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203 results on '"Malta, Tathiane M."'

1. Haploinsufficiency of NFKBIA reshapes the epigenome antipodal to the IDH mutation and imparts disease fate in diffuse gliomas

Author

Bredel, Markus, Espinosa, Lluís, Kim, Hyunsoo, Scholtens, Denise M, McElroy, Joseph P, Rajbhandari, Rajani, Meng, Wei, Kollmeyer, Thomas M, Malta, Tathiane M, Quezada, Michael A, Harsh, Griffith R, Lobo-Jarne, Teresa, Solé, Laura, Merati, Aran, Nagaraja, Surya, Nair, Sindhu, White, Jaclyn J, Thudi, Nanda K, Fleming, Jessica L, Webb, Amy, Natsume, Atsushi, Ogawa, Seishi, Weber, Ruthild G, Bertran, Joan, Haque, S Jaharul, Hentschel, Bettina, Miller, C Ryan, Furnari, Frank B, Chan, Timothy A, Grosu, Anca-Ligia, Weller, Michael, Barnholtz-Sloan, Jill S, Monje, Michelle, Noushmehr, Houtan, Jenkins, Robert B, Rogers, C Leland, MacDonald, David R, Pugh, Stephanie L, and Chakravarti, Arnab

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Rare Diseases, Orphan Drug, Genetics, Brain Disorders, Brain Cancer, Human Genome, Child, Humans, Brain Neoplasms, Epigenome, Glioma, Haploinsufficiency, Mutation, NF-KappaB Inhibitor alpha, Isocitrate Dehydrogenase, H3K27M mutation, IDH mutation, NFKBIA deletion, glioma, haploinsufficiency, methylome, nomogram, tumor suppressor, Biomedical and clinical sciences
Abstract

Genetic alterations help predict the clinical behavior of diffuse gliomas, but some variability remains uncorrelated. Here, we demonstrate that haploinsufficient deletions of chromatin-bound tumor suppressor NFKB inhibitor alpha (NFKBIA) display distinct patterns of occurrence in relation to other genetic markers and are disproportionately present at recurrence. NFKBIA haploinsufficiency is associated with unfavorable patient outcomes, independent of genetic and clinicopathologic predictors. NFKBIA deletions reshape the DNA and histone methylome antipodal to the IDH mutation and induce a transcriptome landscape partly reminiscent of H3K27M mutant pediatric gliomas. In IDH mutant gliomas, NFKBIA deletions are common in tumors with a clinical course similar to that of IDH wild-type tumors. An externally validated nomogram model for estimating individual patient survival in IDH mutant gliomas confirms that NFKBIA deletions predict comparatively brief survival. Thus, NFKBIA haploinsufficiency aligns with distinct epigenome changes, portends a poor prognosis, and should be incorporated into models predicting the disease fate of diffuse gliomas.

Published
2023

2. Glioma progression is shaped by genetic evolution and microenvironment interactions

Author

Varn, Frederick S, Johnson, Kevin C, Martinek, Jan, Huse, Jason T, Nasrallah, MacLean P, Wesseling, Pieter, Cooper, Lee AD, Malta, Tathiane M, Wade, Taylor E, Sabedot, Thais S, Brat, Daniel, Gould, Peter V, Wöehrer, Adelheid, Aldape, Kenneth, Ismail, Azzam, Sivajothi, Santhosh K, Barthel, Floris P, Kim, Hoon, Kocakavuk, Emre, Ahmed, Nazia, White, Kieron, Datta, Indrani, Moon, Hyo-Eun, Pollock, Steven, Goldfarb, Christine, Lee, Ga-Hyun, Garofano, Luciano, Anderson, Kevin J, Nehar-Belaid, Djamel, Barnholtz-Sloan, Jill S, Bakas, Spyridon, Byrne, Annette T, D’Angelo, Fulvio, Gan, Hui K, Khasraw, Mustafa, Migliozzi, Simona, Ormond, D Ryan, Paek, Sun Ha, Van Meir, Erwin G, Walenkamp, Annemiek ME, Watts, Colin, Weiss, Tobias, Weller, Michael, Palucka, Karolina, Stead, Lucy F, Poisson, Laila M, Noushmehr, Houtan, Iavarone, Antonio, Verhaak, Roel GW, Consortium, The GLASS, Alfaro, Kristin D, Amin, Samirkumar B, Ashley, David M, Bock, Christoph, Brodbelt, Andrew, Bulsara, Ketan R, and Castro, Ana Valeria

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Rare Diseases, Brain Disorders, Brain Cancer, Genetics, Cancer, Neurosciences, 2.1 Biological and endogenous factors, Aetiology, Adult, Brain Neoplasms, Evolution, Molecular, Genes, p16, Glioma, Humans, Isocitrate Dehydrogenase, Mutation, Neoplasm Recurrence, Local, Tumor Microenvironment, GLASS Consortium, genomics, glioblastoma, glioma, hypermutation, macrophages, microenvironment, neurons, single-cell, spatial imaging, treatment resistance, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

The factors driving therapy resistance in diffuse glioma remain poorly understood. To identify treatment-associated cellular and genetic changes, we analyzed RNA and/or DNA sequencing data from the temporally separated tumor pairs of 304 adult patients with isocitrate dehydrogenase (IDH)-wild-type and IDH-mutant glioma. Tumors recurred in distinct manners that were dependent on IDH mutation status and attributable to changes in histological feature composition, somatic alterations, and microenvironment interactions. Hypermutation and acquired CDKN2A deletions were associated with an increase in proliferating neoplastic cells at recurrence in both glioma subtypes, reflecting active tumor growth. IDH-wild-type tumors were more invasive at recurrence, and their neoplastic cells exhibited increased expression of neuronal signaling programs that reflected a possible role for neuronal interactions in promoting glioma progression. Mesenchymal transition was associated with the presence of a myeloid cell state defined by specific ligand-receptor interactions with neoplastic cells. Collectively, these recurrence-associated phenotypes represent potential targets to alter disease progression.

Published
2022

4. Detection of diagnostic and prognostic methylation-based signatures in liquid biopsy specimens from patients with meningiomas

Author

Herrgott, Grayson A., Snyder, James M., She, Ruicong, Malta, Tathiane M., Sabedot, Thais S., Lee, Ian Y., Pawloski, Jacob, Podolsky-Gondim, Guilherme G., Asmaro, Karam P., Zhang, Jiaqi, Cannella, Cara E., Nelson, Kevin, Thomas, Bartow, deCarvalho, Ana C., Hasselbach, Laura A., Tundo, Kelly M., Newaz, Rehnuma, Transou, Andrea, Morosini, Natalia, Francisco, Victor, Poisson, Laila M., Chitale, Dhananjay, Mukherjee, Abir, Mosella, Maritza S., Robin, Adam M., Walbert, Tobias, Rosenblum, Mark, Mikkelsen, Tom, Kalkanis, Steven, Tirapelli, Daniela P. C., Weisenberger, Daniel J., Carlotti, Jr, Carlos G., Rock, Jack, Castro, Ana Valeria, and Noushmehr, Houtan

Published
2023
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6. Predicting master transcription factors from pan-cancer expression data

Author

Reddy, Jessica, Fonseca, Marcos AS, Corona, Rosario I, Nameki, Robbin, Segato Dezem, Felipe, Klein, Isaac A, Chang, Heidi, Chaves-Moreira, Daniele, Afeyan, Lena K, Malta, Tathiane M, Lin, Xianzhi, Abbasi, Forough, Font-Tello, Alba, Sabedot, Thais, Cejas, Paloma, Rodríguez-Malavé, Norma, Seo, Ji-Heui, Lin, De-Chen, Matulonis, Ursula, Karlan, Beth Y, Gayther, Simon A, Pasaniuc, Bogdan, Gusev, Alexander, Noushmehr, Houtan, Long, Henry, Freedman, Matthew L, Drapkin, Ronny, Young, Richard A, Abraham, Brian J, and Lawrenson, Kate

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Rare Diseases, Genetics, Ovarian Cancer, Human Genome
Abstract

Critical developmental “master transcription factors” (MTFs) can be subverted during tumorigenesis to control oncogenic transcriptional programs. Current approaches to identifying MTFs rely on ChIP-seq data, which is unavailable for many cancers. We developed the CaCTS (Cancer Core Transcription factor Specificity) algorithm to prioritize candidate MTFs using pan-cancer RNA sequencing data. CaCTS identified candidate MTFs across 34 tumor types and 140 subtypes including predictions for cancer types/subtypes for which MTFs are unknown, including e.g. PAX8, SOX17, and MECOM as candidates in ovarian cancer (OvCa). In OvCa cells, consistent with known MTF properties, these factors are required for viability, lie proximal to superenhancers, co-occupy regulatory elements globally, co-bind loci encoding OvCa biomarkers, and are sensitive to pharmacologic inhibition of transcription. Our predictions of MTFs, especially for tumor types with limited understanding of transcriptional drivers, pave the way to therapeutic targeting of MTFs in a broad spectrum of cancers.

Published
2021

7. Advances in Central Nervous System Tumor Classification

Author

Malta, Tathiane M., Snyder, James, Noushmehr, Houtan, Castro, Ana Valeria, Crusio, Wim E., Series Editor, Dong, Haidong, Series Editor, Radeke, Heinfried H., Series Editor, Rezaei, Nima, Series Editor, Steinlein, Ortrud, Series Editor, Xiao, Junjie, Series Editor, Zadeh, Gelareh, editor, Goldbrunner, Roland, editor, Krischek, Boris, editor, and Nassiri, Farshad, editor

Published
2023
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8. Longitudinal molecular trajectories of diffuse glioma in adults

Author

Barthel, Floris P, Johnson, Kevin C, Varn, Frederick S, Moskalik, Anzhela D, Tanner, Georgette, Kocakavuk, Emre, Anderson, Kevin J, Abiola, Olajide, Aldape, Kenneth, Alfaro, Kristin D, Alpar, Donat, Amin, Samirkumar B, Ashley, David M, Bandopadhayay, Pratiti, Barnholtz-Sloan, Jill S, Beroukhim, Rameen, Bock, Christoph, Brastianos, Priscilla K, Brat, Daniel J, Brodbelt, Andrew R, Bruns, Alexander F, Bulsara, Ketan R, Chakrabarty, Aruna, Chakravarti, Arnab, Chuang, Jeffrey H, Claus, Elizabeth B, Cochran, Elizabeth J, Connelly, Jennifer, Costello, Joseph F, Finocchiaro, Gaetano, Fletcher, Michael N, French, Pim J, Gan, Hui K, Gilbert, Mark R, Gould, Peter V, Grimmer, Matthew R, Iavarone, Antonio, Ismail, Azzam, Jenkinson, Michael D, Khasraw, Mustafa, Kim, Hoon, Kouwenhoven, Mathilde CM, LaViolette, Peter S, Li, Meihong, Lichter, Peter, Ligon, Keith L, Lowman, Allison K, Malta, Tathiane M, Mazor, Tali, McDonald, Kerrie L, Molinaro, Annette M, Nam, Do-Hyun, Nayyar, Naema, Ng, Ho Keung, Ngan, Chew Yee, Niclou, Simone P, Niers, Johanna M, Noushmehr, Houtan, Noorbakhsh, Javad, Ormond, D Ryan, Park, Chul-Kee, Poisson, Laila M, Rabadan, Raul, Radlwimmer, Bernhard, Rao, Ganesh, Reifenberger, Guido, Sa, Jason K, Schuster, Michael, Shaw, Brian L, Short, Susan C, Smitt, Peter A Sillevis, Sloan, Andrew E, Smits, Marion, Suzuki, Hiromichi, Tabatabai, Ghazaleh, Van Meir, Erwin G, Watts, Colin, Weller, Michael, Wesseling, Pieter, Westerman, Bart A, Widhalm, Georg, Woehrer, Adelheid, Yung, WK Alfred, Zadeh, Gelareh, Huse, Jason T, De Groot, John F, Stead, Lucy F, and Verhaak, Roel GW

Subjects
Neurosciences, Brain Disorders, Cancer, Rare Diseases, Brain Cancer, Genetics, Adult, Chromosomes, Human, Pair 1, Chromosomes, Human, Pair 19, Disease Progression, Glioma, Humans, Isocitrate Dehydrogenase, Mutation, Polymorphism, Single Nucleotide, Recurrence, GLASS Consortium, General Science & Technology
Abstract

The evolutionary processes that drive universal therapeutic resistance in adult patients with diffuse glioma remain unclear1,2. Here we analysed temporally separated DNA-sequencing data and matched clinical annotation from 222 adult patients with glioma. By analysing mutations and copy numbers across the three major subtypes of diffuse glioma, we found that driver genes detected at the initial stage of disease were retained at recurrence, whereas there was little evidence of recurrence-specific gene alterations. Treatment with alkylating agents resulted in a hypermutator phenotype at different rates across the glioma subtypes, and hypermutation was not associated with differences in overall survival. Acquired aneuploidy was frequently detected in recurrent gliomas and was characterized by IDH mutation but without co-deletion of chromosome arms 1p/19q, and further converged with acquired alterations in the cell cycle and poor outcomes. The clonal architecture of each tumour remained similar over time, but the presence of subclonal selection was associated with decreased survival. Finally, there were no differences in the levels of immunoediting between initial and recurrent gliomas. Collectively, our results suggest that the strongest selective pressures occur during early glioma development and that current therapies shape this evolution in a largely stochastic manner.

Published
2019

9. Table S1 from The Epigenetic Evolution of Glioma Is Determined by the IDH1 Mutation Status and Treatment Regimen

Author

Malta, Tathiane M., primary, Sabedot, Thais S., primary, Morosini, Natalia S., primary, Datta, Indrani, primary, Garofano, Luciano, primary, Vallentgoed, Wies, primary, Varn, Frederick S., primary, Aldape, Kenneth, primary, D'Angelo, Fulvio, primary, Bakas, Spyridon, primary, Barnholtz-Sloan, Jill S., primary, Gan, Hui K., primary, Hasanain, Mohammad, primary, Hau, Ann-Christin, primary, Johnson, Kevin C., primary, Cazacu, Simona, primary, deCarvalho, Ana C., primary, Khasraw, Mustafa, primary, Kocakavuk, Emre, primary, Kouwenhoven, Mathilde C.M., primary, Migliozzi, Simona, primary, Niclou, Simone P., primary, Niers, Johanna M., primary, Ormond, D. Ryan, primary, Paek, Sun Ha, primary, Reifenberger, Guido, primary, Sillevis Smitt, Peter A., primary, Smits, Marion, primary, Stead, Lucy F., primary, van den Bent, Martin J., primary, Van Meir, Erwin G., primary, Walenkamp, Annemiek, primary, Weiss, Tobias, primary, Weller, Michael, primary, Westerman, Bart A., primary, Ylstra, Bauke, primary, Wesseling, Pieter, primary, Lasorella, Anna, primary, French, Pim J., primary, Poisson, Laila M., primary, Woehrer, Adelheid, primary, Lowman, Allison K, primary, deCarvalho, Ana C, primary, Castro, Ana Valeria, primary, Transou, Andrea, primary, Brodbelt, Andrew R, primary, Golebiewska, Anna, primary, Molinaro, Annette M, primary, Iavarone, Antonio, primary, Ismail, Azzam, primary, Westerman, Bart A, primary, Bock, Christoph, primary, Brat, Daniel J, primary, Van Meir, Erwin G, primary, Barthel, Floris P, primary, Varn, Frederick S, primary, Finocchiaro, Gaetano, primary, Rao, Ganesh, primary, Zadeh, Gelareh, primary, ngNg, Ho Keu, primary, Kim, Hoon, primary, Noushmehr, Houtan, primary, Miletic, Hrvoje, primary, Gan, Hui K, primary, Rock, Jack, primary, Snyder, James M, primary, Huse, Jason T, primary, Connelly, Jennifer M, primary, Barnholtz-Sloan, Jill S, primary, Niers, Johanna M, primary, deGroot, John F, primary, Akdemir, Kadir C, primary, Kannan, Kasthuri S, primary, Ligon, Keith L, primary, Bulsara, Ketan R, primary, Johnson, Kevin C, primary, Alfaro, Kristin D, primary, Poisson, Laila M, primary, Stead, Lucy F, primary, Nasrallah, MacLean P, primary, van den Bent, Martin J, primary, Kouwenhoven, Mathilde CM, primary, Gould, Peter V, primary, Smitt, Peter A Sillevis, primary, LaViolette, Peter S, primary, Tatman, Philip D, primary, French, Pim J, primary, Beroukhim, Rameen, primary, Verhaak, Roel G.W., primary, Niclou, Simone P, primary, Kalkanis, Steven, primary, Short, Susan C, primary, Ghazaleh, Tabatabai, primary, Malta, Tathiane M, primary, Sabedot, Thais S, primary, Walbert, Tobias, primary, Baid, Ujjwal, primary, and Yung, W. K. Alfred, primary

Published
2024
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10. Supp Figures from The Epigenetic Evolution of Glioma Is Determined by the IDH1 Mutation Status and Treatment Regimen

Author

Malta, Tathiane M., primary, Sabedot, Thais S., primary, Morosini, Natalia S., primary, Datta, Indrani, primary, Garofano, Luciano, primary, Vallentgoed, Wies, primary, Varn, Frederick S., primary, Aldape, Kenneth, primary, D'Angelo, Fulvio, primary, Bakas, Spyridon, primary, Barnholtz-Sloan, Jill S., primary, Gan, Hui K., primary, Hasanain, Mohammad, primary, Hau, Ann-Christin, primary, Johnson, Kevin C., primary, Cazacu, Simona, primary, deCarvalho, Ana C., primary, Khasraw, Mustafa, primary, Kocakavuk, Emre, primary, Kouwenhoven, Mathilde C.M., primary, Migliozzi, Simona, primary, Niclou, Simone P., primary, Niers, Johanna M., primary, Ormond, D. Ryan, primary, Paek, Sun Ha, primary, Reifenberger, Guido, primary, Sillevis Smitt, Peter A., primary, Smits, Marion, primary, Stead, Lucy F., primary, van den Bent, Martin J., primary, Van Meir, Erwin G., primary, Walenkamp, Annemiek, primary, Weiss, Tobias, primary, Weller, Michael, primary, Westerman, Bart A., primary, Ylstra, Bauke, primary, Wesseling, Pieter, primary, Lasorella, Anna, primary, French, Pim J., primary, Poisson, Laila M., primary, Woehrer, Adelheid, primary, Lowman, Allison K, primary, deCarvalho, Ana C, primary, Castro, Ana Valeria, primary, Transou, Andrea, primary, Brodbelt, Andrew R, primary, Golebiewska, Anna, primary, Molinaro, Annette M, primary, Iavarone, Antonio, primary, Ismail, Azzam, primary, Westerman, Bart A, primary, Bock, Christoph, primary, Brat, Daniel J, primary, Van Meir, Erwin G, primary, Barthel, Floris P, primary, Varn, Frederick S, primary, Finocchiaro, Gaetano, primary, Rao, Ganesh, primary, Zadeh, Gelareh, primary, ngNg, Ho Keu, primary, Kim, Hoon, primary, Noushmehr, Houtan, primary, Miletic, Hrvoje, primary, Gan, Hui K, primary, Rock, Jack, primary, Snyder, James M, primary, Huse, Jason T, primary, Connelly, Jennifer M, primary, Barnholtz-Sloan, Jill S, primary, Niers, Johanna M, primary, deGroot, John F, primary, Akdemir, Kadir C, primary, Kannan, Kasthuri S, primary, Ligon, Keith L, primary, Bulsara, Ketan R, primary, Johnson, Kevin C, primary, Alfaro, Kristin D, primary, Poisson, Laila M, primary, Stead, Lucy F, primary, Nasrallah, MacLean P, primary, van den Bent, Martin J, primary, Kouwenhoven, Mathilde CM, primary, Gould, Peter V, primary, Smitt, Peter A Sillevis, primary, LaViolette, Peter S, primary, Tatman, Philip D, primary, French, Pim J, primary, Beroukhim, Rameen, primary, Verhaak, Roel G.W., primary, Niclou, Simone P, primary, Kalkanis, Steven, primary, Short, Susan C, primary, Ghazaleh, Tabatabai, primary, Malta, Tathiane M, primary, Sabedot, Thais S, primary, Walbert, Tobias, primary, Baid, Ujjwal, primary, and Yung, W. K. Alfred, primary

Published
2024
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11. Supplemental Figures Legends from The Epigenetic Evolution of Glioma Is Determined by the IDH1 Mutation Status and Treatment Regimen

Author

Malta, Tathiane M., primary, Sabedot, Thais S., primary, Morosini, Natalia S., primary, Datta, Indrani, primary, Garofano, Luciano, primary, Vallentgoed, Wies, primary, Varn, Frederick S., primary, Aldape, Kenneth, primary, D'Angelo, Fulvio, primary, Bakas, Spyridon, primary, Barnholtz-Sloan, Jill S., primary, Gan, Hui K., primary, Hasanain, Mohammad, primary, Hau, Ann-Christin, primary, Johnson, Kevin C., primary, Cazacu, Simona, primary, deCarvalho, Ana C., primary, Khasraw, Mustafa, primary, Kocakavuk, Emre, primary, Kouwenhoven, Mathilde C.M., primary, Migliozzi, Simona, primary, Niclou, Simone P., primary, Niers, Johanna M., primary, Ormond, D. Ryan, primary, Paek, Sun Ha, primary, Reifenberger, Guido, primary, Sillevis Smitt, Peter A., primary, Smits, Marion, primary, Stead, Lucy F., primary, van den Bent, Martin J., primary, Van Meir, Erwin G., primary, Walenkamp, Annemiek, primary, Weiss, Tobias, primary, Weller, Michael, primary, Westerman, Bart A., primary, Ylstra, Bauke, primary, Wesseling, Pieter, primary, Lasorella, Anna, primary, French, Pim J., primary, Poisson, Laila M., primary, Woehrer, Adelheid, primary, Lowman, Allison K, primary, deCarvalho, Ana C, primary, Castro, Ana Valeria, primary, Transou, Andrea, primary, Brodbelt, Andrew R, primary, Golebiewska, Anna, primary, Molinaro, Annette M, primary, Iavarone, Antonio, primary, Ismail, Azzam, primary, Westerman, Bart A, primary, Bock, Christoph, primary, Brat, Daniel J, primary, Van Meir, Erwin G, primary, Barthel, Floris P, primary, Varn, Frederick S, primary, Finocchiaro, Gaetano, primary, Rao, Ganesh, primary, Zadeh, Gelareh, primary, ngNg, Ho Keu, primary, Kim, Hoon, primary, Noushmehr, Houtan, primary, Miletic, Hrvoje, primary, Gan, Hui K, primary, Rock, Jack, primary, Snyder, James M, primary, Huse, Jason T, primary, Connelly, Jennifer M, primary, Barnholtz-Sloan, Jill S, primary, Niers, Johanna M, primary, deGroot, John F, primary, Akdemir, Kadir C, primary, Kannan, Kasthuri S, primary, Ligon, Keith L, primary, Bulsara, Ketan R, primary, Johnson, Kevin C, primary, Alfaro, Kristin D, primary, Poisson, Laila M, primary, Stead, Lucy F, primary, Nasrallah, MacLean P, primary, van den Bent, Martin J, primary, Kouwenhoven, Mathilde CM, primary, Gould, Peter V, primary, Smitt, Peter A Sillevis, primary, LaViolette, Peter S, primary, Tatman, Philip D, primary, French, Pim J, primary, Beroukhim, Rameen, primary, Verhaak, Roel G.W., primary, Niclou, Simone P, primary, Kalkanis, Steven, primary, Short, Susan C, primary, Ghazaleh, Tabatabai, primary, Malta, Tathiane M, primary, Sabedot, Thais S, primary, Walbert, Tobias, primary, Baid, Ujjwal, primary, and Yung, W. K. Alfred, primary

Published
2024
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12. Data from The Epigenetic Evolution of Glioma Is Determined by the IDH1 Mutation Status and Treatment Regimen

Author

Malta, Tathiane M., primary, Sabedot, Thais S., primary, Morosini, Natalia S., primary, Datta, Indrani, primary, Garofano, Luciano, primary, Vallentgoed, Wies, primary, Varn, Frederick S., primary, Aldape, Kenneth, primary, D'Angelo, Fulvio, primary, Bakas, Spyridon, primary, Barnholtz-Sloan, Jill S., primary, Gan, Hui K., primary, Hasanain, Mohammad, primary, Hau, Ann-Christin, primary, Johnson, Kevin C., primary, Cazacu, Simona, primary, deCarvalho, Ana C., primary, Khasraw, Mustafa, primary, Kocakavuk, Emre, primary, Kouwenhoven, Mathilde C.M., primary, Migliozzi, Simona, primary, Niclou, Simone P., primary, Niers, Johanna M., primary, Ormond, D. Ryan, primary, Paek, Sun Ha, primary, Reifenberger, Guido, primary, Sillevis Smitt, Peter A., primary, Smits, Marion, primary, Stead, Lucy F., primary, van den Bent, Martin J., primary, Van Meir, Erwin G., primary, Walenkamp, Annemiek, primary, Weiss, Tobias, primary, Weller, Michael, primary, Westerman, Bart A., primary, Ylstra, Bauke, primary, Wesseling, Pieter, primary, Lasorella, Anna, primary, French, Pim J., primary, Poisson, Laila M., primary, Woehrer, Adelheid, primary, Lowman, Allison K, primary, deCarvalho, Ana C, primary, Castro, Ana Valeria, primary, Transou, Andrea, primary, Brodbelt, Andrew R, primary, Golebiewska, Anna, primary, Molinaro, Annette M, primary, Iavarone, Antonio, primary, Ismail, Azzam, primary, Westerman, Bart A, primary, Bock, Christoph, primary, Brat, Daniel J, primary, Van Meir, Erwin G, primary, Barthel, Floris P, primary, Varn, Frederick S, primary, Finocchiaro, Gaetano, primary, Rao, Ganesh, primary, Zadeh, Gelareh, primary, ngNg, Ho Keu, primary, Kim, Hoon, primary, Noushmehr, Houtan, primary, Miletic, Hrvoje, primary, Gan, Hui K, primary, Rock, Jack, primary, Snyder, James M, primary, Huse, Jason T, primary, Connelly, Jennifer M, primary, Barnholtz-Sloan, Jill S, primary, Niers, Johanna M, primary, deGroot, John F, primary, Akdemir, Kadir C, primary, Kannan, Kasthuri S, primary, Ligon, Keith L, primary, Bulsara, Ketan R, primary, Johnson, Kevin C, primary, Alfaro, Kristin D, primary, Poisson, Laila M, primary, Stead, Lucy F, primary, Nasrallah, MacLean P, primary, van den Bent, Martin J, primary, Kouwenhoven, Mathilde CM, primary, Gould, Peter V, primary, Smitt, Peter A Sillevis, primary, LaViolette, Peter S, primary, Tatman, Philip D, primary, French, Pim J, primary, Beroukhim, Rameen, primary, Verhaak, Roel G.W., primary, Niclou, Simone P, primary, Kalkanis, Steven, primary, Short, Susan C, primary, Ghazaleh, Tabatabai, primary, Malta, Tathiane M, primary, Sabedot, Thais S, primary, Walbert, Tobias, primary, Baid, Ujjwal, primary, and Yung, W. K. Alfred, primary

Published
2024
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13. Supplementary Appendix from The Epigenetic Evolution of Glioma Is Determined by the IDH1 Mutation Status and Treatment Regimen

Author

Malta, Tathiane M., primary, Sabedot, Thais S., primary, Morosini, Natalia S., primary, Datta, Indrani, primary, Garofano, Luciano, primary, Vallentgoed, Wies, primary, Varn, Frederick S., primary, Aldape, Kenneth, primary, D'Angelo, Fulvio, primary, Bakas, Spyridon, primary, Barnholtz-Sloan, Jill S., primary, Gan, Hui K., primary, Hasanain, Mohammad, primary, Hau, Ann-Christin, primary, Johnson, Kevin C., primary, Cazacu, Simona, primary, deCarvalho, Ana C., primary, Khasraw, Mustafa, primary, Kocakavuk, Emre, primary, Kouwenhoven, Mathilde C.M., primary, Migliozzi, Simona, primary, Niclou, Simone P., primary, Niers, Johanna M., primary, Ormond, D. Ryan, primary, Paek, Sun Ha, primary, Reifenberger, Guido, primary, Sillevis Smitt, Peter A., primary, Smits, Marion, primary, Stead, Lucy F., primary, van den Bent, Martin J., primary, Van Meir, Erwin G., primary, Walenkamp, Annemiek, primary, Weiss, Tobias, primary, Weller, Michael, primary, Westerman, Bart A., primary, Ylstra, Bauke, primary, Wesseling, Pieter, primary, Lasorella, Anna, primary, French, Pim J., primary, Poisson, Laila M., primary, Woehrer, Adelheid, primary, Lowman, Allison K, primary, deCarvalho, Ana C, primary, Castro, Ana Valeria, primary, Transou, Andrea, primary, Brodbelt, Andrew R, primary, Golebiewska, Anna, primary, Molinaro, Annette M, primary, Iavarone, Antonio, primary, Ismail, Azzam, primary, Westerman, Bart A, primary, Bock, Christoph, primary, Brat, Daniel J, primary, Van Meir, Erwin G, primary, Barthel, Floris P, primary, Varn, Frederick S, primary, Finocchiaro, Gaetano, primary, Rao, Ganesh, primary, Zadeh, Gelareh, primary, ngNg, Ho Keu, primary, Kim, Hoon, primary, Noushmehr, Houtan, primary, Miletic, Hrvoje, primary, Gan, Hui K, primary, Rock, Jack, primary, Snyder, James M, primary, Huse, Jason T, primary, Connelly, Jennifer M, primary, Barnholtz-Sloan, Jill S, primary, Niers, Johanna M, primary, deGroot, John F, primary, Akdemir, Kadir C, primary, Kannan, Kasthuri S, primary, Ligon, Keith L, primary, Bulsara, Ketan R, primary, Johnson, Kevin C, primary, Alfaro, Kristin D, primary, Poisson, Laila M, primary, Stead, Lucy F, primary, Nasrallah, MacLean P, primary, van den Bent, Martin J, primary, Kouwenhoven, Mathilde CM, primary, Gould, Peter V, primary, Smitt, Peter A Sillevis, primary, LaViolette, Peter S, primary, Tatman, Philip D, primary, French, Pim J, primary, Beroukhim, Rameen, primary, Verhaak, Roel G.W., primary, Niclou, Simone P, primary, Kalkanis, Steven, primary, Short, Susan C, primary, Ghazaleh, Tabatabai, primary, Malta, Tathiane M, primary, Sabedot, Thais S, primary, Walbert, Tobias, primary, Baid, Ujjwal, primary, and Yung, W. K. Alfred, primary

Published
2024
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14. The Immune Landscape of Cancer

Author

Thorsson, Vésteinn, Gibbs, David L, Brown, Scott D, Wolf, Denise, Bortone, Dante S, Yang, Tai-Hsien Ou, Porta-Pardo, Eduard, Gao, Galen F, Plaisier, Christopher L, Eddy, James A, Ziv, Elad, Culhane, Aedin C, Paull, Evan O, Sivakumar, IK Ashok, Gentles, Andrew J, Malhotra, Raunaq, Farshidfar, Farshad, Colaprico, Antonio, Parker, Joel S, Mose, Lisle E, Vo, Nam Sy, Liu, Jianfang, Liu, Yuexin, Rader, Janet, Dhankani, Varsha, Reynolds, Sheila M, Bowlby, Reanne, Califano, Andrea, Cherniack, Andrew D, Anastassiou, Dimitris, Bedognetti, Davide, Mokrab, Younes, Newman, Aaron M, Rao, Arvind, Chen, Ken, Krasnitz, Alexander, Hu, Hai, Malta, Tathiane M, Noushmehr, Houtan, Pedamallu, Chandra Sekhar, Bullman, Susan, Ojesina, Akinyemi I, Lamb, Andrew, Zhou, Wanding, Shen, Hui, Choueiri, Toni K, Weinstein, John N, Guinney, Justin, Saltz, Joel, Holt, Robert A, Rabkin, Charles S, Network, The Cancer Genome Atlas Research, Caesar-Johnson, Samantha J, Demchok, John A, Felau, Ina, Kasapi, Melpomeni, Ferguson, Martin L, Hutter, Carolyn M, Sofia, Heidi J, Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Zenklusen, Jean C, Zhang, Jiashan, Chudamani, Sudha, Liu, Jia, Lolla, Laxmi, Naresh, Rashi, Pihl, Todd, Sun, Qiang, Wan, Yunhu, Wu, Ye, Cho, Juok, DeFreitas, Timothy, Frazer, Scott, Gehlenborg, Nils, Getz, Gad, Heiman, David I, Kim, Jaegil, Lawrence, Michael S, Lin, Pei, Meier, Sam, Noble, Michael S, Saksena, Gordon, Voet, Doug, Zhang, Hailei, Bernard, Brady, Chambwe, Nyasha, Knijnenburg, Theo, Kramer, Roger, Leinonen, Kalle, Miller, Michael, Reynolds, Sheila, Shmulevich, Ilya, Thorsson, Vesteinn, Zhang, Wei, Akbani, Rehan, and Broom, Bradley M

Subjects
Biomedical and Clinical Sciences, Immunology, Cancer Genome Atlas Research Network
Abstract

(Immunity 48, 812–830.e1–e14; April 17, 2018) In the originally published version of this article, the authors neglected to include Younes Mokrab and Aaron M. Newman as co-authors and misspelled the names of authors Charles S. Rabkin and Ilya Shmulevich. The author names have been corrected here and online. In addition, the concluding sentence of the subsection “Immune Signature Compilation” in the Method Details in the original published article was deemed unclear because it did not specify differences among the gene set scoring methods. The concluding sentences now reads “Gene sets from Bindea et al., Senbabaoglu et al., and the MSigDB C7 collection were scored using single-sample gene set enrichment (ssGSEA) analysis (Barbie et al., 2009), as implemented in the GSVA R package (Hänzelmann et al., 2013). All other signatures were scored using methods found in the associated citations.”

Published
2019

16. The Immune Landscape of Cancer

Author

Thorsson, Vésteinn, Gibbs, David L, Brown, Scott D, Wolf, Denise, Bortone, Dante S, Ou Yang, Tai-Hsien, Porta-Pardo, Eduard, Gao, Galen F, Plaisier, Christopher L, Eddy, James A, Ziv, Elad, Culhane, Aedin C, Paull, Evan O, Sivakumar, IK Ashok, Gentles, Andrew J, Malhotra, Raunaq, Farshidfar, Farshad, Colaprico, Antonio, Parker, Joel S, Mose, Lisle E, Vo, Nam Sy, Liu, Jianfang, Liu, Yuexin, Rader, Janet, Dhankani, Varsha, Reynolds, Sheila M, Bowlby, Reanne, Califano, Andrea, Cherniack, Andrew D, Anastassiou, Dimitris, Bedognetti, Davide, Mokrab, Younes, Newman, Aaron M, Rao, Arvind, Chen, Ken, Krasnitz, Alexander, Hu, Hai, Malta, Tathiane M, Noushmehr, Houtan, Pedamallu, Chandra Sekhar, Bullman, Susan, Ojesina, Akinyemi I, Lamb, Andrew, Zhou, Wanding, Shen, Hui, Choueiri, Toni K, Weinstein, John N, Guinney, Justin, Saltz, Joel, Holt, Robert A, Rabkin, Charles S, Lazar, Alexander J, Serody, Jonathan S, Demicco, Elizabeth G, Disis, Mary L, Vincent, Benjamin G, Shmulevich, Ilya, Caesar-Johnson, Samantha J, Demchok, John A, Felau, Ina, Kasapi, Melpomeni, Ferguson, Martin L, Hutter, Carolyn M, Sofia, Heidi J, Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Zenklusen, Jean C, Zhang, Jiashan Julia, Chudamani, Sudha, Liu, Jia, Lolla, Laxmi, Naresh, Rashi, Pihl, Todd, Sun, Qiang, Wan, Yunhu, Wu, Ye, Cho, Juok, DeFreitas, Timothy, Frazer, Scott, Gehlenborg, Nils, Getz, Gad, Heiman, David I, Kim, Jaegil, Lawrence, Michael S, Lin, Pei, Meier, Sam, Noble, Michael S, Saksena, Gordon, Voet, Doug, Zhang, Hailei, Bernard, Brady, Chambwe, Nyasha, Knijnenburg, Theo, Kramer, Roger, Leinonen, Kalle, Miller, Michael, and Reynolds, Sheila

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Immunotherapy, Genetics, Human Genome, Cancer, Cancer Genomics, 2.1 Biological and endogenous factors, Inflammatory and immune system, Adolescent, Adult, Aged, Aged, 80 and over, Child, Female, Genomics, Humans, Interferon-gamma, Macrophages, Male, Middle Aged, Neoplasms, Prognosis, Th1-Th2 Balance, Transforming Growth Factor beta, Wound Healing, Young Adult, Cancer Genome Atlas Research Network, cancer genomics, immune subtypes, immuno-oncology, immunomodulatory, immunotherapy, integrative network analysis, tumor immunology, tumor microenvironment
Abstract

We performed an extensive immunogenomic analysis of more than 10,000 tumors comprising 33 diverse cancer types by utilizing data compiled by TCGA. Across cancer types, we identified six immune subtypes-wound healing, IFN-γ dominant, inflammatory, lymphocyte depleted, immunologically quiet, and TGF-β dominant-characterized by differences in macrophage or lymphocyte signatures, Th1:Th2 cell ratio, extent of intratumoral heterogeneity, aneuploidy, extent of neoantigen load, overall cell proliferation, expression of immunomodulatory genes, and prognosis. Specific driver mutations correlated with lower (CTNNB1, NRAS, or IDH1) or higher (BRAF, TP53, or CASP8) leukocyte levels across all cancers. Multiple control modalities of the intracellular and extracellular networks (transcription, microRNAs, copy number, and epigenetic processes) were involved in tumor-immune cell interactions, both across and within immune subtypes. Our immunogenomics pipeline to characterize these heterogeneous tumors and the resulting data are intended to serve as a resource for future targeted studies to further advance the field.

Published
2018

17. Machine Learning Identifies Stemness Features Associated with Oncogenic Dedifferentiation

Author

Malta, Tathiane M, Sokolov, Artem, Gentles, Andrew J, Burzykowski, Tomasz, Poisson, Laila, Weinstein, John N, Kamińska, Bożena, Huelsken, Joerg, Omberg, Larsson, Gevaert, Olivier, Colaprico, Antonio, Czerwińska, Patrycja, Mazurek, Sylwia, Mishra, Lopa, Heyn, Holger, Krasnitz, Alex, Godwin, Andrew K, Lazar, Alexander J, Network, The Cancer Genome Atlas Research, Caesar-Johnson, Samantha J, Demchok, John A, Felau, Ina, Kasapi, Melpomeni, Ferguson, Martin L, Hutter, Carolyn M, Sofia, Heidi J, Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Zenklusen, Jean C, Zhang, Jiashan, Chudamani, Sudha, Liu, Jia, Lolla, Laxmi, Naresh, Rashi, Pihl, Todd, Sun, Qiang, Wan, Yunhu, Wu, Ye, Cho, Juok, DeFreitas, Timothy, Frazer, Scott, Gehlenborg, Nils, Getz, Gad, Heiman, David I, Kim, Jaegil, Lawrence, Michael S, Lin, Pei, Meier, Sam, Noble, Michael S, Saksena, Gordon, Voet, Doug, Zhang, Hailei, Bernard, Brady, Chambwe, Nyasha, Dhankani, Varsha, Knijnenburg, Theo, Kramer, Roger, Leinonen, Kalle, Liu, Yuexin, Miller, Michael, Reynolds, Sheila, Shmulevich, Ilya, Thorsson, Vesteinn, Zhang, Wei, Akbani, Rehan, Broom, Bradley M, Hegde, Apurva M, Ju, Zhenlin, Kanchi, Rupa S, Korkut, Anil, Li, Jun, Liang, Han, Ling, Shiyun, Liu, Wenbin, Lu, Yiling, Mills, Gordon B, Ng, Kwok-Shing, Rao, Arvind, Ryan, Michael, Wang, Jing, Zhang, Jiexin, Abeshouse, Adam, Armenia, Joshua, Chakravarty, Debyani, Chatila, Walid K, de Bruijn, Ino, Gao, Jianjiong, Gross, Benjamin E, Heins, Zachary J, Kundra, Ritika, La, Konnor, Ladanyi, Marc, Luna, Augustin, Nissan, Moriah G, Ochoa, Angelica, Phillips, Sarah M, Reznik, Ed, and Sanchez-Vega, Francisco

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Cancer Genomics, Rare Diseases, Human Genome, Cancer, Stem Cell Research, Stem Cell Research - Nonembryonic - Human, Stem Cell Research - Nonembryonic - Non-Human, Stem Cell Research - Induced Pluripotent Stem Cell, Genetics, Machine Learning and Artificial Intelligence, Good Health and Well Being, Carcinogenesis, Cell Dedifferentiation, DNA Methylation, Databases, Genetic, Epigenesis, Genetic, Humans, Machine Learning, MicroRNAs, Neoplasm Metastasis, Neoplasms, Stem Cells, Transcriptome, Tumor Microenvironment, Cancer Genome Atlas Research Network, The Cancer Genome Atlas, cancer stem cells, dedifferentiation, epigenomic, genomic, machine learning, pan-cancer, stemness, Biological Sciences, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Cancer progression involves the gradual loss of a differentiated phenotype and acquisition of progenitor and stem-cell-like features. Here, we provide novel stemness indices for assessing the degree of oncogenic dedifferentiation. We used an innovative one-class logistic regression (OCLR) machine-learning algorithm to extract transcriptomic and epigenetic feature sets derived from non-transformed pluripotent stem cells and their differentiated progeny. Using OCLR, we were able to identify previously undiscovered biological mechanisms associated with the dedifferentiated oncogenic state. Analyses of the tumor microenvironment revealed unanticipated correlation of cancer stemness with immune checkpoint expression and infiltrating immune cells. We found that the dedifferentiated oncogenic phenotype was generally most prominent in metastatic tumors. Application of our stemness indices to single-cell data revealed patterns of intra-tumor molecular heterogeneity. Finally, the indices allowed for the identification of novel targets and possible targeted therapies aimed at tumor differentiation.

Published
2018

18. Cell-of-Origin Patterns Dominate the Molecular Classification of 10,000 Tumors from 33 Types of Cancer

Author

Hoadley, Katherine A, Yau, Christina, Hinoue, Toshinori, Wolf, Denise M, Lazar, Alexander J, Drill, Esther, Shen, Ronglai, Taylor, Alison M, Cherniack, Andrew D, Thorsson, Vésteinn, Akbani, Rehan, Bowlby, Reanne, Wong, Christopher K, Wiznerowicz, Maciej, Sanchez-Vega, Francisco, Robertson, A Gordon, Schneider, Barbara G, Lawrence, Michael S, Noushmehr, Houtan, Malta, Tathiane M, Network, The Cancer Genome Atlas, Caesar-Johnson, Samantha J, Demchok, John A, Felau, Ina, Kasapi, Melpomeni, Ferguson, Martin L, Hutter, Carolyn M, Sofia, Heidi J, Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Zenklusen, Jean C, Zhang, Jiashan, Chudamani, Sudha, Liu, Jia, Lolla, Laxmi, Naresh, Rashi, Pihl, Todd, Sun, Qiang, Wan, Yunhu, Wu, Ye, Cho, Juok, DeFreitas, Timothy, Frazer, Scott, Gehlenborg, Nils, Getz, Gad, Heiman, David I, Kim, Jaegil, Lin, Pei, Meier, Sam, Noble, Michael S, Saksena, Gordon, Voet, Doug, Zhang, Hailei, Bernard, Brady, Chambwe, Nyasha, Dhankani, Varsha, Knijnenburg, Theo, Kramer, Roger, Leinonen, Kalle, Liu, Yuexin, Miller, Michael, Reynolds, Sheila, Shmulevich, Ilya, Thorsson, Vesteinn, Zhang, Wei, Broom, Bradley M, Hegde, Apurva M, Ju, Zhenlin, Kanchi, Rupa S, Korkut, Anil, Li, Jun, Liang, Han, Ling, Shiyun, Liu, Wenbin, Lu, Yiling, Mills, Gordon B, Ng, Kwok-Shing, Rao, Arvind, Ryan, Michael, Wang, Jing, Weinstein, John N, Zhang, Jiexin, Abeshouse, Adam, Armenia, Joshua, Chakravarty, Debyani, Chatila, Walid K, de Bruijn, Ino, Gao, Jianjiong, Gross, Benjamin E, Heins, Zachary J, Kundra, Ritika, La, Konnor, Ladanyi, Marc, Luna, Augustin, Nissan, Moriah G, Ochoa, Angelica, and Phillips, Sarah M

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Genetics, Human Genome, Cancer Genomics, Networking and Information Technology R&D (NITRD), Biotechnology, Cancer, 2.1 Biological and endogenous factors, Aneuploidy, Chromosomes, Cluster Analysis, CpG Islands, DNA Methylation, Databases, Factual, Humans, MicroRNAs, Mutation, Neoplasm Proteins, Neoplasms, RNA, Messenger, Cancer Genome Atlas Network, TCGA, cancer, cell-of-origin, genome, methylome, organs, proteome, subtypes, tissues, transcriptome, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

We conducted comprehensive integrative molecular analyses of the complete set of tumors in The Cancer Genome Atlas (TCGA), consisting of approximately 10,000 specimens and representing 33 types of cancer. We performed molecular clustering using data on chromosome-arm-level aneuploidy, DNA hypermethylation, mRNA, and miRNA expression levels and reverse-phase protein arrays, of which all, except for aneuploidy, revealed clustering primarily organized by histology, tissue type, or anatomic origin. The influence of cell type was evident in DNA-methylation-based clustering, even after excluding sites with known preexisting tissue-type-specific methylation. Integrative clustering further emphasized the dominant role of cell-of-origin patterns. Molecular similarities among histologically or anatomically related cancer types provide a basis for focused pan-cancer analyses, such as pan-gastrointestinal, pan-gynecological, pan-kidney, and pan-squamous cancers, and those related by stemness features, which in turn may inform strategies for future therapeutic development.

Published
2018

19. Molecular landscape of IDH-mutant primary astrocytoma Grade IV/glioblastomas

Author

Wong, Queenie Hoi-Wing, Li, Kay Ka-Wai, Wang, Wei-Wei, Malta, Tathiane M., Noushmehr, Houtan, Grabovska, Yura, Jones, Chris, Chan, Aden Ka-Yin, Kwan, Johnny Sheung-Him, Huang, Queenie Jun-Qi, Wong, Gabriel Chun-Hei, Li, Wen-Cai, Liu, Xian-Zhi, Chen, Hong, Chan, Danny Tat-Ming, Mao, Ying, Zhang, Zhen-Yu, Shi, Zhi-Feng, and Ng, Ho-Keung

Published
2021
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20. The epigenetic evolution of glioma is determined by the IDH1 mutation status and treatment regimen

Author

Malta, Tathiane M; https://orcid.org/0000-0003-1129-5791, Sabedot, Thais S; https://orcid.org/0000-0002-7813-483X, Morosini, Natalia S; https://orcid.org/0000-0002-9294-9461, Datta, Indrani; https://orcid.org/0000-0001-7548-9881, Garofano, Luciano; https://orcid.org/0000-0001-8582-0865, Vallentgoed, Wies R; https://orcid.org/0000-0001-6373-7710, Varn, Frederick S; https://orcid.org/0000-0001-6307-016X, Aldape, Kenneth; https://orcid.org/0000-0001-5119-7550, D'Angelo, Fulvio; https://orcid.org/0000-0002-4940-4693, Bakas, Spyridon; https://orcid.org/0000-0001-8734-6482, Barnholtz-Sloan, Jill S; https://orcid.org/0000-0001-6190-9304, Gan, Hui K; https://orcid.org/0000-0001-7319-8546, Hasanain, Mohammad; https://orcid.org/0000-0001-5207-101X, Hau, Ann-Christin; https://orcid.org/0000-0002-4412-2355, Johnson, Kevin C; https://orcid.org/0000-0003-0016-5158, Cazacu, Simona; https://orcid.org/0000-0002-6085-4177, deCarvalho, Ana C; https://orcid.org/0000-0003-1183-4548, Khasraw, Mustafa; https://orcid.org/0000-0003-3249-9849, Kocakavuk, Emre; https://orcid.org/0000-0003-1920-0494, Kouwenhoven, Mathilde C M; https://orcid.org/0000-0001-5252-4365, Migliozzi, Simona; https://orcid.org/0000-0002-4870-8943, Niclou, Simone P; https://orcid.org/0000-0002-3417-9534, Niers, Johanna M; https://orcid.org/0000-0002-0366-8247, Ormond, D Ryan; https://orcid.org/0000-0001-7027-2915, Paek, Sun Ha; https://orcid.org/0000-0003-3007-8653, Reifenberger, Guido; https://orcid.org/0000-0002-1419-9837, Sillevis Smitt, Peter A; https://orcid.org/0000-0001-8044-6798, Smits, Marion; https://orcid.org/0000-0001-5563-2871, Weiss, Tobias; https://orcid.org/0000-0002-5533-9429, Weller, Michael; https://orcid.org/0000-0002-1748-174X, et al, Malta, Tathiane M; https://orcid.org/0000-0003-1129-5791, Sabedot, Thais S; https://orcid.org/0000-0002-7813-483X, Morosini, Natalia S; https://orcid.org/0000-0002-9294-9461, Datta, Indrani; https://orcid.org/0000-0001-7548-9881, Garofano, Luciano; https://orcid.org/0000-0001-8582-0865, Vallentgoed, Wies R; https://orcid.org/0000-0001-6373-7710, Varn, Frederick S; https://orcid.org/0000-0001-6307-016X, Aldape, Kenneth; https://orcid.org/0000-0001-5119-7550, D'Angelo, Fulvio; https://orcid.org/0000-0002-4940-4693, Bakas, Spyridon; https://orcid.org/0000-0001-8734-6482, Barnholtz-Sloan, Jill S; https://orcid.org/0000-0001-6190-9304, Gan, Hui K; https://orcid.org/0000-0001-7319-8546, Hasanain, Mohammad; https://orcid.org/0000-0001-5207-101X, Hau, Ann-Christin; https://orcid.org/0000-0002-4412-2355, Johnson, Kevin C; https://orcid.org/0000-0003-0016-5158, Cazacu, Simona; https://orcid.org/0000-0002-6085-4177, deCarvalho, Ana C; https://orcid.org/0000-0003-1183-4548, Khasraw, Mustafa; https://orcid.org/0000-0003-3249-9849, Kocakavuk, Emre; https://orcid.org/0000-0003-1920-0494, Kouwenhoven, Mathilde C M; https://orcid.org/0000-0001-5252-4365, Migliozzi, Simona; https://orcid.org/0000-0002-4870-8943, Niclou, Simone P; https://orcid.org/0000-0002-3417-9534, Niers, Johanna M; https://orcid.org/0000-0002-0366-8247, Ormond, D Ryan; https://orcid.org/0000-0001-7027-2915, Paek, Sun Ha; https://orcid.org/0000-0003-3007-8653, Reifenberger, Guido; https://orcid.org/0000-0002-1419-9837, Sillevis Smitt, Peter A; https://orcid.org/0000-0001-8044-6798, Smits, Marion; https://orcid.org/0000-0001-5563-2871, Weiss, Tobias; https://orcid.org/0000-0002-5533-9429, Weller, Michael; https://orcid.org/0000-0002-1748-174X, and et al

Abstract

Tumor adaptation or selection is thought to underlie therapy resistance in glioma. To investigate longitudinal epigenetic evolution of gliomas in response to therapeutic pressure, we performed an epigenomic analysis of 132 matched initial and recurrent tumors from patients with IDH-wildtype (IDHwt) and IDH-mutant (IDHmut) glioma. IDHwt gliomas showed a stable epigenome over time with relatively low levels of global methylation. The epigenome of IDHmut gliomas showed initial high levels of genome-wide DNA methylation that was progressively reduced to levels similar to those of IDHwt tumors. Integration of epigenomics, gene expression, and functional genomics identified HOXD13 as a master regulator of IDHmut astrocytoma evolution. Furthermore, relapse of IDHmut tumors was accompanied by histological progression that was associated with survival, as validated in an independent cohort. Finally, the initial cell composition of the tumor microenvironment varied between IDHwt and IDHmut tumors and changed differentially following treatment, suggesting increased neo-angiogenesis and T-cell infiltration upon treatment of IDHmut gliomas. This study provides one of the largest cohorts of paired longitudinal glioma samples with epigenomic, transcriptomic, and genomic profiling and suggests that treatment of IDHmut glioma is associated with epigenomic evolution towards an IDHwt-like phenotype.

Published
2024

21. The Epigenetic Evolution of Glioma Is Determined by the IDH1 Mutation Status and Treatment Regimen

Author

Malta, Tathiane M., Sabedot, Thais S., Morosini, Natalia S., Datta, Indrani, Garofano, Luciano, Vallentgoed, Wies, Varn, Frederick S., Aldape, Kenneth, D'Angelo, Fulvio, Bakas, Spyridon, Barnholtz-Sloan, Jill S., Gan, Hui K., Hasanain, Mohammad, Hau, Ann Christin, Johnson, Kevin C., Cazacu, Simona, deCarvalho, Ana C., Khasraw, Mustafa, Kocakavuk, Emre, Kouwenhoven, Mathilde C.M., Migliozzi, Simona, Niclou, Simone P., Niers, Johanna M., Ormond, D. Ryan, Paek, Sun Ha, Reifenberger, Guido, Smitt, Peter A.Sillevis, Smits, Marion, Stead, Lucy F., van den Bent, Martin J., Van Meir, Erwin G., Walenkamp, Annemiek, Weiss, Tobias, Weller, Michael, Westerman, Bart A., Ylstra, Bauke, Wesseling, Pieter, Lasorella, Anna, French, Pim J., Poisson, Laila M., Verhaak, Roel G.W., Iavarone, Antonio, Noushmehr, Houtan, Malta, Tathiane M., Sabedot, Thais S., Morosini, Natalia S., Datta, Indrani, Garofano, Luciano, Vallentgoed, Wies, Varn, Frederick S., Aldape, Kenneth, D'Angelo, Fulvio, Bakas, Spyridon, Barnholtz-Sloan, Jill S., Gan, Hui K., Hasanain, Mohammad, Hau, Ann Christin, Johnson, Kevin C., Cazacu, Simona, deCarvalho, Ana C., Khasraw, Mustafa, Kocakavuk, Emre, Kouwenhoven, Mathilde C.M., Migliozzi, Simona, Niclou, Simone P., Niers, Johanna M., Ormond, D. Ryan, Paek, Sun Ha, Reifenberger, Guido, Smitt, Peter A.Sillevis, Smits, Marion, Stead, Lucy F., van den Bent, Martin J., Van Meir, Erwin G., Walenkamp, Annemiek, Weiss, Tobias, Weller, Michael, Westerman, Bart A., Ylstra, Bauke, Wesseling, Pieter, Lasorella, Anna, French, Pim J., Poisson, Laila M., Verhaak, Roel G.W., Iavarone, Antonio, and Noushmehr, Houtan

Abstract

Tumor adaptation or selection is thought to underlie therapy resistance in glioma. To investigate longitudinal epigenetic evolution of gliomas in response to therapeutic pressure, we performed an epigenomic analysis of 132 matched initial and recurrent tumors from patients with IDH-wildtype (IDHwt) and IDH-mutant (IDHmut) glioma. IDHwt gliomas showed a stable epigenome over time with relatively low levels of global methylation. The epigenome of IDHmut gliomas showed initial high levels of genome-wide DNA methylation that was progressively reduced to levels similar to those of IDHwt tumors. Integration of epigenomics, gene expression, and functional genomics identified HOXD13 as a master regulator of IDHmut astrocytoma evolution. Furthermore, relapse of IDHmut tumors was accompanied by histologic progression that was associated with survival, as validated in an independent cohort. Finally, the initial cell composition of the tumor microenvironment varied between IDHwt and IDHmut tumors and changed differentially following treatment, suggesting increased neoangiogenesis and T-cell infiltration upon treatment of IDHmut gliomas. This study provides one of the largest cohorts of paired longitudinal glioma samples with epigenomic, transcriptomic, and genomic profiling and suggests that treatment of IDHmut glioma is associated with epigenomic evolution toward an IDHwt-like phenotype.

Published
2024

22. Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma

Author

Ceccarelli, Michele, Barthel, Floris P, Malta, Tathiane M, Sabedot, Thais S, Salama, Sofie R, Murray, Bradley A, Morozova, Olena, Newton, Yulia, Radenbaugh, Amie, Pagnotta, Stefano M, Anjum, Samreen, Wang, Jiguang, Manyam, Ganiraju, Zoppoli, Pietro, Ling, Shiyun, Rao, Arjun A, Grifford, Mia, Cherniack, Andrew D, Zhang, Hailei, Poisson, Laila, Carlotti, Carlos Gilberto, da Cunha Tirapelli, Daniela Pretti, Rao, Arvind, Mikkelsen, Tom, Lau, Ching C, Yung, WK Alfred, Rabadan, Raul, Huse, Jason, Brat, Daniel J, Lehman, Norman L, Barnholtz-Sloan, Jill S, Zheng, Siyuan, Hess, Kenneth, Rao, Ganesh, Meyerson, Matthew, Beroukhim, Rameen, Cooper, Lee, Akbani, Rehan, Wrensch, Margaret, Haussler, David, Aldape, Kenneth D, Laird, Peter W, Gutmann, David H, Network, TCGA Research, Arachchi, Harindra, Auman, J Todd, Balasundaram, Miruna, Balu, Saianand, Barnett, Gene, Baylin, Stephen, Bell, Sue, Benz, Christopher, Bir, Natalie, Black, Keith L, Bodenheimer, Tom, Boice, Lori, Bootwalla, Moiz S, Bowen, Jay, Bristow, Christopher A, Butterfield, Yaron SN, Chen, Qing-Rong, Chin, Lynda, Cho, Juok, Chuah, Eric, Chudamani, Sudha, Coetzee, Simon G, Cohen, Mark L, Colman, Howard, Couce, Marta, D’Angelo, Fulvio, Davidsen, Tanja, Davis, Amy, Demchok, John A, Devine, Karen, Ding, Li, Duell, Rebecca, Elder, J Bradley, Eschbacher, Jennifer M, Fehrenbach, Ashley, Ferguson, Martin, Frazer, Scott, Fuller, Gregory, Fulop, Jordonna, Gabriel, Stacey B, Garofano, Luciano, Gastier-Foster, Julie M, Gehlenborg, Nils, Gerken, Mark, Getz, Gad, Giannini, Caterina, Gibson, William J, Hadjipanayis, Angela, Hayes, D Neil, Heiman, David I, Hermes, Beth, Hilty, Joe, Hoadley, Katherine A, Hoyle, Alan P, and Huang, Mei

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Bioinformatics and Computational Biology, Genetics, Oncology and Carcinogenesis, Orphan Drug, Brain Cancer, Brain Disorders, Biotechnology, Human Genome, Rare Diseases, Neurosciences, Cancer, Adult, Brain Neoplasms, Cell Proliferation, Cluster Analysis, DNA Helicases, DNA Methylation, Epigenesis, Genetic, Glioma, Humans, Isocitrate Dehydrogenase, Middle Aged, Mutation, Nuclear Proteins, Promoter Regions, Genetic, Signal Transduction, Telomerase, Telomere, Transcriptome, X-linked Nuclear Protein, TCGA Research Network, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Therapy development for adult diffuse glioma is hindered by incomplete knowledge of somatic glioma driving alterations and suboptimal disease classification. We defined the complete set of genes associated with 1,122 diffuse grade II-III-IV gliomas from The Cancer Genome Atlas and used molecular profiles to improve disease classification, identify molecular correlations, and provide insights into the progression from low- to high-grade disease. Whole-genome sequencing data analysis determined that ATRX but not TERT promoter mutations are associated with increased telomere length. Recent advances in glioma classification based on IDH mutation and 1p/19q co-deletion status were recapitulated through analysis of DNA methylation profiles, which identified clinically relevant molecular subsets. A subtype of IDH mutant glioma was associated with DNA demethylation and poor outcome; a group of IDH-wild-type diffuse glioma showed molecular similarity to pilocytic astrocytoma and relatively favorable survival. Understanding of cohesive disease groups may aid improved clinical outcomes.

Published
2016

23. The epigenetic evolution of glioma is determined by the IDH1 mutation status and treatment regimen

Author

Malta, Tathiane M., primary, Sabedot, Thais S., additional, Morosini, Natalia S., additional, Datta, Indrani, additional, Garofano, Luciano, additional, Vallentgoed, Wies R., additional, Varn, Frederick S., additional, Aldape, Kenneth, additional, D'Angelo, Fulvio, additional, Bakas, Spyridon, additional, Barnholtz-Sloan, Jill S., additional, Gan, Hui K., additional, Hasanain, Mohammad, additional, Hau, Ann-Christin, additional, Johnson, Kevin C., additional, Cazacu, Simona, additional, deCarvalho, Ana C., additional, Khasraw, Mustafa, additional, Kocakavuk, Emre, additional, Kouwenhoven, Mathilde C.M., additional, Migliozzi, Simona, additional, Niclou, Simone P., additional, Niers, Johanna M., additional, Ormond, D. Ryan., additional, Paek, Sun Ha, additional, Reifenberger, Guido, additional, Sillevis Smitt, Peter A., additional, Smits, Marion, additional, Stead, Lucy F., additional, van den Bent, Martin J., additional, Van Meir, Erwin G., additional, Walenkamp, Annemiek, additional, Weiss, Tobias, additional, Weller, Michael, additional, Westerman, Bart A., additional, Ylstra, Bauke, additional, Wesseling, Pieter, additional, Lasorella, Anna, additional, French, Pim J., additional, Poisson, Laila M., additional, Consortium, The GLASS, additional, Verhaak, Roel G.W., additional, Iavarone, Antonio, additional, and Noushmehr, Houtan, additional

Published
2023
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24. Patient-derived organoids and orthotopic xenografts of primary and recurrent gliomas represent relevant patient avatars for precision oncology

Author

Golebiewska, Anna, Hau, Ann-Christin, Oudin, Anaïs, Stieber, Daniel, Yabo, Yahaya A., Baus, Virginie, Barthelemy, Vanessa, Klein, Eliane, Bougnaud, Sébastien, Keunen, Olivier, Wantz, May, Michelucci, Alessandro, Neirinckx, Virginie, Muller, Arnaud, Kaoma, Tony, Nazarov, Petr V., Azuaje, Francisco, De Falco, Alfonso, Flies, Ben, Richart, Lorraine, Poovathingal, Suresh, Arns, Thais, Grzyb, Kamil, Mock, Andreas, Herold-Mende, Christel, Steino, Anne, Brown, Dennis, May, Patrick, Miletic, Hrvoje, Malta, Tathiane M., Noushmehr, Houtan, Kwon, Yong-Jun, Jahn, Winnie, Klink, Barbara, Tanner, Georgette, Stead, Lucy F., Mittelbronn, Michel, Skupin, Alexander, Hertel, Frank, Bjerkvig, Rolf, and Niclou, Simone P.

Published
2020
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26. Data from Targeting the E3 Ubiquitin Ligase PJA1 Enhances Tumor-Suppressing TGFβ Signaling

Author

Chen, Jian, primary, Mitra, Abhisek, primary, Li, Shulin, primary, Song, Shumei, primary, Nguyen, Bao-Ngoc, primary, Chen, Jiun-Sheng, primary, Shin, Ji-Hyun, primary, Gough, Nancy R., primary, Lin, Paul, primary, Obias, Vincent, primary, He, Aiwu Ruth, primary, Yao, Zhixing, primary, Malta, Tathiane M., primary, Noushmehr, Houtan, primary, Latham, Patricia S., primary, Su, Xiaoping, primary, Rashid, Asif, primary, Mishra, Bibhuti, primary, Wu, Ray-Chang, primary, and Mishra, Lopa, primary

Published
2023
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27. Supplementary Figures and legends from Targeting the E3 Ubiquitin Ligase PJA1 Enhances Tumor-Suppressing TGFβ Signaling

Author

Chen, Jian, primary, Mitra, Abhisek, primary, Li, Shulin, primary, Song, Shumei, primary, Nguyen, Bao-Ngoc, primary, Chen, Jiun-Sheng, primary, Shin, Ji-Hyun, primary, Gough, Nancy R., primary, Lin, Paul, primary, Obias, Vincent, primary, He, Aiwu Ruth, primary, Yao, Zhixing, primary, Malta, Tathiane M., primary, Noushmehr, Houtan, primary, Latham, Patricia S., primary, Su, Xiaoping, primary, Rashid, Asif, primary, Mishra, Bibhuti, primary, Wu, Ray-Chang, primary, and Mishra, Lopa, primary

Published
2023
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28. Supplementary Table 2 from Targeting the E3 Ubiquitin Ligase PJA1 Enhances Tumor-Suppressing TGFβ Signaling

Author

Chen, Jian, primary, Mitra, Abhisek, primary, Li, Shulin, primary, Song, Shumei, primary, Nguyen, Bao-Ngoc, primary, Chen, Jiun-Sheng, primary, Shin, Ji-Hyun, primary, Gough, Nancy R., primary, Lin, Paul, primary, Obias, Vincent, primary, He, Aiwu Ruth, primary, Yao, Zhixing, primary, Malta, Tathiane M., primary, Noushmehr, Houtan, primary, Latham, Patricia S., primary, Su, Xiaoping, primary, Rashid, Asif, primary, Mishra, Bibhuti, primary, Wu, Ray-Chang, primary, and Mishra, Lopa, primary

Published
2023
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29. Supplementary Table 3 from Targeting the E3 Ubiquitin Ligase PJA1 Enhances Tumor-Suppressing TGFβ Signaling

Author

Chen, Jian, primary, Mitra, Abhisek, primary, Li, Shulin, primary, Song, Shumei, primary, Nguyen, Bao-Ngoc, primary, Chen, Jiun-Sheng, primary, Shin, Ji-Hyun, primary, Gough, Nancy R., primary, Lin, Paul, primary, Obias, Vincent, primary, He, Aiwu Ruth, primary, Yao, Zhixing, primary, Malta, Tathiane M., primary, Noushmehr, Houtan, primary, Latham, Patricia S., primary, Su, Xiaoping, primary, Rashid, Asif, primary, Mishra, Bibhuti, primary, Wu, Ray-Chang, primary, and Mishra, Lopa, primary

Published
2023
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30. Supplementary Materials and Methods-PJA1-Cancer research from Targeting the E3 Ubiquitin Ligase PJA1 Enhances Tumor-Suppressing TGFβ Signaling

Author

Chen, Jian, primary, Mitra, Abhisek, primary, Li, Shulin, primary, Song, Shumei, primary, Nguyen, Bao-Ngoc, primary, Chen, Jiun-Sheng, primary, Shin, Ji-Hyun, primary, Gough, Nancy R., primary, Lin, Paul, primary, Obias, Vincent, primary, He, Aiwu Ruth, primary, Yao, Zhixing, primary, Malta, Tathiane M., primary, Noushmehr, Houtan, primary, Latham, Patricia S., primary, Su, Xiaoping, primary, Rashid, Asif, primary, Mishra, Bibhuti, primary, Wu, Ray-Chang, primary, and Mishra, Lopa, primary

Published
2023
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31. Supplementary Table 4 from Targeting the E3 Ubiquitin Ligase PJA1 Enhances Tumor-Suppressing TGFβ Signaling

Author

Chen, Jian, primary, Mitra, Abhisek, primary, Li, Shulin, primary, Song, Shumei, primary, Nguyen, Bao-Ngoc, primary, Chen, Jiun-Sheng, primary, Shin, Ji-Hyun, primary, Gough, Nancy R., primary, Lin, Paul, primary, Obias, Vincent, primary, He, Aiwu Ruth, primary, Yao, Zhixing, primary, Malta, Tathiane M., primary, Noushmehr, Houtan, primary, Latham, Patricia S., primary, Su, Xiaoping, primary, Rashid, Asif, primary, Mishra, Bibhuti, primary, Wu, Ray-Chang, primary, and Mishra, Lopa, primary

Published
2023
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32. Supplementary Table 1 from Targeting the E3 Ubiquitin Ligase PJA1 Enhances Tumor-Suppressing TGFβ Signaling

Author

Chen, Jian, primary, Mitra, Abhisek, primary, Li, Shulin, primary, Song, Shumei, primary, Nguyen, Bao-Ngoc, primary, Chen, Jiun-Sheng, primary, Shin, Ji-Hyun, primary, Gough, Nancy R., primary, Lin, Paul, primary, Obias, Vincent, primary, He, Aiwu Ruth, primary, Yao, Zhixing, primary, Malta, Tathiane M., primary, Noushmehr, Houtan, primary, Latham, Patricia S., primary, Su, Xiaoping, primary, Rashid, Asif, primary, Mishra, Bibhuti, primary, Wu, Ray-Chang, primary, and Mishra, Lopa, primary

Published
2023
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34. Mast cell-T cell axis alters development of colitis-dependent and colitis-independent colorectal tumours: potential for therapeutically targeting via mast cell inhibition

Author

Sakita, Juliana Y, primary, Elias-Oliveira, Jefferson, additional, Carlos, Daniela, additional, de Souza Santos, Emerson, additional, Almeida, Luciana Yamamoto, additional, Malta, Tathiane M, additional, Brunaldi, Mariângela O, additional, Albuquerque, Sergio, additional, Araújo Silva, Cleide Lúcia, additional, Andrade, Marcus V, additional, Bonato, Vania L D, additional, Garcia, Sergio Britto, additional, Cunha, Fernando Queiroz, additional, Cebinelli, Guilherme Cesar Martelossi, additional, Martins, Ronaldo B, additional, Matthews, Jason, additional, Colli, Leandro, additional, Martin, Francis L, additional, Uyemura, Sergio A, additional, and Kannen, Vinicius, additional

Published
2022
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36. Molecular landscape of IDH‐wild type, pTERT‐wild type adult glioblastomas

Author

Liu, Emma Munan, primary, Shi, Zhi‐Feng, additional, Li, Kay Ka‐Wai, additional, Malta, Tathiane M., additional, Chung, Nellie Yuk‐Fei, additional, Chen, Hong, additional, Chan, Janice Yuen‐Tung, additional, Poon, Manix Fung‐Man, additional, Kwan, Johnny Sheung‐Him, additional, Chan, Danny Tat‐Ming, additional, Noushmehr, Houtan, additional, Mao, Ying, additional, and Ng, Ho‐Keung, additional

Published
2022
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37. Detection of tumor-specific DNA methylation markers in the blood of patients with pituitary neuroendocrine tumors

Author

Herrgott, Grayson A, primary, Asmaro, Karam P, additional, Wells, Michael, additional, Sabedot, Thais S, additional, Malta, Tathiane M, additional, Mosella, Maritza S, additional, Nelson, Kevin, additional, Scarpace, Lisa, additional, Barnholtz-Sloan, Jill S, additional, Sloan, Andrew E, additional, Selman, Warren R, additional, deCarvalho, Ana C, additional, Poisson, Laila M, additional, Mukherjee, Abir, additional, Robin, Adam M, additional, Lee, Ian Y, additional, Snyder, James, additional, Walbert, Tobias, additional, Rosenblum, Mark, additional, Mikkelsen, Tom, additional, Bhan, Arti, additional, Craig, John, additional, Kalkanis, Steven, additional, Rock, Jack, additional, Noushmehr, Houtan, additional, and Castro, Ana Valeria, additional

Published
2022
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38. A global metagenomic map of urban microbiomes and antimicrobial resistance

Author

Danko, David, primary, Bezdan, Daniela, additional, Afshin, Evan E., additional, Ahsanuddin, Sofia, additional, Bhattacharya, Chandrima, additional, Butler, Daniel J., additional, Chng, Kern Rei, additional, Donnellan, Daisy, additional, Hecht, Jochen, additional, Jackson, Katelyn, additional, Kuchin, Katerina, additional, Karasikov, Mikhail, additional, Lyons, Abigail, additional, Mak, Lauren, additional, Meleshko, Dmitry, additional, Mustafa, Harun, additional, Mutai, Beth, additional, Neches, Russell Y., additional, Ng, Amanda, additional, Nikolayeva, Olga, additional, Nikolayeva, Tatyana, additional, Png, Eileen, additional, Ryon, Krista A., additional, Sanchez, Jorge L., additional, Shaaban, Heba, additional, Sierra, Maria A., additional, Thomas, Dominique, additional, Young, Ben, additional, Abudayyeh, Omar O., additional, Alicea, Josue, additional, Bhattacharyya, Malay, additional, Blekhman, Ran, additional, Castro-Nallar, Eduardo, additional, Cañas, Ana M., additional, Chatziefthimiou, Aspassia D., additional, Crawford, Robert W., additional, De Filippis, Francesca, additional, Deng, Youping, additional, Desnues, Christelle, additional, Dias-Neto, Emmanuel, additional, Dybwad, Marius, additional, Elhaik, Eran, additional, Ercolini, Danilo, additional, Frolova, Alina, additional, Gankin, Dennis, additional, Gootenberg, Jonathan S., additional, Graf, Alexandra B., additional, Green, David C., additional, Hajirasouliha, Iman, additional, Hastings, Jaden J.A., additional, Hernandez, Mark, additional, Iraola, Gregorio, additional, Jang, Soojin, additional, Kahles, Andre, additional, Kelly, Frank J., additional, Knights, Kaymisha, additional, Kyrpides, Nikos C., additional, Łabaj, Paweł P., additional, Lee, Patrick K.H., additional, Leung, Marcus H.Y., additional, Ljungdahl, Per O., additional, Mason-Buck, Gabriella, additional, McGrath, Ken, additional, Meydan, Cem, additional, Mongodin, Emmanuel F., additional, Moraes, Milton Ozorio, additional, Nagarajan, Niranjan, additional, Nieto-Caballero, Marina, additional, Noushmehr, Houtan, additional, Oliveira, Manuela, additional, Ossowski, Stephan, additional, Osuolale, Olayinka O., additional, Özcan, Orhan, additional, Paez-Espino, David, additional, Rascovan, Nicolás, additional, Richard, Hugues, additional, Rätsch, Gunnar, additional, Schriml, Lynn M., additional, Semmler, Torsten, additional, Sezerman, Osman U., additional, Shi, Leming, additional, Shi, Tieliu, additional, Siam, Rania, additional, Song, Le Huu, additional, Suzuki, Haruo, additional, Court, Denise Syndercombe, additional, Tighe, Scott W., additional, Tong, Xinzhao, additional, Udekwu, Klas I., additional, Ugalde, Juan A., additional, Valentine, Brandon, additional, Vassilev, Dimitar I., additional, Vayndorf, Elena M., additional, Velavan, Thirumalaisamy P., additional, Wu, Jun, additional, Zambrano, María M., additional, Zhu, Jifeng, additional, Zhu, Sibo, additional, Mason, Christopher E., additional, Abdullah, Natasha, additional, Abraao, Marcos, additional, Adel, Ait-hamlat, additional, Afaq, Muhammad, additional, Al-Quaddoomi, Faisal S., additional, Alam, Ireen, additional, Albuquerque, Gabriela E., additional, Alexiev, Alex, additional, Ali, Kalyn, additional, Alvarado-Arnez, Lucia E., additional, Aly, Sarh, additional, Amachee, Jennifer, additional, Amorim, Maria G., additional, Ampadu, Majelia, additional, Amran, Muhammad Al-Fath, additional, An, Nala, additional, Andrew, Watson, additional, Andrianjakarivony, Harilanto, additional, Angelov, Michael, additional, Antelo, Verónica, additional, Aquino, Catharine, additional, Aranguren, Álvaro, additional, Araujo, Luiza F., additional, Vasquez Arevalo, Hitler Francois, additional, Arevalo, Jenny, additional, Arnan, Carme, additional, Alvarado Arnez, Lucia Elena, additional, Arredondo, Fernanda, additional, Arthur, Matthew, additional, Asenjo, Freddy, additional, Aung, Thomas Saw, additional, Auvinet, Juliette, additional, Aventin, Nuria, additional, Ayaz, Sadaf, additional, Baburyan, Silva, additional, Bakere, Abd-Manaaf, additional, Bakhl, Katrin, additional, Bartelli, Thais F., additional, Batdelger, Erdenetsetseg, additional, Baudon, François, additional, Becher, Kevin, additional, Bello, Carla, additional, Benchouaia, Médine, additional, Benisty, Hannah, additional, Benoiston, Anne-Sophie, additional, Benson, Joseph, additional, Benítez, Diego, additional, Bernardes, Juliana, additional, Bertrand, Denis, additional, Beurmann, Silvia, additional, Bitard-Feildel, Tristan, additional, Bittner, Lucie, additional, Black, Christina, additional, Blanc, Guillaume, additional, Blyther, Brittany, additional, Bode, Toni, additional, Boeri, Julia, additional, Boldgiv, Bazartseren, additional, Bolzli, Kevin, additional, Bordigoni, Alexia, additional, Borrelli, Ciro, additional, Bouchard, Sonia, additional, Bouly, Jean-Pierre, additional, Boyd, Alicia, additional, Branco, Gabriela P., additional, Breschi, Alessandra, additional, Brindefalk, Björn, additional, Brion, Christian, additional, Briones, Alan, additional, Buczansla, Paulina, additional, Burke, Catherine M., additional, Burrell, Aszia, additional, Butova, Alina, additional, Buttar, Irvind, additional, Bynoe, Jalia, additional, Bönigk, Sven, additional, Bøifot, Kari O., additional, Caballero, Hiram, additional, Cai, Xiao Wen, additional, Calderon, Dayana, additional, Cantillo, Angela, additional, Carbajo, Miguel, additional, Carbone, Alessandra, additional, Cardenas, Anais, additional, Carrillo, Katerine, additional, Casalot, Laurie, additional, Castro, Sofia, additional, Castro, Ana V., additional, Castro, Astred, additional, Castro, Ana Valeria B., additional, Cawthorne, Simone, additional, Cedillo, Jonathan, additional, Chaker, Salama, additional, Chalangal, Jasna, additional, Chan, Allison, additional, Chasapi, Anastasia I., additional, Chatziefthimiou, Starr, additional, Chaudhuri, Sreya Ray, additional, Chavan, Akash Keluth, additional, Chavez, Francisco, additional, Chem, Gregory, additional, Chen, Xiaoqing, additional, Chen, Michelle, additional, Chen, Jenn-Wei, additional, Chernomoretz, Ariel, additional, Chettouh, Allaeddine, additional, Cheung, Daisy, additional, Chicas, Diana, additional, Chiu, Shirley, additional, Choudhry, Hira, additional, Chrispin, Carl, additional, Ciaramella, Kianna, additional, Cifuentes, Erika, additional, Cohen, Jake, additional, Coil, David A., additional, Collin, Sylvie, additional, Conger, Colleen, additional, Conte, Romain, additional, Corsi, Flavia, additional, Cossio, Cecilia N., additional, Costa, Ana F., additional, Cuebas, Delisia, additional, D’Alessandro, Bruno, additional, Dahlhausen, Katherine E., additional, Darling, Aaron E., additional, Das, Pujita, additional, Davenport, Lucinda B., additional, David, Laurent, additional, Davidson, Natalie R., additional, Dayama, Gargi, additional, Delmas, Stéphane, additional, Deng, Chris K., additional, Dequeker, Chloé, additional, Desert, Alexandre, additional, Devi, Monika, additional, Dezem, Felipe S., additional, Dias, Clara N., additional, Donahoe, Timothy Ryan, additional, Dorado, Sonia, additional, Dorsey, LaShonda, additional, Dotsenko, Valeriia, additional, Du, Steven, additional, Dutan, Alexandra, additional, Eady, Naya, additional, Eisen, Jonathan A., additional, Elaskandrany, Miar, additional, Epping, Lennard, additional, Escalera-Antezana, Juan P., additional, Ettinger, Cassie L., additional, Faiz, Iqra, additional, Fan, Luice, additional, Farhat, Nadine, additional, Faure, Emile, additional, Fauzi, Fazlina, additional, Feigin, Charlie, additional, Felice, Skye, additional, Ferreira, Laís Pereira, additional, Figueroa, Gabriel, additional, Fleiss, Aubin, additional, Flores, Denisse, additional, Velasco Flores, Jhovana L., additional, Fonseca, Marcos A.S., additional, Foox, Jonathan, additional, Forero, Juan Carlos, additional, Francis, Aaishah, additional, French, Kelly, additional, Fresia, Pablo, additional, Friedman, Jacob, additional, Fuentes, Jaime J., additional, Galipon, Josephine, additional, Garcia, Mathilde, additional, Garcia, Laura, additional, García, Catalina, additional, Geiger, Annie, additional, Gerner, Samuel M., additional, Ghose, Sonia L., additional, Giang, Dao Phuong, additional, Giménez, Matías, additional, Giovannelli, Donato, additional, Githae, Dedan, additional, Gkotzis, Spyridon, additional, Godoy, Liliana, additional, Goldman, Samantha, additional, Gonnet, Gaston H., additional, Gonzalez, Juana, additional, Gonzalez, Andrea, additional, Gonzalez-Poblete, Camila, additional, Gray, Andrew, additional, Gregory, Tranette, additional, Greselle, Charlotte, additional, Guasco, Sophie, additional, Guerra, Juan, additional, Gurianova, Nika, additional, Haehr, Wolfgang, additional, Halary, Sebastien, additional, Hartkopf, Felix, additional, Hawkins-Zafarnia, Arya, additional, Hazrin-Chong, Nur Hazlin, additional, Helfrich, Eric, additional, Hell, Eva, additional, Henry, Tamera, additional, Hernandez, Samuel, additional, Hernandez, Pilar Lopez, additional, Hess-Homeier, David, additional, Hittle, Lauren E., additional, Hoan, Nghiem Xuan, additional, Holik, Aliaksei, additional, Homma, Chiaki, additional, Hoxie, Irene, additional, Huber, Michael, additional, Humphries, Elizabeth, additional, Hyland, Stephanie, additional, Hässig, Andrea, additional, Häusler, Roland, additional, Hüsser, Nathalie, additional, Petit, Robert A., additional, Iderzorig, Badamnyambuu, additional, Igarashi, Mizuki, additional, Iqbal, Shaikh B., additional, Ishikawa, Shino, additional, Ishizuka, Sakura, additional, Islam, Sharah, additional, Islam, Riham, additional, Ito, Kohei, additional, Ito, Sota, additional, Ito, Takayuki, additional, Ivankovic, Tomislav, additional, Iwashiro, Tomoki, additional, Jackson, Sarah, additional, Jacobs, JoAnn, additional, James, Marisano, additional, Jaubert, Marianne, additional, Jerier, Marie-Laure, additional, Jiminez, Esmeralda, additional, Jinfessa, Ayantu, additional, De Jong, Ymke, additional, Joo, Hyun Woo, additional, Jospin, Guilllaume, additional, Kajita, Takema, additional, Ahmad Kassim, Affifah Saadah, additional, Kato, Nao, additional, Kaur, Amrit, additional, Kaur, Inderjit, additional, de Souza Gomes Kehdy, Fernanda, additional, Khadka, Vedbar S., additional, Khan, Shaira, additional, Khavari, Mahshid, additional, Ki, Michelle, additional, Kim, Gina, additional, Kim, Hyung Jun, additional, Kim, Sangwan, additional, King, Ryan J., additional, KoLoMonaco, Giuseppe, additional, Koag, Ellen, additional, Kobko-Litskevitch, Nadezhda, additional, Korshevniuk, Maryna, additional, Kozhar, Michael, additional, Krebs, Jonas, additional, Kubota, Nanami, additional, Kuklin, Andrii, additional, Kumar, Sheelta S., additional, Kwong, Rachel, additional, Kwong, Lawrence, additional, Lafontaine, Ingrid, additional, Lago, Juliana, additional, Lai, Tsoi Ying, additional, Laine, Elodie, additional, Laiola, Manolo, additional, Lakhneko, Olha, additional, Lamba, Isha, additional, de Lamotte, Gerardo, additional, Lannes, Romain, additional, De Lazzari, Eleonora, additional, Leahy, Madeline, additional, Lee, Hyunjung, additional, Lee, Yunmi, additional, Lee, Lucy, additional, Lemaire, Vincent, additional, Leong, Emily, additional, Lewandowska, Dagmara, additional, Li, Chenhao, additional, Liang, Weijun, additional, Lin, Moses, additional, Lisboa, Priscilla, additional, Litskevitch, Anna, additional, Liu, Eric Minwei, additional, Liu, Tracy, additional, Livia, Mayra Arauco, additional, Lo, Yui Him, additional, Losim, Sonia, additional, Loubens, Manon, additional, Lu, Jennifer, additional, Lykhenko, Olexandr, additional, Lysakova, Simona, additional, Mahmoud, Salah, additional, Majid, Sara Abdul, additional, Makogon, Natalka, additional, Maldonado, Denisse, additional, Mallari, Krizzy, additional, Malta, Tathiane M., additional, Mamun, Maliha, additional, Manoir, Dimitri, additional, Marchandon, German, additional, Marciniak, Natalia, additional, Marinovic, Sonia, additional, Marques, Brunna, additional, Mathews, Nicole, additional, Matsuzaki, Yuri, additional, Matthys, Vincent, additional, May, Madelyn, additional, McComb, Elias, additional, Meagher, Annabelle, additional, Melamed, Adiell, additional, Menary, Wayne, additional, Mendez, Katterinne N., additional, Mendez, Ambar, additional, Mendy, Irène Mauricette, additional, Meng, Irene, additional, Menon, Ajay, additional, Menor, Mark, additional, Meoded, Roy, additional, Merino, Nancy, additional, Miah, Karishma, additional, Mignotte, Mathilde, additional, Miketic, Tanja, additional, Miranda, Wilson, additional, Mitsios, Athena, additional, Miura, Ryusei, additional, Miyake, Kunihiko, additional, Moccia, Maria D., additional, Mohan, Natasha, additional, Mohsin, Mohammed, additional, Moitra, Karobi, additional, Moldes, Mauricio, additional, Molina, Laura, additional, Molinet, Jennifer, additional, Molomjamts, Orgil-Erdene, additional, Moniruzzaman, Eftar, additional, Moon, Sookwon, additional, de Oliveira Moraes, Isabelle, additional, Moreno, Mario, additional, Mosella, Maritza S., additional, Moser, Josef W., additional, Mozsary, Christopher, additional, Muehlbauer, Amanda L., additional, Muner, Oasima, additional, Munia, Muntaha, additional, Munim, Naimah, additional, Muscat, Maureen, additional, Mustac, Tatjana, additional, Muñoz, Cristina, additional, Nadalin, Francesca, additional, Naeem, Areeg, additional, Nagy-Szakal, Dorottya, additional, Nakagawa, Mayuko, additional, Narce, Ashanti, additional, Nasu, Masaki, additional, Navarrete, Irene González, additional, Naveed, Hiba, additional, Nazario, Bryan, additional, Nedunuri, Narasimha Rao, additional, Neff, Thomas, additional, Nesimi, Aida, additional, Ng, Wan Chiew, additional, Ng, Synti, additional, Nguyen, Gloria, additional, Ngwa, Elsy, additional, Nicolas, Agier, additional, Nicolas, Pierre, additional, Nika, Abdollahi, additional, Noorzi, Hosna, additional, Nosrati, Avigdor, additional, Nunes, Diana N., additional, O’Brien, Kathryn, additional, O’Hara, Niamh B., additional, Oken, Gabriella, additional, Olawoyin, Rantimi A., additional, Oliete, Javier Quilez, additional, Olmeda, Kiara, additional, Oluwadare, Tolulope, additional, Oluwadare, Itunu A., additional, Ordioni, Nils, additional, Orpilla, Jenessa, additional, Orrego, Jacqueline, additional, Ortega, Melissa, additional, Osma, Princess, additional, Osuolale, Israel O., additional, Osuolale, Oluwatosin M., additional, Ota, Mitsuki, additional, Oteri, Francesco, additional, Oto, Yuya, additional, Ounit, Rachid, additional, Ouzounis, Christos A., additional, Pakrashi, Subhamitra, additional, Paras, Rachel, additional, Pardo-Este, Coral, additional, Park, Young-Ja, additional, Pastuszek, Paulina, additional, Patel, Suraj, additional, Pathmanathan, Jananan, additional, Patrignani, Andrea, additional, Perez, Manuel, additional, Peros, Ante, additional, Persaud, Sabrina, additional, Peters, Anisia, additional, Phillips, Adam, additional, Pineda, Lisbeth, additional, Pizzi, Melissa P., additional, Plaku, Alma, additional, Plaku, Alketa, additional, Pompa-Hogan, Brianna, additional, Portilla, María Gabriela, additional, Posada, Leonardo, additional, Priestman, Max, additional, Prithiviraj, Bharath, additional, Priya, Sambhawa, additional, Pugdeethosal, Phanthira, additional, Pugh, Catherine E., additional, Pulatov, Benjamin, additional, Pupiec, Angelika, additional, Pyrshev, Kyrylo, additional, Qing, Tao, additional, Rahiel, Saher, additional, Rahmatulloev, Savlatjon, additional, Rajendran, Kannan, additional, Ramcharan, Aneisa, additional, Ramirez-Rojas, Adan, additional, Rana, Shahryar, additional, Ratnanandan, Prashanthi, additional, Read, Timothy D., additional, Rehrauer, Hubert, additional, Richer, Renee, additional, Rivera, Alexis, additional, Rivera, Michelle, additional, Robertiello, Alessandro, additional, Robinson, Courtney, additional, Rodríguez, Paula, additional, Rojas, Nayra Aguilar, additional, Roldán, Paul, additional, Rosario, Anyelic, additional, Roth, Sandra, additional, Ruiz, Maria, additional, Boja Ruiz, Stephen Eduard, additional, Russell, Kaitlan, additional, Rybak, Mariia, additional, Sabedot, Thais S., additional, Sabina, Mahfuza, additional, Saito, Ikuto, additional, Saito, Yoshitaka, additional, Malca Salas, Gustavo Adolfo, additional, Salazar, Cecilia, additional, San, Kaung Myat, additional, Sanchez, Jorge, additional, Sanchir, Khaliun, additional, Sankar, Ryan, additional, de Souza Santos, Paulo Thiago, additional, Saravi, Zulena, additional, Sasaki, Kai, additional, Sato, Yuma, additional, Sato, Masaki, additional, Sato, Seisuke, additional, Sato, Ryo, additional, Sato, Kaisei, additional, Sayara, Nowshin, additional, Schaaf, Steffen, additional, Schacher, Oli, additional, Schinke, Anna-Lena M., additional, Schlapbach, Ralph, additional, Schori, Christian, additional, Schriml, Jason R., additional, Segato, Felipe, additional, Sepulveda, Felipe, additional, Serpa, Marianna S., additional, De Sessions, Paola F., additional, Severyn, Juan C., additional, Shakil, Maheen, additional, Shalaby, Sarah, additional, Shari, Aliyah, additional, Shim, Hyenah, additional, Shirahata, Hikaru, additional, Shiwa, Yuh, additional, Da Silva, Ophélie, additional, Silva, Jordana M., additional, Simon, Gwenola, additional, Singh, Shaleni K., additional, Sluzek, Kasia, additional, Smith, Rebecca, additional, So, Eunice, additional, Andreu Somavilla, Núria, additional, Sonohara, Yuya, additional, Rufino de Sousa, Nuno, additional, Souza, Camila, additional, Sperry, Jason, additional, Sprinsky, Nicolas, additional, Stark, Stefan G., additional, La Storia, Antonietta, additional, Suganuma, Kiyoshi, additional, Suliman, Hamood, additional, Sullivan, Jill, additional, Supie, Arif Asyraf Md, additional, Suzuki, Chisato, additional, Takagi, Sora, additional, Takahara, Fumie, additional, Takahashi, Naoya, additional, Takahashi, Kou, additional, Takeda, Tomoki, additional, Takenaka, Isabella K., additional, Tanaka, Soma, additional, Tang, Anyi, additional, Man Tang, Yuk, additional, Tarcitano, Emilio, additional, Tassinari, Andrea, additional, Taye, Mahdi, additional, Terrero, Alexis, additional, Thambiraja, Eunice, additional, Thiébaut, Antonin, additional, Thomas, Sade, additional, Thomas, Andrew M., additional, Togashi, Yuto, additional, Togashi, Takumi, additional, Tomaselli, Anna, additional, Tomita, Masaru, additional, Tomita, Itsuki, additional, Toth, Oliver, additional, Toussaint, Nora C., additional, Tran, Jennifer M., additional, Truong, Catalina, additional, Tsonev, Stefan I., additional, Tsuda, Kazutoshi, additional, Tsurumaki, Takafumi, additional, Tuz, Michelle, additional, Tymoshenko, Yelyzaveta, additional, Urgiles, Carmen, additional, Usui, Mariko, additional, Vacant, Sophie, additional, Vann, Laura E., additional, Velter, Fabienne, additional, Ventorino, Valeria, additional, Vera-Wolf, Patricia, additional, Vicedomini, Riccardo, additional, Suarez-Villamil, Michael A., additional, Vincent, Sierra, additional, Vivancos-Koopman, Renee, additional, Wan, Andrew, additional, Wang, Cindy, additional, Warashina, Tomoro, additional, Watanabe, Ayuki, additional, Weekes, Samuel, additional, Werner, Johannes, additional, Westfall, David, additional, Wieler, Lothar H., additional, Williams, Michelle, additional, Wolf, Silver A., additional, Wong, Brian, additional, Wong, Yan Ling, additional, Wong, Tyler, additional, Wright, Rasheena, additional, Wunderlin, Tina, additional, Yamanaka, Ryota, additional, Yang, Jingcheng, additional, Yano, Hirokazu, additional, Yeh, George C., additional, Yemets, Olena, additional, Yeskova, Tetiana, additional, Yoshikawa, Shusei, additional, Zafar, Laraib, additional, Zhang, Yang, additional, Zhang, Shu, additional, Zhang, Amy, additional, Zheng, Yuanting, additional, and Zubenko, Stas, additional

Published
2021
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39. DNA methylation-based signatures classify sporadic pituitary tumors according to clinicopathological features

Author

Mosella, Maritza S, primary, Sabedot, Thais S, additional, Silva, Tiago C, additional, Malta, Tathiane M, additional, Dezem, Felipe Segato, additional, Asmaro, Karam P, additional, Wells, Michael, additional, Mukherjee, Abir, additional, Poisson, Laila M, additional, Snyder, James, additional, deCarvalho, Ana C, additional, Walbert, Tobias, additional, Aho, Todd, additional, Kalkanis, Steven, additional, Elias, Paula C, additional, Antonini, Sonir R, additional, Rock, Jack, additional, Noushmehr, Houtan, additional, Castro, Margaret, additional, and Castro, Ana Valeria, additional

Published
2021
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40. A serum-based DNA methylation assay provides accurate detection of glioma

Author

Sabedot, Thais S, primary, Malta, Tathiane M, additional, Snyder, James, additional, Nelson, Kevin, additional, Wells, Michael, additional, deCarvalho, Ana C, additional, Mukherjee, Abir, additional, Chitale, Dhananjay A, additional, Mosella, Maritza S, additional, Sokolov, Artem, additional, Asmaro, Karam P, additional, Robin, Adam, additional, Rosenblum, Mark L, additional, Mikkelsen, Tom, additional, Rock, Jack, additional, Poisson, Laila M, additional, Lee, Ian, additional, Walbert, Tobias, additional, Kalkanis, Steven, additional, Iavarone, Antonio, additional, Castro, Ana Valeria, additional, and Noushmehr, Houtan, additional

Published
2021
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41. Patient-derived organoids and orthotopic xenografts of primary and recurrent gliomas represent relevant patient avatars for precision oncology.

Author

Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Luxembourg Centre for Systems Biomedicine (LCSB): Integrative Cell Signalling (Skupin Group) [research center], Departmanet of Life Sciences and Medicine [research center], Luxembourg Centre for Systems Biomedicine (LCSB): Neuropathology (Mittelbronn Group) [research center], Luxembourg Centre for Systems Biomedicine (LCSB): Interventional Neuroscience (Hertel Group) [research center], n°7.4615.18/Télévie-FNRS [sponsor], n°7.4632.17/Télévie-FNRS [sponsor], 766069/H2020 Marie Skłodowska-Curie Actions [sponsor], Pan-RTK/Fondation Cancer Luxembourg [sponsor], PEARL award - P16/BM/11192868/Fonds National de la Recherche Luxembourg [sponsor], C17/BM/11664971 FNR [sponsor], Golebiewska, Anna, Hau, Ann-Christin, Oudin, Anaïs, Stieber, Daniel, Yabo, Yahaya A., Baus, Virginie, Barthelemy, Vanessa, Klein, Eliane, Bougnaud, Sébastien, Keunen, Olivier, Wantz, May, Michelucci, Alessandro, Neirinckx, Virginie, Muller, Arnaud, Kaoma, Tony, Nazarov, Petr V., Azuaje, Francisco, De Falco, Alfonso, Flies, Ben, Richart, Lorraine, Poovathingal, Suresh, Arns, Thais, Grzyb, Kamil, Mock, Andreas, Herold-Mende, Christel, Steino, Anne, Brown, Dennis, May, Patrick, Miletic, Hrvoje, Malta, Tathiane M., Noushmehr, Houtan, Kwon, Yong-Jun, Jahn, Winnie, Klink, Barbara, Tanner, Georgette, Stead, Lucy F., Mittelbronn, Michel, Skupin, Alexander, Hertel, Frank, Bjerkvig, Rolf, Niclou, Simone, Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Luxembourg Centre for Systems Biomedicine (LCSB): Integrative Cell Signalling (Skupin Group) [research center], Departmanet of Life Sciences and Medicine [research center], Luxembourg Centre for Systems Biomedicine (LCSB): Neuropathology (Mittelbronn Group) [research center], Luxembourg Centre for Systems Biomedicine (LCSB): Interventional Neuroscience (Hertel Group) [research center], n°7.4615.18/Télévie-FNRS [sponsor], n°7.4632.17/Télévie-FNRS [sponsor], 766069/H2020 Marie Skłodowska-Curie Actions [sponsor], Pan-RTK/Fondation Cancer Luxembourg [sponsor], PEARL award - P16/BM/11192868/Fonds National de la Recherche Luxembourg [sponsor], C17/BM/11664971 FNR [sponsor], Golebiewska, Anna, Hau, Ann-Christin, Oudin, Anaïs, Stieber, Daniel, Yabo, Yahaya A., Baus, Virginie, Barthelemy, Vanessa, Klein, Eliane, Bougnaud, Sébastien, Keunen, Olivier, Wantz, May, Michelucci, Alessandro, Neirinckx, Virginie, Muller, Arnaud, Kaoma, Tony, Nazarov, Petr V., Azuaje, Francisco, De Falco, Alfonso, Flies, Ben, Richart, Lorraine, Poovathingal, Suresh, Arns, Thais, Grzyb, Kamil, Mock, Andreas, Herold-Mende, Christel, Steino, Anne, Brown, Dennis, May, Patrick, Miletic, Hrvoje, Malta, Tathiane M., Noushmehr, Houtan, Kwon, Yong-Jun, Jahn, Winnie, Klink, Barbara, Tanner, Georgette, Stead, Lucy F., Mittelbronn, Michel, Skupin, Alexander, Hertel, Frank, Bjerkvig, Rolf, and Niclou, Simone

Abstract

Patient-based cancer models are essential tools for studying tumor biology and for the assessment of drug responses in a translational context. We report the establishment a large cohort of unique organoids and patient-derived orthotopic xenografts (PDOX) of various glioma subtypes, including gliomas with mutations in IDH1, and paired longitudinal PDOX from primary and recurrent tumors of the same patient. We show that glioma PDOXs enable long-term propagation of patient tumors and represent clinically relevant patient avatars that retain histopathological, genetic, epigenetic, and transcriptomic features of parental tumors. We find no evidence of mouse-specific clonal evolution in glioma PDOXs. Our cohort captures individual molecular genotypes for precision medicine including mutations in IDH1, ATRX, TP53, MDM2/4, amplification of EGFR, PDGFRA, MET, CDK4/6, MDM2/4, and deletion of CDKN2A/B, PTCH, and PTEN. Matched longitudinal PDOX recapitulate the limited genetic evolution of gliomas observed in patients following treatment. At the histological level, we observe increased vascularization in the rat host as compared to mice. PDOX-derived standardized glioma organoids are amenable to high-throughput drug screens that can be validated in mice. We show clinically relevant responses to temozolomide (TMZ) and to targeted treatments, such as EGFR and CDK4/6 inhibitors in (epi)genetically defined subgroups, according to MGMT promoter and EGFR/CDK status, respectively. Dianhydrogalactitol (VAL-083), a promising bifunctional alkylating agent in the current clinical trial, displayed high therapeutic efficacy, and was able to overcome TMZ resistance in glioblastoma. Our work underscores the clinical relevance of glioma organoids and PDOX models for translational research and personalized treatment studies and represents a unique publicly available resource for precision oncology.

Published
2020

42. Primary and recurrent glioma patient-derived orthotopic xenografts (PDOX) represent relevant patient avatars for precision medicine

Author

Luxembourg Institute of Health - LIH [research center], Luxembourg Centre for Systems Biomedicine (LCSB): Integrative Cell Signalling (Skupin Group) [research center], Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Télévie-FNRS (Grants n°7.4632.17, 4615.18) [sponsor], Fondation Cancer Luxembourg (Pan-RTK Targeting) [sponsor], FNR; CORE Junior C17/BM/11664971/DEMICS [sponsor], GLIOTRAIN ITN funded by the European Union’s Horizon 2020 [sponsor], Marie Skłodowska-Curie grant agreement No 766069 [sponsor], FNR PEARL P16/BM/11192868 grant [sponsor], Golebiewska, Anna, Hau, Ann-Christin, Oudin, Anais, Stieber, Daniel, Yabo, Yahaya A., Baus, Virginie, Barthelemy, Vanessa, Klein, Eliane, Bougnaud, Sebastien, Keunen, Olivier, Wantz, May, Michelucci, Alessandro, Neirinckx, Virginie, Muller, Arnaud, Kaoma, Tony, Nazarov, Petr V., Azuaje, Francisco, De Falco, Alfonso, Flies, Ben, Richart, Lorraine, Poovathingal, Suresh, Arns, Thais, Grzyb, Kamil, Mock, Andreas, Herold-Mende, Christel, Steino, Anne, Brown, Dennis, May, Patrick, Miletic, Hrvoje, Malta, Tathiane M., Noushmehr, Houtan, Kwon, Yong-Jun, Jahn, Winnie, Klink, Barbara, Tanner, Georgette, Stead, Lucy F., Mittelbronn, Michel, Skupin, Alexander, Hertel, Frank, Bjerkvig, Rolf, Niclou, Simone, Luxembourg Institute of Health - LIH [research center], Luxembourg Centre for Systems Biomedicine (LCSB): Integrative Cell Signalling (Skupin Group) [research center], Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Télévie-FNRS (Grants n°7.4632.17, 4615.18) [sponsor], Fondation Cancer Luxembourg (Pan-RTK Targeting) [sponsor], FNR; CORE Junior C17/BM/11664971/DEMICS [sponsor], GLIOTRAIN ITN funded by the European Union’s Horizon 2020 [sponsor], Marie Skłodowska-Curie grant agreement No 766069 [sponsor], FNR PEARL P16/BM/11192868 grant [sponsor], Golebiewska, Anna, Hau, Ann-Christin, Oudin, Anais, Stieber, Daniel, Yabo, Yahaya A., Baus, Virginie, Barthelemy, Vanessa, Klein, Eliane, Bougnaud, Sebastien, Keunen, Olivier, Wantz, May, Michelucci, Alessandro, Neirinckx, Virginie, Muller, Arnaud, Kaoma, Tony, Nazarov, Petr V., Azuaje, Francisco, De Falco, Alfonso, Flies, Ben, Richart, Lorraine, Poovathingal, Suresh, Arns, Thais, Grzyb, Kamil, Mock, Andreas, Herold-Mende, Christel, Steino, Anne, Brown, Dennis, May, Patrick, Miletic, Hrvoje, Malta, Tathiane M., Noushmehr, Houtan, Kwon, Yong-Jun, Jahn, Winnie, Klink, Barbara, Tanner, Georgette, Stead, Lucy F., Mittelbronn, Michel, Skupin, Alexander, Hertel, Frank, Bjerkvig, Rolf, and Niclou, Simone

Abstract

Patient-derived cancer models are essential tools for studying tumor biology and preclinical interventions. Here, we show that glioma patient-derived orthotopic xenografts (PDOXs) enable long-term propagation of patient tumors and represent clinically relevant patient avatars. We created a large collection of PDOXs from primary and recurrent gliomas with and without mutations in IDH1, which retained histopathological, genetic, epigenetic and transcriptomic features of patient tumors with no mouse-specific clonal evolution. Longitudinal PDOX models recapitulate the limited genetic evolution of gliomas observed in patient tumors following treatment. PDOX-derived standardized tumor organoid cultures enabled assessment of drug responses, which were validated in mice. PDOXs showed clinically relevant responses to Temozolomide and to targeted treatments such as EGFR and CDK4/6 inhibitors in (epi)genetically defined groups, according to MGMT promoter and EGFR/CDK status respectively. Dianhydrogalactitol, a bifunctional alkylating agent, showed promising potential against glioblastoma. Our study underlines the clinical relevance of glioma PDOX models for translational research and personalized treatment studies.

Published
2020

45. Detection of Circulating Tumor-specific DNA Methylation Markers in the Blood of Patients with Pituitary Tumors

Author

Wells, Michael, primary, Asmaro, Karam P., additional, Sabedot, Thais S., additional, Malta, Tathiane M., additional, Mosella, Maritza S., additional, Nelson, Kevin, additional, Snyder, James, additional, deCarvalho, Ana, additional, Mukherjee, Abir, additional, Chitale, Dhananjay, additional, Robin, Adam, additional, Rosenblum, Mark, additional, Mikkelsen, Thomas, additional, Poisson, Laila M., additional, Lee, Ian Y., additional, Walbert, Tobias, additional, Bhan, Arti, additional, Kalkanis, Steven, additional, Rock, Jack, additional, Noushmehr, Houtan, additional, and Castro, Ana Valeria, additional

Published
2020
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46. Targeting the E3 Ubiquitin Ligase PJA1 Enhances Tumor-Suppressing TGFβ Signaling

Author

Chen, Jian, primary, Mitra, Abhisek, additional, Li, Shulin, additional, Song, Shumei, additional, Nguyen, Bao-Ngoc, additional, Chen, Jiun-Sheng, additional, Shin, Ji-Hyun, additional, Gough, Nancy R., additional, Lin, Paul, additional, Obias, Vincent, additional, He, Aiwu Ruth, additional, Yao, Zhixing, additional, Malta, Tathiane M., additional, Noushmehr, Houtan, additional, Latham, Patricia S., additional, Su, Xiaoping, additional, Rashid, Asif, additional, Mishra, Bibhuti, additional, Wu, Ray-Chang, additional, and Mishra, Lopa, additional

Published
2020
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47. DNA Methylation-based Signatures Classify Sporadic Pituitary Tumors According to Clinicopathological Features

Author

Mosella, Maritza S., primary, Sabedot, Thais S., additional, Silva, Tiago C., additional, Malta, Tathiane M., additional, Segato, Felipe D., additional, Asmaro, Karam P., additional, Wells, Michael, additional, Mukherjee, Abir, additional, Poisson, Laila M., additional, Snyder, James, additional, deCarvalho, Ana C., additional, Walbert T, Tobias, additional, Aho, Todd, additional, Kalkanis, Steven, additional, Elias, Paula C., additional, Antonini, Sonir R., additional, Rock, Jack, additional, Noushmehr, Houtan, additional, Castro, Margaret, additional, and Castro, Ana Valeria, additional

Published
2020
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48. Primary and recurrent glioma patient-derived orthotopic xenografts (PDOX) represent relevant patient avatars for precision medicine

Author

Golebiewska, Anna, primary, Hau, Ann-Christin, additional, Oudin, Anaïs, additional, Stieber, Daniel, additional, Yabo, Yahaya A., additional, Baus, Virginie, additional, Barthelemy, Vanessa, additional, Klein, Eliane, additional, Bougnaud, Sébastien, additional, Keunen, Olivier, additional, Wantz, May, additional, Michelucci, Alessandro, additional, Neirinckx, Virginie, additional, Muller, Arnaud, additional, Kaoma, Tony, additional, Nazarov, Petr V., additional, Azuaje, Francisco, additional, De Falco, Alfonso, additional, Flies, Ben, additional, Richart, Lorraine, additional, Poovathingal, Suresh, additional, Arns, Thais, additional, Grzyb, Kamil, additional, Mock, Andreas, additional, Herold-Mende, Christel, additional, Steino, Anne, additional, Brown, Dennis, additional, May, Patrick, additional, Miletic, Hrvoje, additional, Malta, Tathiane M., additional, Noushmehr, Houtan, additional, Kwon, Yong-Jun, additional, Jahn, Winnie, additional, Klink, Barbara, additional, Tanner, Georgette, additional, Stead, Lucy F., additional, Mittelbronn, Michel, additional, Skupin, Alexander, additional, Hertel, Frank, additional, Bjerkvig, Rolf, additional, and Niclou, Simone P., additional

Published
2020
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49. Mutated CEACAMs Disrupt Transforming Growth Factor Beta Signaling and Alter the Intestinal Microbiome to Promote Colorectal Carcinogenesis

Author

Gu, Shoujun, primary, Zaidi, Sobia, additional, Hassan, Md Imtaiyaz, additional, Mohammad, Taj, additional, Malta, Tathiane M., additional, Noushmehr, Houtan, additional, Nguyen, Bryan, additional, Crandall, Keith A., additional, Srivastav, Jigisha, additional, Obias, Vincent, additional, Lin, Paul, additional, Nguyen, Bao-Ngoc, additional, Yao, Michael, additional, Yao, Ren, additional, King, Charles Hadley, additional, Mazumder, Raja, additional, Mishra, Bibhuti, additional, Rao, Shuyun, additional, and Mishra, Lopa, additional

Published
2020
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50. Predicting master transcription factors from pan-cancer expression data

Author

Reddy, Jessica, primary, Fonseca, Marcos A. S., additional, Corona, Rosario I, additional, Nameki, Robbin, additional, Segato Dezem, Felipe, additional, Klein, Isaac A., additional, Chang, Heidi, additional, Chaves-Moreira, Daniele, additional, Afeyan, Lena, additional, Malta, Tathiane M, additional, Lin, Xianzhi, additional, Abbasi, Forough, additional, Font-Tello, Alba, additional, Sabedot, Thais, additional, Cejas, Paloma, additional, Rodríguez-Malavé, Norma, additional, Seo, Ji-Heui, additional, Lin, De-Chen, additional, Matulonis, Ursula, additional, Karlan, Beth Y, additional, Gayther, Simon A, additional, Gusev, Alexander, additional, Noushmehr, Houtan, additional, Long, Henry, additional, Freedman, Matthew L., additional, Drapkin, Ronny, additional, Abraham, Brian J, additional, Young, Richard A., additional, and Lawrenson, Kate, additional

Published
2019
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