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1,122 results on '"Mora, Jaume"'

2. Integrated genomic analysis reveals aberrations in WNT signaling in germ cell tumors of childhood and adolescence

Author

Xu, Lin, Pierce, Joshua L, Sanchez, Angelica, Chen, Kenneth S, Shukla, Abhay A, Fustino, Nicholas J, Stuart, Sarai H, Bagrodia, Aditya, Xiao, Xue, Guo, Lei, Krailo, Mark D, Shaikh, Furqan, Billmire, Deborah F, Pashankar, Farzana, Bestrashniy, Jessica, Oosterhuis, J Wolter, Gillis, Ad JM, Xie, Yang, Teot, Lisa, Mora, Jaume, Poynter, Jenny N, Rakheja, Dinesh, Looijenga, Leendert HJ, Draper, Bruce W, Frazier, A Lindsay, and Amatruda, James F

Subjects
Cancer, Genetics, Pediatric, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Male, Child, Infant, Female, Young Adult, Humans, Adolescent, Infant, Newborn, Child, Preschool, Adult, Wnt Signaling Pathway, Neoplasms, Germ Cell and Embryonal, Teratoma, Testicular Neoplasms, Genomics
Abstract

Germ cell tumors (GCTs) are neoplasms of the testis, ovary and extragonadal sites that occur in infants, children, adolescents and adults. Post-pubertal (type II) malignant GCTs may present as seminoma, non-seminoma or mixed histologies. In contrast, pre-pubertal (type I) GCTs are limited to (benign) teratoma and (malignant) yolk sac tumor (YST). Epidemiologic and molecular data have shown that pre- and post-pubertal GCTs arise by distinct mechanisms. Dedicated studies of the genomic landscape of type I and II GCT in children and adolescents are lacking. Here we present an integrated genomic analysis of extracranial GCTs across the age spectrum from 0-24 years. Activation of the WNT pathway by somatic mutation, copy-number alteration, and differential promoter methylation is a prominent feature of GCTs in children, adolescents and young adults, and is associated with poor clinical outcomes. Significantly, we find that small molecule WNT inhibitors can suppress GCT cells both in vitro and in vivo. These results highlight the importance of WNT pathway signaling in GCTs across all ages and provide a foundation for future efforts to develop targeted therapies for these cancers.

Published
2023

3. Failure of human rhombic lip differentiation underlies medulloblastoma formation

Author

Hendrikse, Liam D, Haldipur, Parthiv, Saulnier, Olivier, Millman, Jake, Sjoboen, Alexandria H, Erickson, Anders W, Ong, Winnie, Gordon, Victor, Coudière-Morrison, Ludivine, Mercier, Audrey L, Shokouhian, Mohammad, Suárez, Raúl A, Ly, Michelle, Borlase, Stephanie, Scott, David S, Vladoiu, Maria C, Farooq, Hamza, Sirbu, Olga, Nakashima, Takuma, Nambu, Shohei, Funakoshi, Yusuke, Bahcheli, Alec, Diaz-Mejia, J Javier, Golser, Joseph, Bach, Kathleen, Phuong-Bao, Tram, Skowron, Patryk, Wang, Evan Y, Kumar, Sachin A, Balin, Polina, Visvanathan, Abhirami, Lee, John JY, Ayoub, Ramy, Chen, Xin, Chen, Xiaodi, Mungall, Karen L, Luu, Betty, Bérubé, Pierre, Wang, Yu C, Pfister, Stefan M, Kim, Seung-Ki, Delattre, Olivier, Bourdeaut, Franck, Doz, François, Masliah-Planchon, Julien, Grajkowska, Wieslawa A, Loukides, James, Dirks, Peter, Fèvre-Montange, Michelle, Jouvet, Anne, French, Pim J, Kros, Johan M, Zitterbart, Karel, Bailey, Swneke D, Eberhart, Charles G, Rao, Amulya AN, Giannini, Caterina, Olson, James M, Garami, Miklós, Hauser, Peter, Phillips, Joanna J, Ra, Young S, de Torres, Carmen, Mora, Jaume, Li, Kay KW, Ng, Ho-Keung, Poon, Wai S, Pollack, Ian F, López-Aguilar, Enrique, Gillespie, G Yancey, Van Meter, Timothy E, Shofuda, Tomoko, Vibhakar, Rajeev, Thompson, Reid C, Cooper, Michael K, Rubin, Joshua B, Kumabe, Toshihiro, Jung, Shin, Lach, Boleslaw, Iolascon, Achille, Ferrucci, Veronica, de Antonellis, Pasqualino, Zollo, Massimo, Cinalli, Giuseppe, Robinson, Shenandoah, Stearns, Duncan S, Van Meir, Erwin G, Porrati, Paola, Finocchiaro, Gaetano, Massimino, Maura, Carlotti, Carlos G, Faria, Claudia C, Roussel, Martine F, Boop, Frederick, Chan, Jennifer A, Aldinger, Kimberly A, Razavi, Ferechte, Silvestri, Evelina, McLendon, Roger E, and Thompson, Eric M

Subjects
Stem Cell Research, Brain Disorders, Neurosciences, Rare Diseases, Stem Cell Research - Nonembryonic - Non-Human, Aetiology, 1.1 Normal biological development and functioning, Underpinning research, 2.1 Biological and endogenous factors, Cell Differentiation, Cell Lineage, Cerebellar Neoplasms, Cerebellum, Core Binding Factor alpha Subunits, Hedgehog Proteins, Histone Demethylases, Humans, Ki-67 Antigen, Medulloblastoma, Metencephalon, Muscle Proteins, Mutation, Otx Transcription Factors, Repressor Proteins, T-Box Domain Proteins, Transcription Factors, General Science & Technology
Abstract

Medulloblastoma (MB) comprises a group of heterogeneous paediatric embryonal neoplasms of the hindbrain with strong links to early development of the hindbrain1-4. Mutations that activate Sonic hedgehog signalling lead to Sonic hedgehog MB in the upper rhombic lip (RL) granule cell lineage5-8. By contrast, mutations that activate WNT signalling lead to WNT MB in the lower RL9,10. However, little is known about the more commonly occurring group 4 (G4) MB, which is thought to arise in the unipolar brush cell lineage3,4. Here we demonstrate that somatic mutations that cause G4 MB converge on the core binding factor alpha (CBFA) complex and mutually exclusive alterations that affect CBFA2T2, CBFA2T3, PRDM6, UTX and OTX2. CBFA2T2 is expressed early in the progenitor cells of the cerebellar RL subventricular zone in Homo sapiens, and G4 MB transcriptionally resembles these progenitors but are stalled in developmental time. Knockdown of OTX2 in model systems relieves this differentiation blockade, which allows MB cells to spontaneously proceed along normal developmental differentiation trajectories. The specific nature of the split human RL, which is destined to generate most of the neurons in the human brain, and its high level of susceptible EOMES+KI67+ unipolar brush cell progenitor cells probably predisposes our species to the development of G4 MB.

Published
2022

4. Subgroup and subtype-specific outcomes in adult medulloblastoma.

Author

Coltin, Hallie, Sundaresan, Lakshmikirupa, Smith, Kyle, Skowron, Patryk, Massimi, Luca, Eberhart, Charles, Schreck, Karisa, Gupta, Nalin, Weiss, William, Tirapelli, Daniela, Carlotti, Carlos, Li, Kay, Ryzhova, Marina, Golanov, Andrey, Zheludkova, Olga, Absalyamova, Oksana, Okonechnikov, Konstantin, Stichel, Damian, von Deimling, Andreas, Giannini, Caterina, Raskin, Scott, Van Meir, Erwin, Chan, Jennifer, Fults, Daniel, Chambless, Lola, Kim, Seung-Ki, Vasiljevic, Alexandre, Faure-Conter, Cecile, Vibhakar, Rajeev, Jung, Shin, Leary, Sarah, Mora, Jaume, McLendon, Roger, Pollack, Ian, Hauser, Peter, Grajkowska, Wieslawa, Rubin, Joshua, van Veelen, Marie-Lise, French, Pim, Kros, Johan, Liau, Linda, Pfister, Stefan, Kool, Marcel, Kijima, Noriyuki, Taylor, Michael, Packer, Roger, Northcott, Paul, Korshunov, Andrey, and Ramaswamy, Vijay

Subjects
Adult, DNA methylation profiling, Medulloblastoma, Molecular groups, Risk stratification, Adolescent, Adult, Biomarkers, Tumor, Cerebellar Neoplasms, Cohort Studies, Female, Humans, Male, Medulloblastoma, Progression-Free Survival, Risk Factors, Young Adult
Abstract

Medulloblastoma, a common pediatric malignant central nervous system tumour, represent a small proportion of brain tumours in adults. Previously it has been shown that in adults, Sonic Hedgehog (SHH)-activated tumours predominate, with Wingless-type (WNT) and Group 4 being less common, but molecular risk stratification remains a challenge. We performed an integrated analysis consisting of genome-wide methylation profiling, copy number profiling, somatic nucleotide variants and correlation of clinical variables across a cohort of 191 adult medulloblastoma cases identified through the Medulloblastoma Advanced Genomics International Consortium. We identified 30 WNT, 112 SHH, 6 Group 3, and 41 Group 4 tumours. Patients with SHH tumours were significantly older at diagnosis compared to other subgroups (p

Published
2021

5. The transcriptional landscape of Shh medulloblastoma.

Author

Skowron, Patryk, Farooq, Hamza, Cavalli, Florence MG, Morrissy, A Sorana, Ly, Michelle, Hendrikse, Liam D, Wang, Evan Y, Djambazian, Haig, Zhu, Helen, Mungall, Karen L, Trinh, Quang M, Zheng, Tina, Dai, Shizhong, Stucklin, Ana S Guerreiro, Vladoiu, Maria C, Fong, Vernon, Holgado, Borja L, Nor, Carolina, Wu, Xiaochong, Abd-Rabbo, Diala, Bérubé, Pierre, Wang, Yu Chang, Luu, Betty, Suarez, Raul A, Rastan, Avesta, Gillmor, Aaron H, Lee, John JY, Zhang, Xiao Yun, Daniels, Craig, Dirks, Peter, Malkin, David, Bouffet, Eric, Tabori, Uri, Loukides, James, Doz, François P, Bourdeaut, Franck, Delattre, Olivier O, Masliah-Planchon, Julien, Ayrault, Olivier, Kim, Seung-Ki, Meyronet, David, Grajkowska, Wieslawa A, Carlotti, Carlos G, de Torres, Carmen, Mora, Jaume, Eberhart, Charles G, Van Meir, Erwin G, Kumabe, Toshihiro, French, Pim J, Kros, Johan M, Jabado, Nada, Lach, Boleslaw, Pollack, Ian F, Hamilton, Ronald L, Rao, Amulya A Nageswara, Giannini, Caterina, Olson, James M, Bognár, László, Klekner, Almos, Zitterbart, Karel, Phillips, Joanna J, Thompson, Reid C, Cooper, Michael K, Rubin, Joshua B, Liau, Linda M, Garami, Miklós, Hauser, Peter, Li, Kay Ka Wai, Ng, Ho-Keung, Poon, Wai Sang, Yancey Gillespie, G, Chan, Jennifer A, Jung, Shin, McLendon, Roger E, Thompson, Eric M, Zagzag, David, Vibhakar, Rajeev, Ra, Young Shin, Garre, Maria Luisa, Schüller, Ulrich, Shofuda, Tomoko, Faria, Claudia C, López-Aguilar, Enrique, Zadeh, Gelareh, Hui, Chi-Chung, Ramaswamy, Vijay, Bailey, Swneke D, Jones, Steven J, Mungall, Andrew J, Moore, Richard A, Calarco, John A, Stein, Lincoln D, Bader, Gary D, Reimand, Jüri, Ragoussis, Jiannis, Weiss, William A, Marra, Marco A, Suzuki, Hiromichi, and Taylor, Michael D

Subjects
Humans, Medulloblastoma, Cerebellar Neoplasms, Signal Transduction, Gene Expression Regulation, Neoplastic, Adolescent, Adult, Middle Aged, Child, Child, Preschool, Infant, Female, Male, Hedgehog Proteins, Gene Regulatory Networks, Genetic Variation, Young Adult, Transcriptome, Pediatric Research Initiative, Brain Cancer, Pediatric, Rare Diseases, Genetics, Pediatric Cancer, Clinical Research, Brain Disorders, Neurosciences, Biotechnology, Human Genome, Cancer, 2.1 Biological and endogenous factors
Abstract

Sonic hedgehog medulloblastoma encompasses a clinically and molecularly diverse group of cancers of the developing central nervous system. Here, we use unbiased sequencing of the transcriptome across a large cohort of 250 tumors to reveal differences among molecular subtypes of the disease, and demonstrate the previously unappreciated importance of non-coding RNA transcripts. We identify alterations within the cAMP dependent pathway (GNAS, PRKAR1A) which converge on GLI2 activity and show that 18% of tumors have a genetic event that directly targets the abundance and/or stability of MYCN. Furthermore, we discover an extensive network of fusions in focally amplified regions encompassing GLI2, and several loss-of-function fusions in tumor suppressor genes PTCH1, SUFU and NCOR1. Molecular convergence on a subset of genes by nucleotide variants, copy number aberrations, and gene fusions highlight the key roles of specific pathways in the pathogenesis of Sonic hedgehog medulloblastoma and open up opportunities for therapeutic intervention.

Published
2021

6. EpiGe: A machine-learning strategy for rapid classification of medulloblastoma using PCR-based methyl-genotyping

Author

Gómez-González, Soledad, Llano, Joshua, Garcia, Marta, Garrido-Garcia, Alicia, Suñol, Mariona, Lemos, Isadora, Perez-Jaume, Sara, Salvador, Noelia, Gene-Olaciregui, Nagore, Galán, Raquel Arnau, Santa-María, Vicente, Perez-Somarriba, Marta, Castañeda, Alicia, Hinojosa, José, Winter, Ursula, Moreira, Francisco Barbosa, Lubieniecki, Fabiana, Vazquez, Valeria, Mora, Jaume, Cruz, Ofelia, La Madrid, Andrés Morales, Perera, Alexandre, and Lavarino, Cinzia

Published
2023
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7. Impact of liver tumour burden, alkaline phosphatase elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate: an analysis of the NETTER-1 study

Author

Strosberg, Jonathan, Kunz, Pamela L, Hendifar, Andrew, Yao, James, Bushnell, David, Kulke, Matthew H, Baum, Richard P, Caplin, Martyn, Ruszniewski, Philippe, Delpassand, Ebrahim, Hobday, Timothy, Verslype, Chris, Benson, Al, Srirajaskanthan, Rajaventhan, Pavel, Marianne, Mora, Jaume, Berlin, Jordan, Grande, Enrique, Reed, Nicholas, Seregni, Ettore, Paganelli, Giovanni, Severi, Stefano, Morse, Michael, Metz, David C, Ansquer, Catherine, Courbon, Frédéric, Al-Nahhas, Adil, Baudin, Eric, Giammarile, Francesco, Taïeb, David, Mittra, Erik, Wolin, Edward, O’Dorisio, Thomas M, Lebtahi, Rachida, Deroose, Christophe M, Grana, Chiara M, Bodei, Lisa, Öberg, Kjell, Polack, Berna Degirmenci, He, Beilei, Mariani, Maurizio F, Gericke, Germo, Santoro, Paola, Erion, Jack L, Ravasi, Laura, and Krenning, Eric

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Digestive Diseases, Clinical Research, Clinical Trials and Supportive Activities, Cancer, Alkaline Phosphatase, Humans, Liver Neoplasms, Neuroendocrine Tumors, Octreotide, Organometallic Compounds, Treatment Outcome, NETTER-1 study group, 177Lu-Dotatate, Liver tumour burden, NETTER-1, Neuroendocrine tumour, Other Physical Sciences, Clinical Sciences, Nuclear Medicine & Medical Imaging, Clinical sciences
Abstract

PurposeTo assess the impact of baseline liver tumour burden, alkaline phosphatase (ALP) elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate.MethodsIn the phase 3 NETTER-1 trial, patients with advanced, progressive midgut neuroendocrine tumours (NET) were randomised to 177Lu-Dotatate (every 8 weeks, four cycles) plus octreotide long-acting release (LAR) or to octreotide LAR 60 mg. Primary endpoint was progression-free survival (PFS). Analyses of PFS by baseline factors, including liver tumour burden, ALP elevation, and target lesion size, were performed using Kaplan-Meier estimates; hazard ratios (HRs) with corresponding 95% CIs were estimated using Cox regression.ResultsSignificantly prolonged median PFS occurred with 177Lu-Dotatate versus octreotide LAR 60 mg in patients with low ( 50%) liver tumour burden (HR 0.187, 0.216, 0.145), and normal or elevated ALP (HR 0.153, 0.177), and in the presence or absence of a large target lesion (diameter > 30 mm; HR, 0.213, 0.063). Within the 177Lu-Dotatate arm, no significant difference in PFS was observed amongst patients with low/moderate/high liver tumour burden (P = 0.7225) or with normal/elevated baseline ALP (P = 0.3532), but absence of a large target lesion was associated with improved PFS (P = 0.0222). Grade 3 and 4 liver function abnormalities were rare and did not appear to be associated with high baseline liver tumour burden.Conclusions177Lu-Dotatate demonstrated significant prolongation in PFS versus high-dose octreotide LAR in patients with advanced, progressive midgut NET, regardless of baseline liver tumour burden, elevated ALP, or the presence of a large target lesion. Clinicaltrials.gov : NCT01578239, EudraCT: 2011-005049-11.

Published
2020

8. Pattern of Relapse and Treatment Response in WNT-Activated Medulloblastoma

Author

Nobre, Liana, Zapotocky, Michal, Khan, Sara, Fukuoka, Kohei, Fonseca, Adriana, McKeown, Tara, Sumerauer, David, Vicha, Ales, Grajkowska, Wieslawa A, Trubicka, Joanna, Li, Kay Ka Wai, Ng, Ho-Keung, Massimi, Luca, Lee, Ji Yeoun, Kim, Seung-Ki, Zelcer, Shayna, Vasiljevic, Alexandre, Faure-Conter, Cécile, Hauser, Peter, Lach, Boleslaw, van Veelen-Vincent, Marie-Lise, French, Pim J, Van Meir, Erwin G, Weiss, William A, Gupta, Nalin, Pollack, Ian F, Hamilton, Ronald L, Rao, Amulya A Nageswara, Giannini, Caterina, Rubin, Joshua B, Moore, Andrew S, Chambless, Lola B, Vibhakar, Rajeev, Ra, Young Shin, Massimino, Maura, McLendon, Roger E, Wheeler, Helen, Zollo, Massimo, Ferruci, Veronica, Kumabe, Toshihiro, Faria, Claudia C, Sterba, Jaroslav, Jung, Shin, López-Aguilar, Enrique, Mora, Jaume, Carlotti, Carlos G, Olson, James M, Leary, Sarah, Cain, Jason, Krskova, Lenka, Zamecnik, Josef, Hawkins, Cynthia E, Tabori, Uri, Huang, Annie, Bartels, Ute, Northcott, Paul A, Taylor, Michael D, Yip, Stephen, Hansford, Jordan R, Bouffet, Eric, and Ramaswamy, Vijay

Subjects
Cancer, Clinical Research, Evaluation of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Adolescent, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor, Cerebellar Neoplasms, Child, Cyclophosphamide, Female, Humans, Ifosfamide, Male, Medulloblastoma, Middle Aged, Neoplasm Recurrence, Local, Progression-Free Survival, medulloblastoma, WNT, genomics, cyclophosphamide, chemotherapy, prognosis, survival
Abstract

Over the past decade, wingless-activated (WNT) medulloblastoma has been identified as a candidate for therapy de-escalation based on excellent survival; however, a paucity of relapses has precluded additional analyses of markers of relapse. To address this gap in knowledge, an international cohort of 93 molecularly confirmed WNT MB was assembled, where 5-year progression-free survival is 0.84 (95%, 0.763-0.925) with 15 relapsed individuals identified. Maintenance chemotherapy is identified as a strong predictor of relapse, with individuals receiving high doses of cyclophosphamide or ifosphamide having only one very late molecularly confirmed relapse (p = 0.032). The anatomical location of recurrence is metastatic in 12 of 15 relapses, with 8 of 12 metastatic relapses in the lateral ventricles. Maintenance chemotherapy, specifically cumulative cyclophosphamide doses, is a significant predictor of relapse across WNT MB. Future efforts to de-escalate therapy need to carefully consider not only the radiation dose but also the chemotherapy regimen and the propensity for metastatic relapses.

Published
2020

10. Desensitizing the autonomic nervous system to mitigate anti-GD2 monoclonal antibody side effects

Author

Mora, Jaume, primary, Climent, Alejandra, additional, Roldán, Mònica, additional, Flores, Marta Cecilia, additional, Varo, Amalia, additional, Perez-Jaume, Sara, additional, Jou, Cristina, additional, Celma, Mónica S., additional, Lazaro, Juan José, additional, Cheung, Irene, additional, Castañeda, Alicia, additional, Gorostegui, Maite, additional, Rodriguez, Eva, additional, Chamorro, Saray, additional, Muñoz, Juan Pablo, additional, and Cheung, Nai-Kong, additional

Published
2024
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11. #2668 New treatments, new challenges: nephrotoxicity associated to naxitamab in patients with high-risk neuroblastoma

Author

Sancho, Pedro Arango, primary, Rodríguez, Ana Cristina Aguilar, additional, Espinoza, Yarima López, additional, Marín, Emma Fortes, additional, Pérez, Juan Pablo Muñoz, additional, Obanos, Maite Gorostegui, additional, Baños, Yolanda Calzada, additional, Báez, Víctor Alfonso López, additional, Moreno, Marta Jiménez, additional, Sampera, Elena Codina, additional, Aris, Álvaro Madrid, additional, and Mora, Jaume, additional

Published
2024
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13. Selective histone methyltransferase G9a inhibition reduces metastatic development of Ewing sarcoma through the epigenetic regulation of NEU1

Author

García-Domínguez, Daniel J., Hajji, Nabil, López-Alemany, Roser, Sánchez-Molina, Sara, Figuerola-Bou, Elisabet, Morón Civanto, Francisco J., Rello-Varona, Santiago, Andrés-León, Eduardo, Benito, Adrián, Keun, Hector C., Mora, Jaume, Tirado, Óscar M., de Álava, Enrique, and Hontecillas-Prieto, Lourdes

Published
2022
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14. The Global Retinoblastoma Outcome Study: a prospective, cluster-based analysis of 4064 patients from 149 countries

Author

Fabian, Ido Didi, Abdallah, Elhassan, Abdullahi, Shehu U, Abdulqader, Rula A, Abdulrahaman, Aminatu A, Abouelnaga, Sherif, Ademola-Popoola, Dupe S, Adio, Adedayo, Afifi, Mahmoud A, Afshar, Armin R, Aggarwal, Priyanka, Aghaji, Ada E, Ahmad, Alia, Akib, Marliyanti NR, Akinsete, Adeseye, Al Harby, Lamis, Al Mesfer, Saleh, Al Ani, Mouroge H, Alarcón Portabella, Silvia, Al-Badri, Safaa AF, Alcasabas, Ana Patricia A, Al-Dahmash, Saad A, Alejos, Amanda, Alemany-Rubio, Ernesto, Alfa Bio, Amadou I, Alfonso Carreras, Yvania, Al-Haddad, Christiane E, Al-Hussaini, Hamoud HY, Ali, Amany M, Alia, Donjeta B, Al-Jadiry, Mazin F, Al-Jumaily, Usama, Alkatan, Hind M, All-Eriksson, Charlotta, Al-Mafrachi, Ali ARM, Almeida, Argentino A, Alsawidi, Khalifa M, Al-Shaheen, Athar ASM, Al-Shammary, Entissar H, Amankwaa-Frempong, Doreen, Amiruddin, Primawita O, Armytasari, Inggar, Astbury, Nicholas J, Atalay, Hatice T, Ataseven, Eda, Atchaneeyasakul, La-ongsri, Atsiaya, Rose, Autrata, Rudolf, Balaguer, Julia, Balayeva, Ruhengiz, Barranco, Honorio, Bartoszek, Paulina, Bartuma, Katarina, Bascaran, Covadonga, Bechrakis, Nikolaos E, Beck Popovic, Maja, Begimkulova, Ainura S, Benmiloud, Sarra, Berete, Rokia C, Berry, Jesse L, Bhaduri, Anirban, Bhat, Sunil, Bhattacharyya, Arpita, Biewald, Eva M, Binkley, Elaine, Blum, Sharon, Bobrova, Nadia, Boldt, H.C., Bonanomi, Maria Teresa BC, Bouda, Gabrielle C, Bouguila, Hédi, Brennan, Rachel C, Brichard, Bénédicte G, Buaboonnam, Jassada, Budiongo, Aléine, Burton, Matthew J, Calderón-Sotelo, Patricia, Calle Jara, Doris A, Camuglia, Jayne E, Cano, Miriam R, Capra, Michael, Caspi, Shani, Cassoux, Nathalie, Castela, Guilherme, Castillo, Luis, Català-Mora, Jaume, Cavieres, Isabel, Chandramohan, Arthika, Chantada, Guillermo L, Chaudhry, Shabana, Chawla, Bhavna, Chen, Wensi, Chiwanga, Faraja S, Chuluunbat, Tsengelmaa, Cieslik, Krzysztof, Clark, Antony, Cockcroft, Ruellyn L, Comsa, Codruta, Correa Llano, Maria G, Corson, Timothy W, Couitchere, Line, Cowan-Lyn, Kristin E, Csóka, Monika, Dangboon, Wantanee, Das, Anirban, Das, Pranab, Das, Sima, Davanzo, Jacquelyn M, Davidson, Alan, De Francesco, Sonia, De Potter, Patrick, Quintero D, Karina, Demirci, Hakan, Desjardins, Laurence, Díaz Coronado, Rosdali Y, Dimaras, Helen, Dodgshun, Andrew J, Donato Macedo, Carla R, Dragomir, Monica D, Du, Yi, Du Bruyn, Magritha, Du Plessis, Johannes, Dudeja, Gagan, Eerme, Katrin, Eka Sutyawan, I Wayan, El Kettani, Asmaa, Elbahi, Amal M, Elder, James E, Elhaddad, Alaa M, Elhassan, Moawia MA, Elzembely, Mahmoud M, Ericksen, Connor, Essuman, Vera A, Evina, Ted Grimbert A, Ezegwui, Ifeoma R, Fadoo, Zehra, Fandiño, Adriana C, Faranoush, Mohammad, Fasina, Oluyemi, Fernández, Delia DPG, Fernández-Teijeiro, Ana, Foster, Allen, Frenkel, Shahar, Fu, Ligia D, Fuentes-Alabi, Soad L, Garcia, Juan L, García Aldana, David, Garcia Pacheco, Henry N, Geel, Jennifer A, Ghassemi, Fariba, Girón, Ana V, Goenz, Marco A, Gold, Aaron S, Goldberg, Hila, Gole, Glen A, Gomel, Nir, Gonzalez, Efren, Gonzalez Perez, Graciela, González-Rodríguez, Liudmira, Gorfine, Malka, Graells, Jaime, Gregersen, Pernille A, Grigorovski, Nathalia DAK, Guedenon, Koffi M, Gunasekera, D Sanjeeva, Gündüz, Ahmet K, Gupta, Himika, Gupta, Sanjiv, Gupta, Vineeta, Hadjistilianou, Theodora, Hamel, Patrick, Hamid, Syed A, Hamzah, Norhafizah, Hansen, Eric D, Harbour, J William, Hartnett, M. Elizabeth, Hasanreisoglu, Murat, Muhammad, Hassan, Hassan, Sadiq, Hassan, Shadab, Hautz, Wojciech, Haydar, Huda, Hederova, Stanislava, Hessissen, Laila, Hongeng, Suradej, Hordofa, Diriba F, Hubbard, G. Baker, Hummelen, Marlies, Husakova, Kristina, Hussein Al-Janabi, Allawi N, Ibanga, Affiong, Ida, Russo, Ilic, Vesna R, Islamov, Ziyavuddin, Jairaj, Vivekaraj, Janjua, Teyyeb, Jeeva, Irfan, Ji, Xunda, Jo, Dong Hyun, Jones, Michael M, Kabesha Amani, Theophile B, Kabore, Rolande L, Kaliki, Swathi, Kalinaki, Abubakar, Kamsang, Pius, Kantar, Mehmet, Kapelushnik, Noa, Kardava, Tamar, Kebudi, Rejin, Keomisy, Jonny, Kepak, Tomas, Ketteler, Petra, Khan, Zohora J, Khaqan, Hussain A, Khetan, Vikas, Khodabande, Alireza, Khotenashvili, Zaza, Kim, Jonathan W, Kim, Jeong Hun, Kiratli, Hayyam, Kivela, Tero T., Klett, Artur, Koç, Irem, Kosh Komba Palet, Jess Elio, Krivaitiene, Dalia, Kruger, Mariana, Kulvichit, Kittisak, Kuntorini, Mayasari W, Kyara, Alice, Lam, Geoffrey C, Larson, Scott A, Latinović, Slobodanka, Laurenti, Kelly D, Lavy, Yotam, Lavric Groznik, Alenka, Leverant, Amy A, Li, Cairui, Li, Kaijun, Limbu, Ben, Liu, Chun-Hsiu, Quah, BoonLong, López, Juan P, Lukamba, Robert M, Luna-Fineman, Sandra, Lutfi, Delfitri, Lysytsia, Lesia, Madgar, Shiran, Magrath, George N, Mahajan, Amita, Maitra, Puja, Maka, Erika, Makimbetov, Emil K, Maktabi, Azza, Maldonado, Carlos, Mallipatna, Ashwin, Manudhane, Rebecca, Manzhuova, Lyazat, Martín-Begue, Nieves, Masud, Sidra, Matende, Ibrahim O, Mattosinho, Clarissa CDS, Matua, Marchelo, Mayet, Ismail, Mbumba, Freddy B, McKenzie, John D, Mehrvar, Azim, Mengesha, Aemero A, Menon, Vikas, Mercado, Gary John V, Mets, Marilyn B, Midena, Edoardo, Miller, Audra, Mishra, Divyansh KC, Mndeme, Furahini G, Mohamedani, Ahmed A, Mohammad, Mona T, Moll, Annette C, Montero, Margarita M, Moreira, Claude, Mruthyunjaya, Prithvi, Msina, Mchikirwa S, Msukwa, Gerald, Mudaliar, Sangeeta S, Muma, Kangwa I M, Munier, Francis L, Murray, Timothy G, Musa, Kareem O, Mushtaq, Asma, Musika, Anne A, Mustak, Hamzah, Mustapha, Tajudeen, Muyen, Okwen M, Myezo, Khumo H, Naidu, Gita, Naidu, Natasha, Nair, Akshay Gopinathan, Natarajan, Sundaram, Naumenko, Larisa, Ndoye Roth, Paule Aïda, Nency, Yetty M, Neroev, Vladimir, Ng, Yvonne, Nikitovic, Marina, Nkanga, Elizabeth D, Nkumbe, Henry E, Numbi, Marcel N, Nummi, Kalle, Nuruddin, Murtuza, Nyaywa, Mutale, Nyirenda, Chinsisi, Obono-Obiang, Ghislaine, Oliver, Scott CN, Oporto, Joaquin, Ortega-Hernández, Miriam, Oscar, Alexander H, Ossandon, Diego, Pagarra, Halimah, Paintsil, Vivian, Paiva, Luisa, Palanivelu, Mahesh Shanmugam, Papyan, Ruzanna, Parrozzani, Raffaele, Pascual Morales, Claudia R, Paton, Katherine E, Pe'er, Jacob, Peralta Calvo, Jesús, Perić, Sanja, Pham, Chau TM, Philbert, Remezo, Plager, David A, Pochop, Pavel, Polania, Rodrigo A., Polyakov, Vladimir, Ponce, Jimena, Qadir, Ali O, Qayyum, Seema, Qian, Jiang, Refaeli, David, Rahman, Ardizal, Rajkarnikar, Purnima, Ramanjulu, Rajesh, Ramasubramanian, Aparna, Ramirez-Ortiz, Marco A, Randhawa, Jasmeen K, Randrianarisoa, Hoby Lalaina, Raobela, Léa, Rashid, Riffat, Reddy, M.A., Renner, Lorna A, Reynders, David, Ribadu, Dahiru, Ritter-Sovinz, Petra, Rogowska, Anna, Rojanaporn, Duangnate, Romero, Livia, Roy, Soma R, Saab, Raya H, Saakyan, Svetlana, Sabhan, Ahmed H, Sagoo, Mandeep S, Said, Azza MA, Saiju, Rohit, Salas, Beatriz, San Román Pacheco, Sonsoles, Sánchez, Gissela L, Sanchez Orozco, Alma Janeth, Sayalith, Phayvanh, Scanlan, Trish A, Schlüter, Sabrina, Schwab, Christoph, Sedaghat, Ahad, Seth, Rachna, Sgroi, Mariana, Shah, Ankoor S, Shakoor, Shawkat A, Sharma, Manoj K, Sherief, Sadik T, Shields, Carol L, Sia, David, Siddiqui, Sorath Noorani, Sidi cheikh, Sidi, Silva, Sónia, Singh, Arun D, Singh, Usha, Singha, Penny, Sitorus, Rita S, Skalet, Alison H, Soebagjo, Hendrian D, Sorochynska, Tetyana, Ssali, Grace, Stacey, Andrew W, Staffieri, Sandra E, Stahl, Erin D, Steinberg, David M, Stones, David K, Strahlendorf, Caron, Suarez, Maria Estela Coleoni, Sultana, Sadia, Sun, Xiantao, Superstein, Rosanne, Supriyadi, Eddy, Surukrattanaskul, Supawan, Suzuki, Shigenobu, Svojgr, Karel, Sylla, Fatoumata, Tamamyan, Gevorg, Tan, Deborah, Tandili, Alketa, Tang, Jing, Tarrillo Leiva, Fanny F, Tashvighi, Maryam, Tateshi, Bekim, Teh, Kok Hoi, Tehuteru, Edi S, Teixeira, Luiz F, Tekavcic Pompe, Manca, Thawaba, Abdullah Dahan M, Theophile, Tuyisabe, Toledano, Helen, Trang, Doan L, Traoré, Fousseyni, Tripathy, Devjyoti, Tuncer, Samuray, Tyau-Tyau, Harba, Umar, Ali B, Unal, Emel, Uner, Ogul E, Urbak, Steen F, Ushakova, Tatiana L, Usmanov, Rustam H, Valeina, Sandra, Valente, Paola, van Hoefen Wijsard, Milo, Vasquez Anchaya, Jacqueline Karina, Vaughan, Leon O, Veleva-Krasteva, Nevyana V, Verma, Nishant, Victor, Andi A, Viksnins, Maris, Villacís Chafla, Edwin G, Villegas, Victor M, Vishnevskia-Dai, Victoria, Waddell, Keith, Wali, Amina H, Wang, Yi-Zhuo, Wangtiraumnuay, Nutsuchar, Wetter, Julie, Widiarti, Widiarti, Wilson, Matthew W, Wime, Amelia DC, Wiwatwongwana, Atchareeya, Wiwatwongwana, Damrong, Wolley Dod, Charlotte, Wong, Emily S, Wongwai, Phanthipha, Wu, Si-qi, Xiang, Daoman, Xiao, Yishuang, Xu, Bing, Xue, Kang, Yaghy, Antonio, Yam, Jason C, Yang, Huasheng, Yanga, Jenny M, Yaqub, Muhammad A, Yarovaya, Vera A, Yarovoy, Andrey A, Ye, Huijing, Yee, Roberto I, Yousef, Yacoub A, Yuliawati, Putu, Zapata López, Arturo M, Zein, Ekhtelbenina, Zhang, Yi, Zhilyaeva, Katsiaryna, Zia, Nida, Ziko, Othman AO, Zondervan, Marcia, and Bowman, Richard

Published
2022
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15. MIF/CXCR4 signaling axis contributes to survival, invasion, and drug resistance of metastatic neuroblastoma cells in the bone marrow microenvironment

Author

Garcia-Gerique, Laura, García, Marta, Garrido-Garcia, Alícia, Gómez-González, Soledad, Torrebadell, Montserrat, Prada, Estela, Pascual-Pasto, Guillem, Muñoz, Oscar, Perez-Jaume, Sara, Lemos, Isadora, Salvador, Noelia, Vila-Ubach, Monica, Doncel-Requena, Ana, Suñol, Mariona, Carcaboso, Angel M., Mora, Jaume, and Lavarino, Cinzia

Published
2022
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17. SPARC-mediated long-term retention of nab-paclitaxel in pediatric sarcomas

Author

Pascual-Pasto, Guillem, Castillo-Ecija, Helena, Unceta, Nora, Aschero, Rosario, Resa-Pares, Claudia, Gómez-Caballero, Alberto, Vila-Ubach, Monica, Muñoz-Aznar, Oscar, Suñol, Mariona, Burgueño, Victor, Gomez-Gonzalez, Soledad, Sosnik, Alejandro, Ibarra, Manuel, Schaiquevich, Paula, de Álava, Enrique, Tirado, Oscar M., Mora, Jaume, and Carcaboso, Angel M.

Published
2022
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18. Heterogeneity within the PF-EPN-B ependymoma subgroup

Author

Cavalli, Florence MG, Hübner, Jens-Martin, Sharma, Tanvi, Luu, Betty, Sill, Martin, Zapotocky, Michal, Mack, Stephen C, Witt, Hendrik, Lin, Tong, Shih, David JH, Ho, Ben, Santi, Mariarita, Emery, Lyndsey, Hukin, Juliette, Dunham, Christopher, McLendon, Roger E, Lipp, Eric S, Gururangan, Sridharan, Grossbach, Andrew, French, Pim, Kros, Johan M, van Veelen, Marie-Lise C, Rao, Amulya A Nageswara, Giannini, Caterina, Leary, Sarah, Jung, Shin, Faria, Claudia C, Mora, Jaume, Schüller, Ulrich, Alonso, Marta M, Chan, Jennifer A, Klekner, Almos, Chambless, Lola B, Hwang, Eugene I, Massimino, Maura, Eberhart, Charles G, Karajannis, Matthias A, Lu, Benjamin, Liau, Linda M, Zollo, Massimo, Ferrucci, Veronica, Carlotti, Carlos, Tirapelli, Daniela PC, Tabori, Uri, Bouffet, Eric, Ryzhova, Marina, Ellison, David W, Merchant, Thomas E, Gilbert, Mark R, Armstrong, Terri S, Korshunov, Andrey, Pfister, Stefan M, Taylor, Michael D, Aldape, Kenneth, Pajtler, Kristian W, Kool, Marcel, and Ramaswamy, Vijay

Subjects
Genetics, Cancer, Clinical Research, Rare Diseases, Human Genome, Brain Cancer, Brain Disorders, Adolescent, Adult, Age Factors, Child, Cohort Studies, DNA Copy Number Variations, DNA Methylation, Ependymoma, Female, Gene Expression Profiling, Humans, Infratentorial Neoplasms, Kaplan-Meier Estimate, Male, Microarray Analysis, Middle Aged, Young Adult, Posterior fossa, Subgrouping, PFB, PFA, Clustering, Clinical Sciences, Neurosciences, Neurology & Neurosurgery
Abstract

Posterior fossa ependymoma comprise three distinct molecular variants, termed PF-EPN-A (PFA), PF-EPN-B (PFB), and PF-EPN-SE (subependymoma). Clinically, they are very disparate and PFB tumors are currently being considered for a trial of radiation avoidance. However, to move forward, unraveling the heterogeneity within PFB would be highly desirable. To discern the molecular heterogeneity within PFB, we performed an integrated analysis consisting of DNA methylation profiling, copy-number profiling, gene expression profiling, and clinical correlation across a cohort of 212 primary posterior fossa PFB tumors. Unsupervised spectral clustering and t-SNE analysis of genome-wide methylation data revealed five distinct subtypes of PFB tumors, termed PFB1-5, with distinct demographics, copy-number alterations, and gene expression profiles. All PFB subtypes were distinct from PFA and posterior fossa subependymomas. Of the five subtypes, PFB4 and PFB5 are more discrete, consisting of younger and older patients, respectively, with a strong female-gender enrichment in PFB5 (age: p = 0.011, gender: p = 0.04). Broad copy-number aberrations were common; however, many events such as chromosome 2 loss, 5 gain, and 17 loss were enriched in specific subtypes and 1q gain was enriched in PFB1. Late relapses were common across all five subtypes, but deaths were uncommon and present in only two subtypes (PFB1 and PFB3). Unlike the case in PFA ependymoma, 1q gain was not a robust marker of poor progression-free survival; however, chromosome 13q loss may represent a novel marker for risk stratification across the spectrum of PFB subtypes. Similar to PFA ependymoma, there exists a significant intertumoral heterogeneity within PFB, with distinct molecular subtypes identified. Even when accounting for this heterogeneity, extent of resection remains the strongest predictor of poor outcome. However, this biological heterogeneity must be accounted for in future preclinical modeling and personalized therapies.

Published
2018

19. Origins of Second Malignancies in Children and Mutational Footprint of Chemotherapy in Normal Tissues

Author

Sánchez-Guixé, Mònica, primary, Muiños, Ferran, additional, Pinheiro-Santin, Morena, additional, González-Huici, Víctor, additional, Rodriguez-Hernandez, Carlos J., additional, Avgustinova, Alexandra, additional, Lavarino, Cinzia, additional, González-Pérez, Abel, additional, Mora, Jaume, additional, and López-Bigas, Núria, additional

Published
2024
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24. Selective inhibition of HDAC6 regulates expression of the oncogenic driver EWSR1-FLI1 through the EWSR1 promoter in Ewing sarcoma

Author

García-Domínguez, Daniel J., Hajji, Nabil, Sánchez-Molina, Sara, Figuerola-Bou, Elisabet, de Pablos, Rocío M., Espinosa-Oliva, Ana M., Andrés-León, Eduardo, Terrón-Camero, Laura Carmen, Flores-Campos, Rocío, Pascual-Pasto, Guillem, Robles, María José, Machado, Isidro, Llombart-Bosch, Antonio, Magagnoli, Giovanna, Scotlandi, Katia, Carcaboso, Ángel M., Mora, Jaume, de Álava, Enrique, and Hontecillas-Prieto, Lourdes

Published
2021
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25. The whole-genome landscape of medulloblastoma subtypes

Author

Northcott, Paul A, Buchhalter, Ivo, Morrissy, A Sorana, Hovestadt, Volker, Weischenfeldt, Joachim, Ehrenberger, Tobias, Gröbner, Susanne, Segura-Wang, Maia, Zichner, Thomas, Rudneva, Vasilisa A, Warnatz, Hans-Jörg, Sidiropoulos, Nikos, Phillips, Aaron H, Schumacher, Steven, Kleinheinz, Kortine, Waszak, Sebastian M, Erkek, Serap, Jones, David TW, Worst, Barbara C, Kool, Marcel, Zapatka, Marc, Jäger, Natalie, Chavez, Lukas, Hutter, Barbara, Bieg, Matthias, Paramasivam, Nagarajan, Heinold, Michael, Gu, Zuguang, Ishaque, Naveed, Jäger-Schmidt, Christina, Imbusch, Charles D, Jugold, Alke, Hübschmann, Daniel, Risch, Thomas, Amstislavskiy, Vyacheslav, Gonzalez, Francisco German Rodriguez, Weber, Ursula D, Wolf, Stephan, Robinson, Giles W, Zhou, Xin, Wu, Gang, Finkelstein, David, Liu, Yanling, Cavalli, Florence MG, Luu, Betty, Ramaswamy, Vijay, Wu, Xiaochong, Koster, Jan, Ryzhova, Marina, Cho, Yoon-Jae, Pomeroy, Scott L, Herold-Mende, Christel, Schuhmann, Martin, Ebinger, Martin, Liau, Linda M, Mora, Jaume, McLendon, Roger E, Jabado, Nada, Kumabe, Toshihiro, Chuah, Eric, Ma, Yussanne, Moore, Richard A, Mungall, Andrew J, Mungall, Karen L, Thiessen, Nina, Tse, Kane, Wong, Tina, Jones, Steven JM, Witt, Olaf, Milde, Till, Von Deimling, Andreas, Capper, David, Korshunov, Andrey, Yaspo, Marie-Laure, Kriwacki, Richard, Gajjar, Amar, Zhang, Jinghui, Beroukhim, Rameen, Fraenkel, Ernest, Korbel, Jan O, Brors, Benedikt, Schlesner, Matthias, Eils, Roland, Marra, Marco A, Pfister, Stefan M, Taylor, Michael D, and Lichter, Peter

Subjects
Cancer, Human Genome, Brain Disorders, Pediatric Cancer, Brain Cancer, Genetics, Biotechnology, Rare Diseases, Neurosciences, Pediatric, Aetiology, 2.1 Biological and endogenous factors, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Good Health and Well Being, Carcinogenesis, Carrier Proteins, Cohort Studies, DNA Methylation, DNA Mutational Analysis, Datasets as Topic, Epistasis, Genetic, Genome, Human, Genomics, Humans, Medulloblastoma, Molecular Targeted Therapy, Muscle Proteins, Mutation, Oncogenes, Transcription Factors, Whole Genome Sequencing, Wnt Proteins, General Science & Technology
Abstract

Current therapies for medulloblastoma, a highly malignant childhood brain tumour, impose debilitating effects on the developing child, and highlight the need for molecularly targeted treatments with reduced toxicity. Previous studies have been unable to identify the full spectrum of driver genes and molecular processes that operate in medulloblastoma subgroups. Here we analyse the somatic landscape across 491 sequenced medulloblastoma samples and the molecular heterogeneity among 1,256 epigenetically analysed cases, and identify subgroup-specific driver alterations that include previously undiscovered actionable targets. Driver mutations were confidently assigned to most patients belonging to Group 3 and Group 4 medulloblastoma subgroups, greatly enhancing previous knowledge. New molecular subtypes were differentially enriched for specific driver events, including hotspot in-frame insertions that target KBTBD4 and 'enhancer hijacking' events that activate PRDM6. Thus, the application of integrative genomics to an extensive cohort of clinical samples derived from a single childhood cancer entity revealed a series of cancer genes and biologically relevant subtype diversity that represent attractive therapeutic targets for the treatment of patients with medulloblastoma.

Published
2017

26. Intertumoral Heterogeneity within Medulloblastoma Subgroups

Author

Cavalli, Florence MG, Remke, Marc, Rampasek, Ladislav, Peacock, John, Shih, David JH, Luu, Betty, Garzia, Livia, Torchia, Jonathon, Nor, Carolina, Morrissy, A Sorana, Agnihotri, Sameer, Thompson, Yuan Yao, Kuzan-Fischer, Claudia M, Farooq, Hamza, Isaev, Keren, Daniels, Craig, Cho, Byung-Kyu, Kim, Seung-Ki, Wang, Kyu-Chang, Lee, Ji Yeoun, Grajkowska, Wieslawa A, Perek-Polnik, Marta, Vasiljevic, Alexandre, Faure-Conter, Cecile, Jouvet, Anne, Giannini, Caterina, Rao, Amulya A Nageswara, Li, Kay Ka Wai, Ng, Ho-Keung, Eberhart, Charles G, Pollack, Ian F, Hamilton, Ronald L, Gillespie, G Yancey, Olson, James M, Leary, Sarah, Weiss, William A, Lach, Boleslaw, Chambless, Lola B, Thompson, Reid C, Cooper, Michael K, Vibhakar, Rajeev, Hauser, Peter, van Veelen, Marie-Lise C, Kros, Johan M, French, Pim J, Ra, Young Shin, Kumabe, Toshihiro, López-Aguilar, Enrique, Zitterbart, Karel, Sterba, Jaroslav, Finocchiaro, Gaetano, Massimino, Maura, Van Meir, Erwin G, Osuka, Satoru, Shofuda, Tomoko, Klekner, Almos, Zollo, Massimo, Leonard, Jeffrey R, Rubin, Joshua B, Jabado, Nada, Albrecht, Steffen, Mora, Jaume, Van Meter, Timothy E, Jung, Shin, Moore, Andrew S, Hallahan, Andrew R, Chan, Jennifer A, Tirapelli, Daniela PC, Carlotti, Carlos G, Fouladi, Maryam, Pimentel, José, Faria, Claudia C, Saad, Ali G, Massimi, Luca, Liau, Linda M, Wheeler, Helen, Nakamura, Hideo, Elbabaa, Samer K, Perezpeña-Diazconti, Mario, de León, Fernando Chico Ponce, Robinson, Shenandoah, Zapotocky, Michal, Lassaletta, Alvaro, Huang, Annie, Hawkins, Cynthia E, Tabori, Uri, Bouffet, Eric, Bartels, Ute, Dirks, Peter B, Rutka, James T, Bader, Gary D, Reimand, Jüri, Goldenberg, Anna, Ramaswamy, Vijay, and Taylor, Michael D

Subjects
Genetics, Rare Diseases, Pediatric Cancer, Cancer, Brain Cancer, Pediatric Research Initiative, Pediatric, Human Genome, Brain Disorders, Cluster Analysis, Cohort Studies, DNA Copy Number Variations, DNA Methylation, Gene Expression Profiling, Genomics, Humans, Medulloblastoma, Precision Medicine, copy number, gene expression, integrative clustering, medulloblastoma, methylation, subgroups, Neurosciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

While molecular subgrouping has revolutionized medulloblastoma classification, the extent of heterogeneity within subgroups is unknown. Similarity network fusion (SNF) applied to genome-wide DNA methylation and gene expression data across 763 primary samples identifies very homogeneous clusters of patients, supporting the presence of medulloblastoma subtypes. After integration of somatic copy-number alterations, and clinical features specific to each cluster, we identify 12 different subtypes of medulloblastoma. Integrative analysis using SNF further delineates group 3 from group 4 medulloblastoma, which is not as readily apparent through analyses of individual data types. Two clear subtypes of infants with Sonic Hedgehog medulloblastoma with disparate outcomes and biology are identified. Medulloblastoma subtypes identified through integrative clustering have important implications for stratification of future clinical trials.

Published
2017

31. Management of High-Risk Neuroblastoma with Soft-Tissue-Only Disease in the Era of Anti-GD2 Immunotherapy.

Author

Gorostegui, Maite, Muñoz, Juan Pablo, Perez-Jaume, Sara, Simao-Rafael, Margarida, Larrosa, Cristina, Garraus, Moira, Salvador, Noelia, Lavarino, Cinzia, Krauel, Lucas, Mañe, Salvador, Castañeda, Alicia, and Mora, Jaume

Subjects
THERAPEUTIC use of antineoplastic agents, THERAPEUTIC use of monoclonal antibodies, CANCER relapse, IMMUNOTHERAPY, TREATMENT effectiveness, CANCER patients, RETROSPECTIVE studies, DESCRIPTIVE statistics, CANCER chemotherapy, SOFT tissue tumors, COMPARATIVE studies, NEUROBLASTOMA, PROPORTIONAL hazards models
Abstract

Simple Summary: Neuroblastoma (NB) presents with two patterns of disease: with or without metastasis. Both types of disease presentation include tumors with high-risk (HR) features. The management of HR-NB includes chemotherapy, surgery, radiotherapy, and anti-GD2 immunotherapy. Anti-GD2 monoclonal antibodies (mAbs) have significantly improved the outcome of HR-NB patients but they are mostly effective against disease affecting the bone and/or bone marrow (known as the osteomedullary compartment), and less so against soft tissue disease. The question arises as to whether anti-GD2 immunotherapy might benefit HR-NB patients with disease compounded by only soft tissue. In this retrospective review, we found that achieving first complete remission with chemotherapy, surgery, and radiotherapy does not prevent the risk of relapse. However, adding anti-GD2 mAbs once the patient has achieved complete remission significantly decreases the chances of relapse by 80%. Our study provides further support to indicate anti-GD2 mAbs in all cases with HR-NB. Neuroblastoma presents with two patterns of disease: locoregional or systemic. The poor prognostic risk factors of locoregional neuroblastoma (LR-NB) include age, MYCN or MDM2-CDK4 amplification, 11q, histology, diploidy with ALK or TERT mutations, and ATRX aberrations. Anti-GD2 immunotherapy has significantly improved the outcome of high-risk (HR) NB and is mostly effective against osteomedullary minimal residual disease (MRD), but less so against soft tissue disease. The question is whether adding anti-GD2 monoclonal antibodies (mAbs) benefits patients with HR-NB compounded by only soft tissue. We reviewed 31 patients treated at SJD for HR-NB with no osteomedullary involvement at diagnosis. All tumors had molecular genetic features of HR-NB. The outcome after first-line treatment showed 25 (80.6%) patients achieving CR. Thirteen patients remain in continued CR, median follow-up 3.9 years. We analyzed whether adding anti-GD2 immunotherapy to first-line treatment had any prognostic significance. The EFS analysis using Cox models showed a HR of 0.20, p = 0.0054, and an 80% decrease in the risk of relapse in patients treated with anti-GD2 immunotherapy in the first line. Neither EFS nor OS were significantly different by CR status after first-line treatment. In conclusion, adding treatment with anti-GD2 mAbs at the stage of MRD helps prevent relapse that unequivocally portends poor survival. [ABSTRACT FROM AUTHOR]

Published
2024
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32. GM‐CSF, G‐CSF or no cytokine therapy with anti‐GD2 immunotherapy for high‐risk neuroblastoma.

Author

Mora, Jaume, Modak, Shakeel, Kinsey, Joyce, Ragsdale, Carolyn E., and Lazarus, Hillard M.

Abstract

Colony‐stimulating factors have been shown to improve anti‐disialoganglioside 2 (anti‐GD2) monoclonal antibody response in high‐risk neuroblastoma by enhancing antibody‐dependent cell‐mediated cytotoxicity (ADCC). A substantial amount of research has focused on recombinant human granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) as an adjuvant to anti‐GD2 monoclonal antibodies. There may be a disparity in care among patients as access to GM‐CSF therapy and anti‐GD2 monoclonal antibodies is not uniform. Only select countries have approved these agents for use, and even with regulatory approvals, access to these agents can be complex and cost prohibitive. This comprehensive review summarizes clinical data regarding efficacy and safety of GM‐CSF, recombinant human granulocyte colony‐stimulating factor (G‐CSF) or no cytokine in combination with anti‐GD2 monoclonal antibodies (ie, dinutuximab, dinutuximab beta or naxitamab) for immunotherapy of patients with high‐risk neuroblastoma. A substantial body of clinical data support the immunotherapy combination of anti‐GD2 monoclonal antibodies and GM‐CSF. In contrast, clinical data supporting the use of G‐CSF are limited. No formal comparison between GM‐CSF, G‐CSF and no cytokine has been identified. The treatment of high‐risk neuroblastoma with anti‐GD2 therapy plus GM‐CSF is well established. Suboptimal efficacy outcomes with G‐CSF raise concerns about its suitability as an alternative to GM‐CSF as an adjuvant in immunotherapy for patients with high‐risk neuroblastoma. While programs exist to facilitate obtaining GM‐CSF and anti‐GD2 monoclonal antibodies in regions where they are not commercially available, continued work is needed to ensure equitable therapeutic options are available globally. [ABSTRACT FROM AUTHOR]

Published
2024
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33. Author Correction: Failure of human rhombic lip differentiation underlies medulloblastoma formation

Author

Hendrikse, Liam D., Haldipur, Parthiv, Saulnier, Olivier, Millman, Jake, Sjoboen, Alexandria H., Erickson, Anders W., Ong, Winnie, Gordon, Victor, Coudière-Morrison, Ludivine, Mercier, Audrey L., Shokouhian, Mohammad, Suárez, Raúl A., Ly, Michelle, Borlase, Stephanie, Scott, David S., Vladoiu, Maria C., Farooq, Hamza, Sirbu, Olga, Nakashima, Takuma, Nambu, Shohei, Funakoshi, Yusuke, Bahcheli, Alec, Diaz-Mejia, J. Javier, Golser, Joseph, Bach, Kathleen, Phuong-Bao, Tram, Skowron, Patryk, Wang, Evan Y., Kumar, Sachin A., Balin, Polina, Visvanathan, Abhirami, Lee, John J. Y., Ayoub, Ramy, Chen, Xin, Chen, Xiaodi, Mungall, Karen L., Luu, Betty, Bérubé, Pierre, Wang, Yu C., Pfister, Stefan M., Kim, Seung-Ki, Delattre, Olivier, Bourdeaut, Franck, Doz, François, Masliah-Planchon, Julien, Grajkowska, Wieslawa A., Loukides, James, Dirks, Peter, Fèvre-Montange, Michelle, Jouvet, Anne, French, Pim J., Kros, Johan M., Zitterbart, Karel, Bailey, Swneke D., Eberhart, Charles G., Rao, Amulya A. N., Giannini, Caterina, Olson, James M., Garami, Miklós, Hauser, Peter, Phillips, Joanna J., Ra, Young S., de Torres, Carmen, Mora, Jaume, Li, Kay K. W., Ng, Ho-Keung, Poon, Wai S., Pollack, Ian F., López-Aguilar, Enrique, Gillespie, G. Yancey, Van Meter, Timothy E., Shofuda, Tomoko, Vibhakar, Rajeev, Thompson, Reid C., Cooper, Michael K., Rubin, Joshua B., Kumabe, Toshihiro, Jung, Shin, Lach, Boleslaw, Iolascon, Achille, Ferrucci, Veronica, de Antonellis, Pasqualino, Zollo, Massimo, Cinalli, Giuseppe, Robinson, Shenandoah, Stearns, Duncan S., Van Meir, Erwin G., Porrati, Paola, Finocchiaro, Gaetano, Massimino, Maura, Carlotti, Carlos G., Faria, Claudia C., Roussel, Martine F., Boop, Frederick, Chan, Jennifer A., Aldinger, Kimberly A., Razavi, Ferechte, Silvestri, Evelina, McLendon, Roger E., Thompson, Eric M., Ansari, Marc, Garre, Maria L., Chico, Fernando, Eguía, Pilar, Pérezpeña, Mario, Morrissy, A. Sorana, Cavalli, Florence M. G., Wu, Xiaochong, Daniels, Craig, Rich, Jeremy N., Jones, Steven J. M., Moore, Richard A., Marra, Marco A., Huang, Xi, Reimand, Jüri, Sorensen, Poul H., Wechsler-Reya, Robert J., Weiss, William A., Pugh, Trevor J., Garzia, Livia, Kleinman, Claudia L., Stein, Lincoln D., Jabado, Nada, Malkin, David, Ayrault, Olivier, Golden, Jeffrey A., Ellison, David W., Doble, Brad, Ramaswamy, Vijay, Werbowetski-Ogilvie, Tamra E., Suzuki, Hiromichi, Millen, Kathleen J., and Taylor, Michael D.

Published
2022
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34. Treatment-driven selection of chemoresistant Ewing sarcoma tumors with limited drug distribution

Author

Castillo-Ecija, Helena, Monterrubio, Carles, Pascual-Pasto, Guillem, Gomez-Gonzalez, Soledad, Garcia-Dominguez, Daniel J., Hontecillas-Prieto, Lourdes, Resa-Pares, Claudia, Burgueño, Victor, Paco, Sonia, Olaciregui, Nagore G., Vila-Ubach, Monica, Restrepo-Perdomo, Camilo, Cuadrado-Vilanova, Maria, Balaguer-Lluna, Leire, Perez-Jaume, Sara, Castañeda, Alicia, Santa-Maria, Vicente, Roldan, Monica, Suñol, Mariona, de Alava, Enrique, Mora, Jaume, Lavarino, Cinzia, and Carcaboso, Angel M.

Published
2020
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35. Therapeutic Impact of Cytoreductive Surgery and Irradiation of Posterior Fossa Ependymoma in the Molecular Era: A Retrospective Multicohort Analysis.

Author

Ramaswamy, Vijay, Hielscher, Thomas, Mack, Stephen C, Lassaletta, Alvaro, Lin, Tong, Pajtler, Kristian W, Jones, David TW, Luu, Betty, Cavalli, Florence MG, Aldape, Kenneth, Remke, Marc, Mynarek, Martin, Rutkowski, Stefan, Gururangan, Sridharan, McLendon, Roger E, Lipp, Eric S, Dunham, Christopher, Hukin, Juliette, Eisenstat, David D, Fulton, Dorcas, van Landeghem, Frank KH, Santi, Mariarita, van Veelen, Marie-Lise C, Van Meir, Erwin G, Osuka, Satoru, Fan, Xing, Muraszko, Karin M, Tirapelli, Daniela PC, Oba-Shinjo, Sueli M, Marie, Suely KN, Carlotti, Carlos G, Lee, Ji Yeoun, Rao, Amulya A Nageswara, Giannini, Caterina, Faria, Claudia C, Nunes, Sofia, Mora, Jaume, Hamilton, Ronald L, Hauser, Peter, Jabado, Nada, Petrecca, Kevin, Jung, Shin, Massimi, Luca, Zollo, Massimo, Cinalli, Giuseppe, Bognár, László, Klekner, Almos, Hortobágyi, Tibor, Leary, Sarah, Ermoian, Ralph P, Olson, James M, Leonard, Jeffrey R, Gardner, Corrine, Grajkowska, Wieslawa A, Chambless, Lola B, Cain, Jason, Eberhart, Charles G, Ahsan, Sama, Massimino, Maura, Giangaspero, Felice, Buttarelli, Francesca R, Packer, Roger J, Emery, Lyndsey, Yong, William H, Soto, Horacio, Liau, Linda M, Everson, Richard, Grossbach, Andrew, Shalaby, Tarek, Grotzer, Michael, Karajannis, Matthias A, Zagzag, David, Wheeler, Helen, von Hoff, Katja, Alonso, Marta M, Tuñon, Teresa, Schüller, Ulrich, Zitterbart, Karel, Sterba, Jaroslav, Chan, Jennifer A, Guzman, Miguel, Elbabaa, Samer K, Colman, Howard, Dhall, Girish, Fisher, Paul G, Fouladi, Maryam, Gajjar, Amar, Goldman, Stewart, Hwang, Eugene, Kool, Marcel, Ladha, Harshad, Vera-Bolanos, Elizabeth, Wani, Khalida, Lieberman, Frank, Mikkelsen, Tom, Omuro, Antonio M, Pollack, Ian F, Prados, Michael, Robins, H Ian, and Soffietti, Riccardo

Subjects
Humans, Ependymoma, Infratentorial Neoplasms, Combined Modality Therapy, Retrospective Studies, Cohort Studies, Adolescent, Adult, Child, Child, Preschool, Infant, Female, Male, Cytoreduction Surgical Procedures, Rare Diseases, Pediatric Cancer, Cancer, Pediatric, Patient Safety, Clinical Sciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

PurposePosterior fossa ependymoma comprises two distinct molecular variants termed EPN_PFA and EPN_PFB that have a distinct biology and natural history. The therapeutic value of cytoreductive surgery and radiation therapy for posterior fossa ependymoma after accounting for molecular subgroup is not known.MethodsFour independent nonoverlapping retrospective cohorts of posterior fossa ependymomas (n = 820) were profiled using genome-wide methylation arrays. Risk stratification models were designed based on known clinical and newly described molecular biomarkers identified by multivariable Cox proportional hazards analyses.ResultsMolecular subgroup is a powerful independent predictor of outcome even when accounting for age or treatment regimen. Incompletely resected EPN_PFA ependymomas have a dismal prognosis, with a 5-year progression-free survival ranging from 26.1% to 56.8% across all four cohorts. Although first-line (adjuvant) radiation is clearly beneficial for completely resected EPN_PFA, a substantial proportion of patients with EPN_PFB can be cured with surgery alone, and patients with relapsed EPN_PFB can often be treated successfully with delayed external-beam irradiation.ConclusionThe most impactful biomarker for posterior fossa ependymoma is molecular subgroup affiliation, independent of other demographic or treatment variables. However, both EPN_PFA and EPN_PFB still benefit from increased extent of resection, with the survival rates being particularly poor for subtotally resected EPN_PFA, even with adjuvant radiation therapy. Patients with EPN_PFB who undergo gross total resection are at lower risk for relapse and should be considered for inclusion in a randomized clinical trial of observation alone with radiation reserved for those who experience recurrence.

Published
2016

36. Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: a retrospective integrated clinical and molecular analysis

Author

Thompson, Eric M, Hielscher, Thomas, Bouffet, Eric, Remke, Marc, Luu, Betty, Gururangan, Sridharan, McLendon, Roger E, Bigner, Darell D, Lipp, Eric S, Perreault, Sebastien, Cho, Yoon-Jae, Grant, Gerald, Kim, Seung-Ki, Lee, Ji Yeoun, Rao, Amulya A Nageswara, Giannini, Caterina, Li, Kay Ka Wai, Ng, Ho-Keung, Yao, Yu, Kumabe, Toshihiro, Tominaga, Teiji, Grajkowska, Wieslawa A, Perek-Polnik, Marta, Low, David CY, Seow, Wan Tew, Chang, Kenneth TE, Mora, Jaume, Pollack, Ian F, Hamilton, Ronald L, Leary, Sarah, Moore, Andrew S, Ingram, Wendy J, Hallahan, Andrew R, Jouvet, Anne, Fèvre-Montange, Michelle, Vasiljevic, Alexandre, Faure-Conter, Cecile, Shofuda, Tomoko, Kagawa, Naoki, Hashimoto, Naoya, Jabado, Nada, Weil, Alexander G, Gayden, Tenzin, Wataya, Takafumi, Shalaby, Tarek, Grotzer, Michael, Zitterbart, Karel, Sterba, Jaroslav, Kren, Leos, Hortobágyi, Tibor, Klekner, Almos, László, Bognár, Pócza, Tímea, Hauser, Peter, Schüller, Ulrich, Jung, Shin, Jang, Woo-Youl, French, Pim J, Kros, Johan M, van Veelen, Marie-Lise C, Massimi, Luca, Leonard, Jeffrey R, Rubin, Joshua B, Vibhakar, Rajeev, Chambless, Lola B, Cooper, Michael K, Thompson, Reid C, Faria, Claudia C, Carvalho, Alice, Nunes, Sofia, Pimentel, José, Fan, Xing, Muraszko, Karin M, López-Aguilar, Enrique, Lyden, David, Garzia, Livia, Shih, David JH, Kijima, Noriyuki, Schneider, Christian, Adamski, Jennifer, Northcott, Paul A, Kool, Marcel, Jones, David TW, Chan, Jennifer A, Nikolic, Ana, Garre, Maria Luisa, Van Meir, Erwin G, Osuka, Satoru, Olson, Jeffrey J, Jahangiri, Arman, Castro, Brandyn A, Gupta, Nalin, Weiss, William A, Moxon-Emre, Iska, Mabbott, Donald J, Lassaletta, Alvaro, Hawkins, Cynthia E, Tabori, Uri, Drake, James, and Kulkarni, Abhaya

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Oncology and Carcinogenesis, Brain Disorders, Rare Diseases, Brain Cancer, Pediatric Research Initiative, Pediatric, Cancer, Adult, Brain Neoplasms, Canada, Child, Child, Preschool, Combined Modality Therapy, Disease Progression, Disease-Free Survival, Female, Humans, Infant, Magnetic Resonance Imaging, Male, Medulloblastoma, Prognosis, Retrospective Studies, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

BackgroundPatients with incomplete surgical resection of medulloblastoma are controversially regarded as having a marker of high-risk disease, which leads to patients undergoing aggressive surgical resections, so-called second-look surgeries, and intensified chemoradiotherapy. All previous studies assessing the clinical importance of extent of resection have not accounted for molecular subgroup. We analysed the prognostic value of extent of resection in a subgroup-specific manner.MethodsWe retrospectively identified patients who had a histological diagnosis of medulloblastoma and complete data about extent of resection and survival from centres participating in the Medulloblastoma Advanced Genomics International Consortium. We collected from resections done between April, 1997, and February, 2013, at 35 international institutions. We established medulloblastoma subgroup affiliation by gene expression profiling on frozen or formalin-fixed paraffin-embedded tissues. We classified extent of resection on the basis of postoperative imaging as gross total resection (no residual tumour), near-total resection (30 Gy vs no craniospinal irradiation). The primary analysis outcome was the effect of extent of resection by molecular subgroup and the effects of other clinical variables on overall and progression-free survival.FindingsWe included 787 patients with medulloblastoma (86 with WNT tumours, 242 with SHH tumours, 163 with group 3 tumours, and 296 with group 4 tumours) in our multivariable Cox models of progression-free and overall survival. We found that the prognostic benefit of increased extent of resection for patients with medulloblastoma is attenuated after molecular subgroup affiliation is taken into account. We identified a progression-free survival benefit for gross total resection over sub-total resection (hazard ratio [HR] 1·45, 95% CI 1·07-1·96, p=0·16) but no overall survival benefit (HR 1·23, 0·87-1·72, p=0·24). We saw no progression-free survival or overall survival benefit for gross total resection compared with near-total resection (HR 1·05, 0·71-1·53, p=0·8158 for progression-free survival and HR 1·14, 0·75-1·72, p=0·55 for overall survival). No significant survival benefit existed for greater extent of resection for patients with WNT, SHH, or group 3 tumours (HR 1·03, 0·67-1·58, p=0·89 for sub-total resection vs gross total resection). For patients with group 4 tumours, gross total resection conferred a benefit to progression-free survival compared with sub-total resection (HR 1·97, 1·22-3·17, p=0·0056), especially for those with metastatic disease (HR 2·22, 1·00-4·93, p=0·050). However, gross total resection had no effect on overall survival compared with sub-total resection in patients with group 4 tumours (HR 1·67, 0·93-2·99, p=0·084).InterpretationThe prognostic benefit of increased extent of resection for patients with medulloblastoma is attenuated after molecular subgroup affiliation is taken into account. Although maximum safe surgical resection should remain the standard of care, surgical removal of small residual portions of medulloblastoma is not recommended when the likelihood of neurological morbidity is high because there is no definitive benefit to gross total resection compared with near-total resection.FundingCanadian Cancer Society Research Institute, Terry Fox Research Institute, Canadian Institutes of Health Research, National Institutes of Health, Pediatric Brain Tumor Foundation, and the Garron Family Chair in Childhood Cancer Research.

Published
2016

37. Immunohistochemical expression of TFF1 is a marker of poor prognosis in retinoblastoma

Author

Aschero, Rosario, primary, Ganiewich, Daiana, additional, Lamas, Gabriela, additional, Restrepo‐Perdomo, Camilo A, additional, Ottaviani, Daniela, additional, Zugbi, Santiago, additional, Camarero, Sandra, additional, Néspoli, Ezequiel, additional, Vilanova, Maria Cuadrado, additional, Perez‐Jaume, Sara, additional, Pascual‐Pasto, Guillem, additional, Sampor, Claudia, additional, Grigorovski, Nathalia, additional, Salas, Beatriz, additional, Suñol, Mariona, additional, Carcaboso, Angel M., additional, Mora, Jaume, additional, de Dávila, María T G, additional, Doz, François, additional, Radvanyi, François, additional, Abramson, David H, additional, Llera, Andrea S, additional, Schaiquevich, Paula S, additional, Lubieniecki, Fabiana, additional, and Chantada, Guillermo L, additional

Published
2023
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38. Early Salvage Chemo-Immunotherapy with Irinotecan, Temozolomide and Naxitamab Plus GM-CSF (HITS) for Patients with Primary Refractory High-Risk Neuroblastoma Provide the Best Chance for Long-Term Outcomes

Author

Muñoz, Juan Pablo, primary, Larrosa, Cristina, additional, Chamorro, Saray, additional, Perez-Jaume, Sara, additional, Simao, Margarida, additional, Sanchez-Sierra, Nazaret, additional, Varo, Amalia, additional, Gorostegui, Maite, additional, Castañeda, Alicia, additional, Garraus, Moira, additional, Lopez-Miralles, Sandra, additional, and Mora, Jaume, additional

Published
2023
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40. Sarcoma classification by DNA methylation profiling

Author

Koelsche, Christian, Schrimpf, Daniel, Stichel, Damian, Sill, Martin, Sahm, Felix, Reuss, David E., Blattner, Mirjam, Worst, Barbara, Heilig, Christoph E., Beck, Katja, Horak, Peter, Kreutzfeldt, Simon, Paff, Elke, Stark, Sebastian, Johann, Pascal, Selt, Florian, Ecker, Jonas, Sturm, Dominik, Pajtler, Kristian W., Reinhardt, Annekathrin, Wefers, Annika K., Sievers, Philipp, Ebrahimi, Azadeh, Suwala, Abigail, Fernández-Klett, Francisco, Casalini, Belén, Korshunov, Andrey, Hovestadt, Volker, Kommoss, Felix K. F., Kriegsmann, Mark, Schick, Matthias, Bewerunge-Hudler, Melanie, Milde, Till, Witt, Olaf, Kulozik, Andreas E., Kool, Marcel, Romero-Pérez, Laura, Grünewald, Thomas G. P., Kirchner, Thomas, Wick, Wolfgang, Platten, Michael, Unterberg, Andreas, Uhl, Matthias, Abdollahi, Amir, Debus, Jürgen, Lehner, Burkhard, Thomas, Christian, Hasselblatt, Martin, Paulus, Werner, Hartmann, Christian, Staszewski, Ori, Prinz, Marco, Hench, Jürgen, Frank, Stephan, Versleijen-Jonkers, Yvonne M. H., Weidema, Marije E., Mentzel, Thomas, Griewank, Klaus, de Álava, Enrique, Martín, Juan Díaz, Gastearena, Miguel A. Idoate, Chang, Kenneth Tou-En, Low, Sharon Yin Yee, Cuevas-Bourdier, Adrian, Mittelbronn, Michel, Mynarek, Martin, Rutkowski, Stefan, Schüller, Ulrich, Mautner, Viktor F., Schittenhelm, Jens, Serrano, Jonathan, Snuderl, Matija, Büttner, Reinhard, Klingebiel, Thomas, Buslei, Rolf, Gessler, Manfred, Wesseling, Pieter, Dinjens, Winand N. M., Brandner, Sebastian, Jaunmuktane, Zane, Lyskjær, Iben, Schirmacher, Peter, Stenzinger, Albrecht, Brors, Benedikt, Glimm, Hanno, Heining, Christoph, Tirado, Oscar M., Sáinz-Jaspeado, Miguel, Mora, Jaume, Alonso, Javier, del Muro, Xavier Garcia, Moran, Sebastian, Esteller, Manel, Benhamida, Jamal K., Ladanyi, Marc, Wardelmann, Eva, Antonescu, Cristina, Flanagan, Adrienne, Dirksen, Uta, Hohenberger, Peter, Baumhoer, Daniel, Hartmann, Wolfgang, Vokuhl, Christian, Flucke, Uta, Petersen, Iver, Mechtersheimer, Gunhild, Capper, David, Jones, David T. W., Fröhling, Stefan, Pfister, Stefan M., and von Deimling, Andreas

Published
2021
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41. A high-risk retinoblastoma subtype with stemness features, dedifferentiated cone states and neuronal/ganglion cell gene expression

Author

Liu, Jing, Ottaviani, Daniela, Sefta, Meriem, Desbrousses, Céline, Chapeaublanc, Elodie, Aschero, Rosario, Sirab, Nanor, Lubieniecki, Fabiana, Lamas, Gabriela, Tonon, Laurie, Dehainault, Catherine, Hua, Clément, Fréneaux, Paul, Reichman, Sacha, Karboul, Narjesse, Biton, Anne, Mirabal-Ortega, Liliana, Larcher, Magalie, Brulard, Céline, Arrufat, Sandrine, Nicolas, André, Elarouci, Nabila, Popova, Tatiana, Némati, Fariba, Decaudin, Didier, Gentien, David, Baulande, Sylvain, Mariani, Odette, Dufour, Florent, Guibert, Sylvain, Vallot, Céline, Rouic, Livia Lumbroso-Le, Matet, Alexandre, Desjardins, Laurence, Pascual-Pasto, Guillem, Suñol, Mariona, Catala-Mora, Jaume, Llano, Genoveva Correa, Couturier, Jérôme, Barillot, Emmanuel, Schaiquevich, Paula, Gauthier-Villars, Marion, Stoppa-Lyonnet, Dominique, Golmard, Lisa, Houdayer, Claude, Brisse, Hervé, Bernard-Pierrot, Isabelle, Letouzé, Eric, Viari, Alain, Saule, Simon, Sastre-Garau, Xavier, Doz, François, Carcaboso, Angel M., Cassoux, Nathalie, Pouponnot, Celio, Goureau, Olivier, Chantada, Guillermo, de Reyniès, Aurélien, Aerts, Isabelle, and Radvanyi, François

Published
2021
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44. Epigenetic loss of RNA-methyltransferase NSUN5 in glioma targets ribosomes to drive a stress adaptive translational program

Author

Janin, Maxime, Ortiz-Barahona, Vanessa, de Moura, Manuel Castro, Martínez-Cardús, Anna, Llinàs-Arias, Pere, Soler, Marta, Nachmani, Daphna, Pelletier, Joffrey, Schumann, Ulrike, Calleja-Cervantes, Maria E., Moran, Sebastian, Guil, Sonia, Bueno-Costa, Alberto, Piñeyro, David, Perez-Salvia, Montserrat, Rosselló-Tortella, Margalida, Piqué, Laia, Bech-Serra, Joan J., De La Torre, Carolina, Vidal, August, Martínez-Iniesta, María, Martín-Tejera, Juan F., Villanueva, Alberto, Arias, Alexandra, Cuartas, Isabel, Aransay, Ana M., La Madrid, Andres Morales, Carcaboso, Angel M., Santa-Maria, Vicente, Mora, Jaume, Fernandez, Agustin F., Fraga, Mario F., Aldecoa, Iban, Pedrosa, Leire, Graus, Francesc, Vidal, Noemi, Martínez-Soler, Fina, Tortosa, Avelina, Carrato, Cristina, Balañá, Carme, Boudreau, Matthew W., Hergenrother, Paul J., Kötter, Peter, Entian, Karl-Dieter, Hench, Jürgen, Frank, Stephan, Mansouri, Sheila, Zadeh, Gelareh, Dans, Pablo D., Orozco, Modesto, Thomas, George, Blanco, Sandra, Seoane, Joan, Preiss, Thomas, Pandolfi, Pier Paolo, and Esteller, Manel

Published
2019
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45. Activating mutations in CSF1R and additional receptor tyrosine kinases in histiocytic neoplasms

Author

Durham, Benjamin H., Lopez Rodrigo, Estibaliz, Picarsic, Jennifer, Abramson, David, Rotemberg, Veronica, De Munck, Steven, Pannecoucke, Erwin, Lu, Sydney X., Pastore, Alessandro, Yoshimi, Akihide, Mandelker, Diana, Ceyhan-Birsoy, Ozge, Ulaner, Gary A., Walsh, Michael, Yabe, Mariko, Petrova-Drus, Kseniya, Arcila, Maria E., Ladanyi, Marc, Solit, David B., Berger, Michael F., Hyman, David M., Lacouture, Mario E., Erickson, Caroline, Saganty, Ruth, Ki, Michelle, Dunkel, Ira J., Santa-María López, Vicente, Mora, Jaume, Haroche, Julien, Emile, Jean-Francois, Decaux, Olivier, Geissmann, Frederic, Savvides, Savvas N., Drilon, Alexander, Diamond, Eli L., and Abdel-Wahab, Omar

Published
2019
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46. Long noncoding RNA EWSAT1-mediated gene repression facilitates Ewing sarcoma oncogenesis

Author

Howarth, Michelle Marques, Simpson, David, Ngok, Siu P, Nieves, Bethsaida, Chen, Ron, Siprashvili, Zurab, Vaka, Dedeepya, Breese, Marcus R, Crompton, Brian D, Alexe, Gabriela, Hawkins, Doug S, Jacobson, Damon, Brunner, Alayne L, West, Robert, Mora, Jaume, Stegmaier, Kimberly, Khavari, Paul, and Sweet-Cordero, E Alejandro

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Pediatric Cancer, Cancer, Human Genome, Pediatric, Biotechnology, Rare Diseases, Pediatric Research Initiative, Genetics, Aetiology, 2.1 Biological and endogenous factors, Cell Line, Tumor, Cell Transformation, Neoplastic, Down-Regulation, Gene Expression Regulation, Neoplastic, Heterogeneous-Nuclear Ribonucleoprotein K, Humans, Oncogene Proteins, Fusion, Proto-Oncogene Protein c-fli-1, RNA, Long Noncoding, RNA, Neoplasm, RNA-Binding Protein EWS, Ribonucleoproteins, Sarcoma, Ewing, Sequence Analysis, RNA, Up-Regulation, Medical and Health Sciences, Immunology, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Chromosomal translocation that results in fusion of the genes encoding RNA-binding protein EWS and transcription factor FLI1 (EWS-FLI1) is pathognomonic for Ewing sarcoma. EWS-FLI1 alters gene expression through mechanisms that are not completely understood. We performed RNA sequencing (RNAseq) analysis on primary pediatric human mesenchymal progenitor cells (pMPCs) expressing EWS-FLI1 in order to identify gene targets of this oncoprotein. We determined that long noncoding RNA-277 (Ewing sarcoma-associated transcript 1 [EWSAT1]) is upregulated by EWS-FLI1 in pMPCs. Inhibition of EWSAT1 expression diminished the ability of Ewing sarcoma cell lines to proliferate and form colonies in soft agar, whereas EWSAT1 inhibition had no effect on other cell types tested. Expression of EWS-FLI1 and EWSAT1 repressed gene expression, and a substantial fraction of targets that were repressed by EWS-FLI1 were also repressed by EWSAT1. Analysis of RNAseq data from primary human Ewing sarcoma further supported a role for EWSAT1 in mediating gene repression. We identified heterogeneous nuclear ribonucleoprotein (HNRNPK) as an RNA-binding protein that interacts with EWSAT1 and found a marked overlap in HNRNPK-repressed genes and those repressed by EWS-FLI1 and EWSAT1, suggesting that HNRNPK participates in EWSAT1-mediated gene repression. Together, our data reveal that EWSAT1 is a downstream target of EWS-FLI1 that facilitates the development of Ewing sarcoma via the repression of target genes.

Published
2014

47. Cytogenetic prognostication within medulloblastoma subgroups.

Author

Shih, David, Northcott, Paul, Remke, Marc, Korshunov, Andrey, Ramaswamy, Vijay, Kool, Marcel, Luu, Betty, Yao, Yuan, Wang, Xin, Dubuc, Adrian, Garzia, Livia, Peacock, John, Mack, Stephen, Wu, Xiaochong, Rolider, Adi, Morrissy, A, Cavalli, Florence, Jones, David, Zitterbart, Karel, Faria, Claudia, Schüller, Ulrich, Kren, Leos, Kumabe, Toshihiro, Tominaga, Teiji, Shin Ra, Young, Garami, Miklós, Hauser, Peter, Chan, Jennifer, Robinson, Shenandoah, Bognár, László, Klekner, Almos, Saad, Ali, Albrecht, Steffen, Fontebasso, Adam, Cinalli, Giuseppe, De Antonellis, Pasqualino, Zollo, Massimo, Cooper, Michael, Thompson, Reid, Bailey, Simon, Lindsey, Janet, Di Rocco, Concezio, Massimi, Luca, Michiels, Erna, Scherer, Stephen, Lee, Ji-Yeoun, Cho, Byung-Kyu, Kim, Seung-Ki, Wang, Kyu-Chang, Leonard, Jeffrey, Rubin, Joshua, de Torres, Carmen, Lavarino, Cinzia, Mora, Jaume, Cho, Yoon-Jae, Tabori, Uri, Olson, James, Gajjar, Amar, Packer, Roger, Fan, Xing, Muraszko, Karin, Vibhakar, Rajeev, Eberhart, Charles, Fouladi, Maryam, Lach, Boleslaw, Jung, Shin, Wechsler-Reya, Robert, Fèvre-Montange, Michelle, Jouvet, Anne, Jabado, Nada, Pollack, Ian, Rutkowski, Stefan, Pomeroy, Scott, French, Pim, Kloosterhof, Nanne, Kros, Johan, Van Meir, Erwin, Clifford, Steven, Bourdeaut, Franck, Delattre, Olivier, Doz, François, Hawkins, Cynthia, Malkin, David, Grajkowska, Wieslawa, Perek-Polnik, Marta, Bouffet, Eric, Rutka, James, Pfister, Stefan, Taylor, Michael, Gupta, Nalin, Phillips, Joanna, Weiss, William, and Liau, Linda

Subjects
Adolescent, Biomarkers, Tumor, Child, Child, Preschool, Chromosomes, Human, Pair 11, Chromosomes, Human, Pair 14, Cytogenetics, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Hedgehog Proteins, Humans, In Situ Hybridization, Fluorescence, Infant, Kruppel-Like Transcription Factors, Male, Medulloblastoma, Nuclear Proteins, Predictive Value of Tests, Prognosis, Proportional Hazards Models, Proto-Oncogene Proteins c-myc, Reproducibility of Results, Risk Assessment, Risk Factors, Tissue Array Analysis, Wnt Proteins, Young Adult, Zinc Finger Protein Gli2
Abstract

PURPOSE: Medulloblastoma comprises four distinct molecular subgroups: WNT, SHH, Group 3, and Group 4. Current medulloblastoma protocols stratify patients based on clinical features: patient age, metastatic stage, extent of resection, and histologic variant. Stark prognostic and genetic differences among the four subgroups suggest that subgroup-specific molecular biomarkers could improve patient prognostication. PATIENTS AND METHODS: Molecular biomarkers were identified from a discovery set of 673 medulloblastomas from 43 cities around the world. Combined risk stratification models were designed based on clinical and cytogenetic biomarkers identified by multivariable Cox proportional hazards analyses. Identified biomarkers were tested using fluorescent in situ hybridization (FISH) on a nonoverlapping medulloblastoma tissue microarray (n = 453), with subsequent validation of the risk stratification models. RESULTS: Subgroup information improves the predictive accuracy of a multivariable survival model compared with clinical biomarkers alone. Most previously published cytogenetic biomarkers are only prognostic within a single medulloblastoma subgroup. Profiling six FISH biomarkers (GLI2, MYC, chromosome 11 [chr11], chr14, 17p, and 17q) on formalin-fixed paraffin-embedded tissues, we can reliably and reproducibly identify very low-risk and very high-risk patients within SHH, Group 3, and Group 4 medulloblastomas. CONCLUSION: Combining subgroup and cytogenetic biomarkers with established clinical biomarkers substantially improves patient prognostication, even in the context of heterogeneous clinical therapies. The prognostic significance of most molecular biomarkers is restricted to a specific subgroup. We have identified a small panel of cytogenetic biomarkers that reliably identifies very high-risk and very low-risk groups of patients, making it an excellent tool for selecting patients for therapy intensification and therapy de-escalation in future clinical trials.

Published
2014

48. Immunohistochemical expression of TFF1 is a marker of poor prognosis in retinoblastoma.

Author

Aschero, Rosario, Ganiewich, Daiana, Lamas, Gabriela, Restrepo-Perdomo, Camilo A., Ottaviani, Daniela, Zugbi, Santiago, Camarero, Sandra, Néspoli, Ezequiel, Vilanova, Maria Cuadrado, Perez-Jaume, Sara, Pascual-Pasto, Guillem, Sampor, Claudia, Grigorovski, Nathalia, Salas, Beatriz, Suñol, Mariona, Carcaboso, Angel M., Mora, Jaume, de Dávila, María T. G., Doz, François, and Radvanyi, François

Published
2024
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49. Immunohistochemical expression of TFF1 is a new prognostic marker in retinoblastoma

Author

Aschero, Rosario, primary, Ganiewich, Daiana, additional, Lamas, Gabriela, additional, Restrepo-Perdomo, Camilo A, additional, Ottaviani, Daniela, additional, Zugbi, Santiago, additional, Camarero, Sandra, additional, Néspoli, Ezequiel, additional, Vilanova, Maria Cuadrado, additional, Perez-Jaume, Sara, additional, Pascual-Pasto, Guillem, additional, Sampor, Claudia, additional, Grigorovski, Nathalia, additional, Salas, Beatriz, additional, Suñol, Mariona, additional, Carcaboso, Angel M., additional, Mora, Jaume, additional, de Dávila, María T G, additional, Doz, François, additional, Radvanyi, François, additional, Abramson, David H, additional, Llera, Andrea S, additional, Schaiquevich, Paula S, additional, Lubieniecki, Fabiana, additional, and Chantada, Guillermo L, additional

Published
2023
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