in VHL-null tumors, is explained by suppression of the SDHB protein, a component of mitochondrial complex II. The decrease in SDHB is also noted in tumors with SDHD mutations. Gain-of-function and loss-of-function analyses show that the link between hypoxia signals (via VHL) and mitochondrial signals (via SDH) is mediated by HIF1alpha. These findings explain the shared features of pheochromocytomas with VHL and SDH mutations and suggest an additional mechanism for increased HIF1alpha activity in tumors.

Published
2005

35. Abstract 2149: A whole genome sequencing classifier of homologous recombination deficiency

Author

Hadi, Kevin, primary, Gundem, Gunes, additional, Levine, Max F., additional, Deshpande, Aditya, additional, Patel, Minal, additional, Skzrypczak, Stan, additional, Assaad, Majd Al, additional, Mosquera, Juan Miguel, additional, Elemento, Olivier, additional, Kung, Andrew L., additional, Medina-Martínez, Juan S., additional, and Papaemmanuil, Elli, additional

Published
2023
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36. Abstract 3142: Enabling whole genome sequencing analysis from FFPE specimens in clinical oncology

Author

Domenico, Dylan, primary, Gundem, Gunes, additional, Levine, Max F., additional, Arango-Ossa, Juanes E., additional, Robbe, Pauline, additional, Asimomitis, Georgios, additional, Cobbs, Cassidy, additional, Stockfisch, Emily, additional, Senz, Janine, additional, Cochrane, Dawn, additional, Mohibullah, Neeman, additional, Shukla, Neerav, additional, Shah, Sohrab P., additional, McPherson, Andrew, additional, Schuh, Anna, additional, Kung, Andrew L., additional, and Papaemmanuil, Elli, additional

Published
2023
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37. Overcoming Barriers to Tumor Genomic Profiling through Direct-to-Patient Outreach

Author

Doe-Tetteh, Seyram A., primary, Camp, Sabrina Y., additional, Reales, Dalicia, additional, Crowdis, Jett, additional, Noronha, Anne Marie, additional, Wolff, Bernadette, additional, Alano, Tina, additional, Galle, Jesse, additional, Selcuklu, S. Duygu, additional, Viale, Agnes, additional, Socci, Nicholas D., additional, Liu, Ying L., additional, Tew, William P., additional, Aghajanian, Carol, additional, Ladanyi, Marc, additional, He, Meng Xiao, additional, AlDubayan, Saud H., additional, Mazor, Roei David, additional, Shpilberg, Ofer, additional, Hershkovitz-Rokah, Oshrat, additional, Riancho, Jose A., additional, Hernandez, Jose L., additional, Gonzalez-Vela, M. Carmen, additional, Buthorn, Justin J., additional, Wilson, Manda, additional, Webber, Amy E., additional, Yabe, Mariko, additional, Petrova-Drus, Kseniya, additional, Rosenblum, Marc, additional, Durham, Benjamin H., additional, Abdel-Wahab, Omar, additional, Berger, Michael F., additional, Donoghue, Mark T.A., additional, Kung, Andrew L., additional, Glade Bender, Julia, additional, Shukla, Neerav N., additional, Funt, Samuel A., additional, Dogan, Ahmet, additional, Soslow, Robert A., additional, Al-Ahmadie, Hikmat, additional, Feldman, Darren R., additional, Van Allen, Eliezer M., additional, Diamond, Eli L., additional, and Solit, David B., additional

Published
2023
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40. Impact of Rabbit Anti-Thymocyte Globulin (rATG) Exposure in Ex Vivo T-Cell Depleted Hematopoietic Cell Transplantation in Children and Young Adults

Author

Lakkaraja, Madhavi, primary, Mauguen, Audrey, additional, Boulad, Farid, additional, Cancio, Maria I., additional, Curran, Kevin J., additional, Harris, Andrew C., additional, Kernan, Nancy A., additional, Klein, Elizabeth, additional, Kung, Andrew L., additional, Oved, Joseph H., additional, Prockop, Susan E., additional, Scaradavou, Andromachi, additional, Spitzer, Barbara, additional, O’Reilly, Richard J., additional, and Boelens, Jaap-Jan, additional

Published
2023
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41. Clinical Outcomes and Salvage Therapies of Pediatric Patients with Progressive B-ALL Following CD19 Chimeric Antigen Receptor (CAR) T Cell Therapy

Author

Bidgoli, Alan, primary, Yametti, Gloria Contreras, additional, Shahid, Sanam, additional, Harris, Andrew C., additional, Cancio, Maria I., additional, Spitzer, Barbara, additional, Oved, Joseph H., additional, O’Reilly, Richard J., additional, Mauguen, Audrey, additional, Scaradavou, Andromachi, additional, Kung, Andrew L., additional, Boelens, Jaap-Jan, additional, and Curran, Kevin J., additional

Published
2023
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47. Effects of LSD1 Inhibition with Img-7289 on the Leukemia Initiating Cell Population with Induction of Differentiation and Cell Death in Pediatric Relapsed/Refractory AML

Author

Rosenzweig, Jaclyn, primary, Ferreira Coutinho, Diego, additional, Long, Matthew, additional, Souto, Katie, additional, Ibanez Sanchez, Glorymar, additional, Fishkin, Raina, additional, Guillan, Kristina, additional, Siddiquee, Armaan, additional, Calder, Paul, additional, You, Daoqi, additional, Kung, Andrew L., additional, and Dela Cruz, Filemon, additional

Published
2022
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48. Unmatched Whole-Genome Sequencing As a Clinical Tool for Hematological Neoplasms with Significant Utility in Cases with Tumor-in-Normal Contamination

Author

Gutiérrez-Abril, Jesús, primary, Leongamornlert, Daniel, additional, Shukla, Neerav N, additional, Sulis, Maria Luisa, additional, Zhou, Yangyu, additional, Levine, Max F., additional, Barretta, Emilio, additional, Lee, SooWah, additional, Arango-Ossa, Juan E., additional, Gundem, Gunes, additional, Medina-Martínez, Juan S., additional, Patel Wrench, Bela, additional, Moorman, Anthony V., additional, Fielding, Adele K., additional, Kung, Andrew L., additional, and Papaemmanuil, Elli, additional

Published
2022
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50. Abstract 3165: Elucidation and pharmacological targeting of master regulator proteins representing mechanistic determinants of breast cancer stem-like tumor initiating cell state

Author

Worley, Jeremy, primary, Ding, Hongxu, additional, Noh, Heeju, additional, Paull, Evan, additional, Griffin, Aaron T., additional, Grunn, Adina, additional, You, Daoqi, additional, Guillan, Kristina, additional, Bush, Erin, additional, Dalerba, Piero, additional, Sims, Peter, additional, Dela Cruz, Filemon S., additional, Kung, Andrew L., additional, and Califano, Andrea, additional

Published
2022
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