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1,803 results on '"Vega, Francisco"'

1. MSH6-proficient crypt foci in MSH6 constitutional mismatch repair deficiency: reversion of a frameshifted coding microsatellite to its wild-type sequence

Author

Shia, Jinru, Sanchez-Vega, Francisco, Cho, Stanley, Chen, Jie-Fu, Chen, Chin-Tung, Bhanot, Umesh, Urganci, Nil, Firat, Canan, Ntiamoah, Peter, Isidro, Raymond A., Srivastava, Amitabh, Weiser, Martin R., Mandelker, Diana, Vakiani, Efsevia, Boland, C. Richard, Garcia-Aguilar, Julio, and Stadler, Zsofia K.

Published
2024
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5. Increased expression of CD70 in relapsed acute myeloid leukemia after hypomethylating agents

Author

Marques-Piubelli, Mario L., Kumar, Bijender, Basar, Rafet, Panowski, Siler, Srinivasan, Surabhi, Norwood, Kevin, Prashad, Sacha, Szenes, Victoria, Balakumaran, Arun, Arandhya, Akanksha, Lu, Wei, Khan, Khaja, Duenas, Daniela, McAllen, Salome, Gomez, Javier A, Burks, Jared K., Acharyal, Sunil, Borthakur, Gautam, Wang, Wei-Lien, Wang, Wei, Wang, Sa, Solis, Luisa M., Marin, David, Rezvani, Katayoun, Daher, May, and Vega, Francisco

Published
2024
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6. The SWI/SNF chromatin remodeling subunit DPF2 facilitates NRF2-dependent anti-inflammatory and anti-oxidant gene expression

Author

Mas, Gloria, Man, Na, Nakata, Yuichiro, Martinez-Caja, Concepcion, Karl, Daniel L, Beckedorff, Felipe, Tamiro, Francesco, Chen, Chuan, Duffort, Stephanie, Itonaga, Hidehiro, Mookhtiar, Adnan K, Kunkalla, Kranthi, Valencia, Alfredo M, Collings, Clayton K, Kadoch, Cigall, Vega, Francisco, Kogan, Scott C, Morey, Lluis, Bilbao, Daniel, and Nimer, Stephen D

Subjects
Hematology, Genetics, Cancer, Biotechnology, Regenerative Medicine, Stem Cell Research, Stem Cell Research - Nonembryonic - Non-Human, Vaccine Related, Aetiology, Underpinning research, 1.1 Normal biological development and functioning, 2.1 Biological and endogenous factors, Inflammatory and immune system, Mice, Animals, Chromatin, Antioxidants, NF-E2-Related Factor 2, Neoplasms, Chromatin Assembly and Disassembly, Inflammation, Gene Expression, DNA-Binding Proteins, Transcription Factors, Epigenetics, Hematopoietic stem cells, Macrophages, Medical and Health Sciences, Immunology
Abstract

During emergency hematopoiesis, hematopoietic stem cells (HSCs) rapidly proliferate to produce myeloid and lymphoid effector cells, a response that is critical against infection or tissue injury. If unresolved, this process leads to sustained inflammation, which can cause life-threatening diseases and cancer. Here, we identify a role of double PHD fingers 2 (DPF2) in modulating inflammation. DPF2 is a defining subunit of the hematopoiesis-specific BAF (SWI/SNF) chromatin-remodeling complex, and it is mutated in multiple cancers and neurological disorders. We uncovered that hematopoiesis-specific Dpf2-KO mice developed leukopenia, severe anemia, and lethal systemic inflammation characterized by histiocytic and fibrotic tissue infiltration resembling a clinical hyperinflammatory state. Dpf2 loss impaired the polarization of macrophages responsible for tissue repair, induced the unrestrained activation of Th cells, and generated an emergency-like state of HSC hyperproliferation and myeloid cell-biased differentiation. Mechanistically, Dpf2 deficiency resulted in the loss of the BAF catalytic subunit BRG1 from nuclear factor erythroid 2-like 2-controlled (NRF2-controlled) enhancers, impairing the antioxidant and antiinflammatory transcriptional response needed to modulate inflammation. Finally, pharmacological reactivation of NRF2 suppressed the inflammation-mediated phenotypes and lethality of Dpf2Δ/Δ mice. Our work establishes an essential role of the DPF2-BAF complex in licensing NRF2-dependent gene expression in HSCs and immune effector cells to prevent chronic inflammation.

Published
2023

8. The status of the human gene catalogue

Author

Amaral, Paulo, Carbonell-Sala, Silvia, De La Vega, Francisco M., Faial, Tiago, Frankish, Adam, Gingeras, Thomas, Guigo, Roderic, Harrow, Jennifer L., Hatzigeorgiou, Artemis G., Johnson, Rory, Murphy, Terence D., Pertea, Mihaela, Pruitt, Kim D., Pujar, Shashikant, Takahashi, Hazuki, Ulitsky, Igor, Varabyou, Ales, Wells, Christine A., Yandell, Mark, Carninci, Piero, and Salzberg, Steven L.

Published
2023
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9. Correction: “The 5th edition of The World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms” Leukemia. 2022 Jul;36(7):1720–1748

Author

Alaggio, Rita, Amador, Catalina, Anagnostopoulos, Ioannis, Attygalle, Ayoma D., de Oliveira Araujo, Iguaracyra Barreto, Berti, Emilio, Bhagat, Govind, Borges, Anita Maria, Boyer, Daniel, Calaminici, Mariarita, Chadburn, Amy, Chan, John K. C., Cheuk, Wah, Chng, Wee-Joo, Choi, John K., Chuang, Shih-Sung, Coupland, Sarah E., Czader, Magdalena, Dave, Sandeep S., de Jong, Daphne, Di Napoli, Arianna, Du, Ming-Qing, Elenitoba-Johnson, Kojo S., Ferry, Judith, Geyer, Julia, Gratzinger, Dita, Guitart, Joan, Gujral, Sumeet, Harris, Marian, Harrison, Christine J., Hartmann, Sylvia, Hochhaus, Andreas, Jansen, Patty M., Karube, Kennosuke, Kempf, Werner, Khoury, Joseph, Kimura, Hiroshi, Klapper, Wolfram, Kovach, Alexandra E., Kumar, Shaji, Lazar, Alexander J., Lazzi, Stefano, Leoncini, Lorenzo, Leung, Nelson, Leventaki, Vasiliki, Li, Xiao-Qiu, Lim, Megan S., Liu, Wei-Ping, Louissaint, Jr, Abner, Marcogliese, Andrea, Medeiros, L. Jeffrey, Michal, Michael, Miranda, Roberto N., Mitteldorf, Christina, Montes-Moreno, Santiago, Morice, William, Nardi, Valentina, Naresh, Kikkeri N., Natkunam, Yasodha, Ng, Siok-Bian, Oschlies, Ilske, Ott, German, Parrens, Marie, Pulitzer, Melissa, Rajkumar, S. Vincent, Rawstron, Andrew C., Rech, Karen, Rosenwald, Andreas, Said, Jonathan, Sarkozy, Clémentine, Sayed, Shahin, Saygin, Caner, Schuh, Anna, Sewell, William, Siebert, Reiner, Sohani, Aliyah R., Suzuki, Ritsuro, Tooze, Reuben, Traverse-Glehen, Alexandra, Vega, Francisco, Vergier, Beatrice, Wechalekar, Ashutosh D., Wood, Brent, Xerri, Luc, and Xiao, Wenbin

Published
2023
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10. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms

Author

Alaggio, Rita, Amador, Catalina, Anagnostopoulos, Ioannis, Attygalle, Ayoma D, Araujo, Iguaracyra Barreto de Oliveira, Berti, Emilio, Bhagat, Govind, Borges, Anita Maria, Boyer, Daniel, Calaminici, Mariarita, Chadburn, Amy, Chan, John KC, Cheuk, Wah, Chng, Wee-Joo, Choi, John K, Chuang, Shih-Sung, Coupland, Sarah E, Czader, Magdalena, Dave, Sandeep S, de Jong, Daphne, Du, Ming-Qing, Elenitoba-Johnson, Kojo S, Ferry, Judith, Geyer, Julia, Gratzinger, Dita, Guitart, Joan, Gujral, Sumeet, Harris, Marian, Harrison, Christine J, Hartmann, Sylvia, Hochhaus, Andreas, Jansen, Patty M, Karube, Kennosuke, Kempf, Werner, Khoury, Joseph, Kimura, Hiroshi, Klapper, Wolfram, Kovach, Alexandra E, Kumar, Shaji, Lazar, Alexander J, Lazzi, Stefano, Leoncini, Lorenzo, Leung, Nelson, Leventaki, Vasiliki, Li, Xiao-Qiu, Lim, Megan S, Liu, Wei-Ping, Louissaint, Abner, Marcogliese, Andrea, Medeiros, L Jeffrey, Michal, Michael, Miranda, Roberto N, Mitteldorf, Christina, Montes-Moreno, Santiago, Morice, William, Nardi, Valentina, Naresh, Kikkeri N, Natkunam, Yasodha, Ng, Siok-Bian, Oschlies, Ilske, Ott, German, Parrens, Marie, Pulitzer, Melissa, Rajkumar, S Vincent, Rawstron, Andrew C, Rech, Karen, Rosenwald, Andreas, Said, Jonathan, Sarkozy, Clémentine, Sayed, Shahin, Saygin, Caner, Schuh, Anna, Sewell, William, Siebert, Reiner, Sohani, Aliyah R, Tooze, Reuben, Traverse-Glehen, Alexandra, Vega, Francisco, Vergier, Beatrice, Wechalekar, Ashutosh D, Wood, Brent, Xerri, Luc, and Xiao, Wenbin

Subjects
Cancer, Hematologic Neoplasms, Humans, Lymphoma, World Health Organization, Clinical Sciences, Oncology and Carcinogenesis, Immunology
Abstract

We herein present an overview of the upcoming 5th edition of the World Health Organization Classification of Haematolymphoid Tumours focussing on lymphoid neoplasms. Myeloid and histiocytic neoplasms will be presented in a separate accompanying article. Besides listing the entities of the classification, we highlight and explain changes from the revised 4th edition. These include reorganization of entities by a hierarchical system as is adopted throughout the 5th edition of the WHO classification of tumours of all organ systems, modification of nomenclature for some entities, revision of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities, as well as inclusion of tumour-like lesions, mesenchymal lesions specific to lymph node and spleen, and germline predisposition syndromes associated with the lymphoid neoplasms.

Published
2022

12. Upper Cretaceous Crustacea from Central Cuba

Author

Vega, Francisco J., Nyborg, Torrey, Garassino, Alessandro, Pasini, Giovanni, Aguilar-Pérez, Javier, Borges-Sellén, Carlos R., Arano-Ruiz, Alberto F., Quintero-Vázquez, Servilio J., and Gutiérrez-Domech, Roberto Manuel

Published
2024
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14. An open-source, automated, and cost-effective platform for COVID-19 diagnosis and rapid portable genomic surveillance using nanopore sequencing

Author

Ramos-Mandujano, Gerardo, Grünberg, Raik, Zhang, Yingzi, Bi, Chongwei, Guzmán-Vega, Francisco J., Shuaib, Muhammad, Gorchakov, Rodion V., Xu, Jinna, Tehseen, Muhammad, Takahashi, Masateru, Takahashi, Etsuko, Dada, Ashraf, Ahmad, Adeel Nazir, Hamdan, Samir M., Pain, Arnab, Arold, Stefan T., and Li, Mo

Published
2023
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16. Molecular profiling of a real-world breast cancer cohort with genetically inferred ancestries reveals actionable tumor biology differences between European ancestry and African ancestry patient populations

Author

Miyashita, Minoru, Bell, Joshua S. K., Wenric, Stephane, Karaesmen, Ezgi, Rhead, Brooke, Kase, Matthew, Kaneva, Kristiyana, De La Vega, Francisco M., Zheng, Yonglan, Yoshimatsu, Toshio F., Khramtsova, Galina, Liu, Fang, Zhao, Fangyuan, Howard, Frederick M., Nanda, Rita, Beaubier, Nike, White, Kevin P., Huo, Dezheng, and Olopade, Olufunmilayo I.

Published
2023
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20. SMARCA4 is a haploinsufficient B cell lymphoma tumor suppressor that fine-tunes centrocyte cell fate decisions

Author

Deng, Qing, Lakra, Priya, Gou, Panhong, Yang, Haopeng, Meydan, Cem, Teater, Matthew, Chin, Christopher, Zhang, Wenchao, Dinh, Tommy, Hussein, Usama, Li, Xubin, Rojas, Estela, Liu, Weiguang, Reville, Patrick K., Kizhakeyil, Atish, Barisic, Darko, Parsons, Sydney, Wilson, Ashley, Henderson, Jared, Scull, Brooks, Gurumurthy, Channabasavaiah, Vega, Francisco, Chadburn, Amy, Cuglievan, Branko, El-Mallawany, Nader Kim, Allen, Carl, Mason, Christopher, Melnick, Ari, and Green, Michael R.

Published
2024
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25. An automated 13.5 hour system for scalable diagnosis and acute management guidance for genetic diseases

Author

Owen, Mallory J, Lefebvre, Sebastien, Hansen, Christian, Kunard, Chris M, Dimmock, David P, Smith, Laurie D, Scharer, Gunter, Mardach, Rebecca, Willis, Mary J, Feigenbaum, Annette, Niemi, Anna-Kaisa, Ding, Yan, Van Der Kraan, Luca, Ellsworth, Katarzyna, Guidugli, Lucia, Lajoie, Bryan R, McPhail, Timothy K, Mehtalia, Shyamal S, Chau, Kevin K, Kwon, Yong H, Zhu, Zhanyang, Batalov, Sergey, Chowdhury, Shimul, Rego, Seema, Perry, James, Speziale, Mark, Nespeca, Mark, Wright, Meredith S, Reese, Martin G, De La Vega, Francisco M, Azure, Joe, Frise, Erwin, Rigby, Charlene Son, White, Sandy, Hobbs, Charlotte A, Gilmer, Sheldon, Knight, Gail, Oriol, Albert, Lenberg, Jerica, Nahas, Shareef A, Perofsky, Kate, Kim, Kyu, Carroll, Jeanne, Coufal, Nicole G, Sanford, Erica, Wigby, Kristen, Weir, Jacqueline, Thomson, Vicki S, Fraser, Louise, Lazare, Seka S, Shin, Yoon H, Grunenwald, Haiying, Lee, Richard, Jones, David, Tran, Duke, Gross, Andrew, Daigle, Patrick, Case, Anne, Lue, Marisa, Richardson, James A, Reynders, John, Defay, Thomas, Hall, Kevin P, Veeraraghavan, Narayanan, and Kingsmore, Stephen F

Subjects
Human Genome, Pediatric, Genetics, Biotechnology, Pediatric Research Initiative, Good Health and Well Being, Child, DNA Copy Number Variations, Humans, Infant, Retrospective Studies, Whole Genome Sequencing
Abstract

While many genetic diseases have effective treatments, they frequently progress rapidly to severe morbidity or mortality if those treatments are not implemented immediately. Since front-line physicians frequently lack familiarity with these diseases, timely molecular diagnosis may not improve outcomes. Herein we describe Genome-to-Treatment, an automated, virtual system for genetic disease diagnosis and acute management guidance. Diagnosis is achieved in 13.5 h by expedited whole genome sequencing, with superior analytic performance for structural and copy number variants. An expert panel adjudicated the indications, contraindications, efficacy, and evidence-of-efficacy of 9911 drug, device, dietary, and surgical interventions for 563 severe, childhood, genetic diseases. The 421 (75%) diseases and 1527 (15%) effective interventions retained are integrated with 13 genetic disease information resources and appended to diagnostic reports ( https://gtrx.radygenomiclab.com ). This system provided correct diagnoses in four retrospectively and two prospectively tested infants. The Genome-to-Treatment system facilitates optimal outcomes in children with rapidly progressive genetic diseases.

Published
2022

27. Evolutionary characterization of lung adenocarcinoma morphology in TRACERx

Author

Karasaki, Takahiro, Moore, David A., Veeriah, Selvaraju, Naceur-Lombardelli, Cristina, Toncheva, Antonia, Magno, Neil, Ward, Sophia, Bakir, Maise Al, Watkins, Thomas B. K., Grigoriadis, Kristiana, Huebner, Ariana, Hill, Mark S., Frankell, Alexander M., Abbosh, Christopher, Puttick, Clare, Zhai, Haoran, Gimeno-Valiente, Francisco, Saghafinia, Sadegh, Kanu, Nnennaya, Dietzen, Michelle, Pich, Oriol, Lim, Emilia L., Martínez-Ruiz, Carlos, Black, James R. M., Biswas, Dhruva, Campbell, Brittany B., Lee, Claudia, Colliver, Emma, Enfield, Katey S. S., Hessey, Sonya, Hiley, Crispin T., Zaccaria, Simone, Litchfield, Kevin, Birkbak, Nicolai J., Cadieux, Elizabeth Larose, Demeulemeester, Jonas, Van Loo, Peter, Adusumilli, Prasad S., Tan, Kay See, Cheema, Waseem, Sanchez-Vega, Francisco, Jones, David R., Rekhtman, Natasha, Travis, William D., Hackshaw, Allan, Marafioti, Teresa, Salgado, Roberto, Le Quesne, John, Nicholson, Andrew G., McGranahan, Nicholas, Swanton, Charles, and Jamal-Hanjani, Mariam

Published
2023
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28. Impact of cumulative dose of brentuximab vedotin on outcomes of frontline therapy for advanced-stage Hodgkin lymphoma

Author

Steiner, Raphael E., Hwang, Steven R., Khurana, Arushi, Habermann, Thomas M., Epperla, Narendranath, Annunzio, Kaitlin, Allen, Pamela Blair, Baird, Katelin, Paulino, Darina, Alderuccio, Juan Pablo, Lossos, Izidore S., David, Kevin, Evens, Andrew M., Pandya, Karan, Bair, Steven M., Kamdar, Manali, Ba Aqeel, Sheeba, Torka, Pallawi, Lynch, Ryan, Smith, Stephen, Feng, Lei, Noorani, Mansoor, Ahmed, Sairah, Nair, Ranjit, Vega, Francisco, Wu, Susan, Fang, Penny, Pinnix, Chelsea C., Gunther, Jillian R., Dabaja, Bouthaina S., and Lee, Hun J.

Published
2023
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31. The Baf Subunit Dpf2 Regulates Resolution of Inflammation By Controlling Macrophage Differentiation Transcription Factor Networks

Author

Mas Martin, Gloria, Man, Na, Karl, Daniel, Martinez, Concepcion, Duffort, Stephanie, Itonaga, Hidehiro, Mookhtiar, Adnan K, Bilbao, Daniel, Kunkalla, Kranthi, Valencia, Alfredo M, Collings, Clayton, Kadoch, Cigall, Vega, Francisco, Kogan, Scott C, and Nimer, Stephen

Subjects
Rare Diseases, Stem Cell Research, Stem Cell Research - Nonembryonic - Non-Human, Hematology, Genetics, Cancer, Biotechnology, Regenerative Medicine, Aetiology, 2.1 Biological and endogenous factors, Underpinning research, 1.1 Normal biological development and functioning, Inflammatory and immune system, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Paediatrics and Reproductive Medicine, Immunology
Abstract

To mount an effective immune response against infectious pathogens or tissue injury, hematopoietic stem cells (HSCs) increase their proliferation and production of myeloid cells, including macrophages, which destroy the pathogens and repair the damaged tissue. Proper resolution of inflammation is essential to restore hematopoietic homeostasis, as unrestrained inflammation can result in life-threatening pathologies such as sepsis, autoimmune disorders and cancer. The molecular mechanisms that control the resolution of inflammation, and how these contribute to disease phenotypes, are poorly understood. BAF (SWI/SNF) complexes are ATPase dependent chromatin-remodeling complexes that play fundamental roles in transcription. BAF complexes use the energy of ATP to modulate the accessibility of transcription factors to DNA and thus, orchestrate the gene expression programs that control proliferation and cellular identity. Genes encoding for BAF subunits are frequently mutated in cancer and developmental disorders. In hematopoietic malignancies, loss-of-function mutations and low expression of specific BAF subunits have been reported in patients with anemia and bone marrow failure. Work from our lab previously demonstrated that the hematopoietic-specific BAF complex subunit Dpf2 cooperates with the transcription factor Runx1 to regulate myeloid differentiation. Based on these studies, we generated a hematopoietic-specific Dpf2 knock-out mouse model and found that mice lacking Dpf2 develop pancytopenia, anemia and an uncontrolled inflammatory response that results in early death. Dpf2-/- peripheral blood samples showed dysplastic features including increased number of polychromatophilic blood cells and Howell-Jolly bodies in erythrocytes. Histopathological analyses revealed the presence of fibrosis and prominent infiltration of histiocytes in multiple organs, including lungs, liver and spleen. Detailed chemical profiling of plasma showed increased levels of multiple pro-inflammatory cytokines, indicative of systemic inflammation. Flow cytometry analyses and Mass cytometry profiling further revealed an expansion of myeloid lineages, specifically monocytes and macrophages, concomitant with severe defects in lymphoid and erythroid differentiation. We also found that Dpf2-/-HSCs had increased serial re-plating capacity and a marked myeloid differentiation bias. To identify the transcription factor networks underlying these phenotypes, we performed RNAseq and ATACseq on control and Dpf2-/- HSCs. Gene Set Enrichment Analyses indicated that Dpf2-/- HSCs have extensive gene expression alterations in immune signaling and interferon response pathways, as well as leukocyte and erythroid differentiation. We also found that Dpf2 loss results in pronounced changes in expression and genomic accessibility of specific transcription factors that control macrophage differentiation and proliferation. Together, our mechanistic studies support a model whereby the absence of Dpf2 results in misregulation of the transcription factor networks that establish macrophage cell identity, leading to a marked increase in macrophage infiltrations and shortened survival of the mice. Treatment of the Dpf2-/-mice with clodronate-containing liposomes, which deplete macrophages from bone marrow and spleen, prolonged survival of the mice. Our work uncovers a novel role of Dpf2 in restraining inflammatory responses by controlling macrophage proliferation and function. Moreover, we propose that, in addition to their tumor suppressive roles in cancer, BAF complexes may have a central role in the prevention of immunopathologies. Disclosures Kadoch: Foghorn Therapeutics: Consultancy, Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Other: Scientific founder, fiduciary board of directors member, scientific advisory board member, shareholder, and consultant for Foghorn Therapeutics (Cambridge, MA). . Vega:NCI: Research Funding.

Published
2020

32. Genomic Predictors of Recurrence Patterns After Complete Resection of Colorectal Liver Metastases and Adjuvant Hepatic Artery Infusion Chemotherapy

Author

Narayan, Raja R., Datta, Jashodeep, Goldman, Debra A., Aveson, Victoria G., Walch, Henry S., Sanchez-Vega, Francisco, Gönen, Mithat, Balachandran, Vinod P., Drebin, Jeffrey A., Jarnagin, William R., Kingham, T. Peter, Wei, Alice C., Schultz, Nikolaus, Kemeny, Nancy E., and D’Angelica, Michael I.

Published
2022
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33. Genomic mapping of metastatic organotropism in lung adenocarcinoma

Author

Lengel, Harry B., Mastrogiacomo, Brooke, Connolly, James G., Tan, Kay See, Liu, Yuan, Fick, Cameron N., Dunne, Elizabeth G., He, Di, Lankadasari, Manendra B., Satravada, Baby Anusha, Sun, Yichao, Kundra, Ritika, Fong, Chris, Smith, Shaleigh, Riely, Gregory J., Rudin, Charles M., Gomez, Daniel R., Solit, David B., Berger, Michael F., Li, Bob T., Mayo, Marty W., Matei, Irina, Lyden, David C., Adusumilli, Prasad S., Schultz, Nikolaus, Sanchez-Vega, Francisco, and Jones, David R.

Published
2023
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34. Interleukin-26 activates macrophages and facilitates killing of Mycobacterium tuberculosis.

Author

Hawerkamp, Heike C, van Geelen, Lasse, Korte, Jan, Di Domizio, Jeremy, Swidergall, Marc, Momin, Afaque A, Guzmán-Vega, Francisco J, Arold, Stefan T, Ernst, Joachim, Gilliet, Michel, Kalscheuer, Rainer, Homey, Bernhard, and Meller, Stephan

Subjects
Dendritic Cells, Leukocytes, Mononuclear, Cell Line, Macrophages, Humans, Mycobacterium tuberculosis, Tuberculosis, Tumor Necrosis Factor-alpha, RNA, Messenger, Interleukins, Cytokines, Adult, Aged, Middle Aged, Female, Male, HEK293 Cells, THP-1 Cells
Abstract

Tuberculosis-causing Mycobacterium tuberculosis (Mtb) is transmitted via airborne droplets followed by a primary infection of macrophages and dendritic cells. During the activation of host defence mechanisms also neutrophils and T helper 1 (TH1) and TH17 cells are recruited to the site of infection. The TH17 cell-derived interleukin (IL)-17 in turn induces the cathelicidin LL37 which shows direct antimycobacterial effects. Here, we investigated the role of IL-26, a TH1- and TH17-associated cytokine that exhibits antimicrobial activity. We found that both IL-26 mRNA and protein are strongly increased in tuberculous lymph nodes. Furthermore, IL-26 is able to directly kill Mtb and decrease the infection rate in macrophages. Binding of IL-26 to lipoarabinomannan might be one important mechanism in extracellular killing of Mtb. Macrophages and dendritic cells respond to IL-26 with secretion of tumor necrosis factor (TNF)-α and chemokines such as CCL20, CXCL2 and CXCL8. In dendritic cells but not in macrophages cytokine induction by IL-26 is partly mediated via Toll like receptor (TLR) 2. Taken together, IL-26 strengthens the defense against Mtb in two ways: firstly, directly due to its antimycobacterial properties and secondly indirectly by activating innate immune mechanisms.

Published
2020

35. Pan-cancer analysis of whole genomes

Author

Campbell, Peter J, Getz, Gad, Korbel, Jan O, Stuart, Joshua M, Jennings, Jennifer L, Stein, Lincoln D, Perry, Marc D, Nahal-Bose, Hardeep K, Ouellette, BF Francis, Li, Constance H, Rheinbay, Esther, Nielsen, G Petur, Sgroi, Dennis C, Wu, Chin-Lee, Faquin, William C, Deshpande, Vikram, Boutros, Paul C, Lazar, Alexander J, Hoadley, Katherine A, Louis, David N, Dursi, L Jonathan, Yung, Christina K, Bailey, Matthew H, Saksena, Gordon, Raine, Keiran M, Buchhalter, Ivo, Kleinheinz, Kortine, Schlesner, Matthias, Zhang, Junjun, Wang, Wenyi, Wheeler, David A, Ding, Li, Simpson, Jared T, O'Connor, Brian D, Yakneen, Sergei, Ellrott, Kyle, Miyoshi, Naoki, Butler, Adam P, Royo, Romina, Shorser, Solomon I, Vazquez, Miguel, Rausch, Tobias, Tiao, Grace, Waszak, Sebastian M, Rodriguez-Martin, Bernardo, Shringarpure, Suyash, Wu, Dai-Ying, Demidov, German M, Delaneau, Olivier, Hayashi, Shuto, Imoto, Seiya, Habermann, Nina, Segre, Ayellet V, Garrison, Erik, Cafferkey, Andy, Alvarez, Eva G, Maria Heredia-Genestar, Jose, Muyas, Francesc, Drechsel, Oliver, Bruzos, Alicia L, Temes, Javier, Zamora, Jorge, Baez-Ortega, Adrian, Kim, Hyung-Lae, Mashl, R Jay, Ye, Kai, DiBiase, Anthony, Huang, Kuan-lin, Letunic, Ivica, McLellan, Michael D, Newhouse, Steven J, Shmaya, Tal, Kumar, Sushant, Wedge, David C, Wright, Mark H, Yellapantula, Venkata D, Gerstein, Mark, Khurana, Ekta, Marques-Bonet, Tomas, Navarro, Arcadi, Bustamante, Carlos D, Siebert, Reiner, Nakagawa, Hidewaki, Easton, Douglas F, Ossowski, Stephan, Tubio, Jose MC, De La Vega, Francisco M, Estivill, Xavier, Yuen, Denis, Mihaiescu, George L, Omberg, Larsson, Ferretti, Vincent, Sabarinathan, Radhakrishnan, Pich, Oriol, Gonzalez-Perez, Abel, Weiner, Amaro Taylor, Fittall, Matthew W, Demeulemeester, Jonas, Tarabichi, Maxime, and Roberts, Nicola D

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Bioinformatics and Computational Biology, Genetics, Oncology and Carcinogenesis, Cancer Genomics, Biotechnology, Human Genome, Cancer, Prevention, 2.1 Biological and endogenous factors, Cell Proliferation, Cellular Senescence, Chromothripsis, Cloud Computing, DNA Mutational Analysis, Evolution, Molecular, Female, Genome, Human, Genomics, Germ-Line Mutation, High-Throughput Nucleotide Sequencing, Humans, Information Dissemination, Male, Mutagenesis, Mutation, Neoplasms, Oncogenes, Promoter Regions, Genetic, RNA Splicing, Reproducibility of Results, Telomerase, Telomere, ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium, General Science & Technology
Abstract

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1-3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10-18.

Published
2020

36. Early TP53 alterations engage environmental exposures to promote gastric premalignancy in an integrative mouse model.

Author

Sethi, Nilay S, Kikuchi, Osamu, Duronio, Gina N, Stachler, Matthew D, McFarland, James M, Ferrer-Luna, Ruben, Zhang, Yanxi, Bao, Chunyang, Bronson, Roderick, Patil, Deepa, Sanchez-Vega, Francisco, Liu, Jie-Bin, Sicinska, Ewa, Lazaro, Jean-Bernard, Ligon, Keith L, Beroukhim, Rameen, and Bass, Adam J

Subjects
Organoids, Cell Line, Tumor, Animals, Mice, Inbred C57BL, Mice, Transgenic, Mice, Knockout, Humans, Adenocarcinoma, Esophageal Neoplasms, Stomach Neoplasms, Neoplasms, Experimental, Precancerous Conditions, Barrett Esophagus, Methylnitrosourea, Environmental Exposure, Mutation, Tumor Suppressor Protein p53, Cyclin-Dependent Kinase Inhibitor p16, Cell Line, Tumor, Mice, Inbred C57BL, Transgenic, Knockout, Neoplasms, Experimental, Developmental Biology, Biological Sciences, Medical and Health Sciences
Abstract

Somatic alterations in cancer genes are being detected in normal and premalignant tissue, thus placing greater emphasis on gene-environment interactions that enable disease phenotypes. By combining early genetic alterations with disease-relevant exposures, we developed an integrative mouse model to study gastric premalignancy. Deletion of Trp53 in gastric cells confers a selective advantage and promotes the development of dysplasia in the setting of dietary carcinogens. Organoid derivation from dysplastic lesions facilitated genomic, transcriptional and functional evaluation of gastric premalignancy. Cell cycle regulators, most notably Cdkn2a, were upregulated by p53 inactivation in gastric premalignancy, serving as a barrier to disease progression. Co-deletion of Cdkn2a and Trp53 in dysplastic gastric organoids promoted cancer phenotypes but also induced replication stress, exposing a susceptibility to DNA damage response inhibitors. These findings demonstrate the utility of mouse models that integrate genomic alterations with relevant exposures and highlight the importance of gene-environment interactions in shaping the premalignant state.

Published
2020

38. A phase 1/2 study of lenalidomide and obinutuzumab with CHOP for newly diagnosed DLBCL

Author

Cherng, Hua-Jay J., Alig, Stefan K., Oki, Yasuhiro, Nastoupil, Loretta J., Fayad, Luis, Neelapu, Sattva S., Turturro, Francesco, Hagemeister, Fredrick, Craig, Alexander F. M., Macaulay, Charles W., Rodriguez, Maria Alma, Lee, Hun Ju, McDonnell, Timothy J., Flowers, Christopher R., Vega, Francisco, Green, Michael R., Feng, Lei, Kurtz, David M., Alizadeh, Ash A., Davis, R. Eric, and Westin, Jason R.

Published
2023
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42. Genomic and transcriptomic determinants of response to neoadjuvant therapy in rectal cancer

Author

Chatila, Walid K., Kim, Jin K., Walch, Henry, Marco, Michael R., Chen, Chin-Tung, Wu, Fan, Omer, Dana M., Khalil, Danny N., Ganesh, Karuna, Qu, Xuan, Luthra, Anisha, Choi, Seo-Hyun, Ho, Yu-Jui, Kundra, Ritika, Groves, Katharine I., Chow, Oliver S., Cercek, Andrea, Weiser, Martin R., Widmar, Maria, Wei, Iris H., Pappou, Emmanouil P., Nash, Garrett M., Paty, Philip B., Shi, Qian, Vakiani, Efsevia, Duygu Selcuklu, S., Donoghue, Mark T. A., Solit, David B., Berger, Michael F., Shia, Jinru, Pelossof, Raphael, Romesser, Paul B., Yaeger, Rona, Smith, J. Joshua, Schultz, Nikolaus, Sanchez-Vega, Francisco, and Garcia-Aguilar, Julio

Published
2022
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47. Best practices for benchmarking germline small-variant calls in human genomes

Author

Krusche, Peter, Trigg, Len, Boutros, Paul C, Mason, Christopher E, De La Vega, Francisco M, Moore, Benjamin L, Gonzalez-Porta, Mar, Eberle, Michael A, Tezak, Zivana, Lababidi, Samir, Truty, Rebecca, Asimenos, George, Funke, Birgit, Fleharty, Mark, Chapman, Brad A, Salit, Marc, and Zook, Justin M

Subjects
Biological Sciences, Genetics, Clinical Research, Human Genome, Generic health relevance, Algorithms, Benchmarking, Exome, Genome, Human, Genomics, Germ Cells, High-Throughput Nucleotide Sequencing, Humans, Polymorphism, Single Nucleotide, Software, Global Alliance for Genomics and Health Benchmarking Team
Abstract

Standardized benchmarking approaches are required to assess the accuracy of variants called from sequence data. Although variant-calling tools and the metrics used to assess their performance continue to improve, important challenges remain. Here, as part of the Global Alliance for Genomics and Health (GA4GH), we present a benchmarking framework for variant calling. We provide guidance on how to match variant calls with different representations, define standard performance metrics, and stratify performance by variant type and genome context. We describe limitations of high-confidence calls and regions that can be used as truth sets (for example, single-nucleotide variant concordance of two methods is 99.7% inside versus 76.5% outside high-confidence regions). Our web-based app enables comparison of variant calls against truth sets to obtain a standardized performance report. Our approach has been piloted in the PrecisionFDA variant-calling challenges to identify the best-in-class variant-calling methods within high-confidence regions. Finally, we recommend a set of best practices for using our tools and evaluating the results.

Published
2019

48. Integrative Molecular Characterization of Malignant Pleural Mesothelioma

Author

Hmeljak, Julija, Sanchez-Vega, Francisco, Hoadley, Katherine A, Shih, Juliann, Stewart, Chip, Heiman, David, Tarpey, Patrick, Danilova, Ludmila, Drill, Esther, Gibb, Ewan A, Bowlby, Reanne, Kanchi, Rupa, Osmanbeyoglu, Hatice U, Sekido, Yoshitaka, Takeshita, Jumpei, Newton, Yulia, Graim, Kiley, Gupta, Manaswi, Gay, Carl M, Diao, Lixia, Gibbs, David L, Thorsson, Vesteinn, Iype, Lisa, Kantheti, Havish, Severson, David T, Ravegnini, Gloria, Desmeules, Patrice, Jungbluth, Achim A, Travis, William D, Dacic, Sanja, Chirieac, Lucian R, Galateau-Sallé, Françoise, Fujimoto, Junya, Husain, Aliya N, Silveira, Henrique C, Rusch, Valerie W, Rintoul, Robert C, Pass, Harvey, Kindler, Hedy, Zauderer, Marjorie G, Kwiatkowski, David J, Bueno, Raphael, Tsao, Anne S, Creaney, Jenette, Lichtenberg, Tara, Leraas, Kristen, Bowen, Jay, Felau, Ina, Zenklusen, Jean Claude, Akbani, Rehan, Cherniack, Andrew D, Byers, Lauren A, Noble, Michael S, Fletcher, Jonathan A, Robertson, A Gordon, Shen, Ronglai, Aburatani, Hiroyuki, Robinson, Bruce W, Campbell, Peter, Ladanyi, Marc, Ally, Adrian, Anur, Pavana, Armenia, Joshua, Auman, J Todd, Balasundaram, Miruna, Balu, Saianand, Baylin, Stephen B, Becich, Michael, Behrens, Carmen, Beroukhim, Rameen, Bielski, Craig, Bodenheimer, Tom, Bootwalla, Moiz S, Brooks, Denise, Byers, Lauren Averett, Cárcano, Flávio M, Carlsen, Rebecca, Carvalho, Andre L, Cheung, Dorothy, Chirieac, Lucian, Cho, Juok, Chuah, Eric, Chudamani, Sudha, Cibulskis, Carrie, Cope, Leslie, Crain, Daniel, Curley, Erin, Rienzo, Assunta De, DeFreitas, Timothy, Demchok, John A, and Dhalla, Noreen

Subjects
Rare Diseases, Lung Cancer, Biotechnology, Lung, Cancer, Human Genome, Genetics, 2.1 Biological and endogenous factors, Aetiology, Good Health and Well Being, Aged, Biomarkers, Tumor, Female, Histone-Lysine N-Methyltransferase, Humans, Kaplan-Meier Estimate, Lung Neoplasms, Male, Mesothelioma, Middle Aged, Mutation, Pleural Neoplasms, Prognosis, Protein Methyltransferases, Tumor Suppressor Proteins, Ubiquitin Thiolesterase, TCGA Research Network, Oncology and Carcinogenesis
Abstract

Malignant pleural mesothelioma (MPM) is a highly lethal cancer of the lining of the chest cavity. To expand our understanding of MPM, we conducted a comprehensive integrated genomic study, including the most detailed analysis of BAP1 alterations to date. We identified histology-independent molecular prognostic subsets, and defined a novel genomic subtype with TP53 and SETDB1 mutations and extensive loss of heterozygosity. We also report strong expression of the immune-checkpoint gene VISTA in epithelioid MPM, strikingly higher than in other solid cancers, with implications for the immune response to MPM and for its immunotherapy. Our findings highlight new avenues for further investigation of MPM biology and novel therapeutic options. SIGNIFICANCE: Through a comprehensive integrated genomic study of 74 MPMs, we provide a deeper understanding of histology-independent determinants of aggressive behavior, define a novel genomic subtype with TP53 and SETDB1 mutations and extensive loss of heterozygosity, and discovered strong expression of the immune-checkpoint gene VISTA in epithelioid MPM.See related commentary by Aggarwal and Albelda, p. 1508.This article is highlighted in the In This Issue feature, p. 1494.

Published
2018

50. Intraoperative opioids are associated with decreased recurrence rates in colon adenocarcinoma: a retrospective observational cohort study

Author

Yuval, Jonathan B., Lee, Jasme, Wu, Fan, Thompson, Hannah M., Verheij, Floris S., Gupta, Hersh V., Irie, Takeshi, Scarpa, Joseph R., McCormick, Patrick J., Smith, J. Joshua, Shia, Jinru, Weiser, Martin R., Sánchez-Vega, Francisco, Tan, Kay See, Fischer, Gregory W., Garcia-Aguilar, Julio, and Mincer, Joshua S.

Published
2022
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