Search

Your search keyword '"Genovese, Giannicola"' showing total 325 results
Start Over Author "Genovese, Giannicola"
325 results on '"Genovese, Giannicola"'

1. Mitochondrial complex I promotes kidney cancer metastasis

Author

Bezwada, Divya, Perelli, Luigi, Lesner, Nicholas P., Cai, Ling, Brooks, Bailey, Wu, Zheng, Vu, Hieu S., Sondhi, Varun, Cassidy, Daniel L., Kasitinon, Stacy, Kelekar, Sherwin, Cai, Feng, Aurora, Arin B., Patrick, McKenzie, Leach, Ashley, Ghandour, Rashed, Zhang, Yuanyuan, Do, Duyen, McDaniel, Phyllis, Sudderth, Jessica, Dumesnil, Dennis, House, Sara, Rosales, Tracy, Poole, Alan M., Lotan, Yair, Woldu, Solomon, Bagrodia, Aditya, Meng, Xiaosong, Cadeddu, Jeffrey A., Mishra, Prashant, Garcia-Bermudez, Javier, Pedrosa, Ivan, Kapur, Payal, Courtney, Kevin D., Malloy, Craig R., Genovese, Giannicola, Margulis, Vitaly, and DeBerardinis, Ralph J.

Published
2024
Full Text
View/download PDF

2. Ether phospholipids are required for mitochondrial reactive oxygen species homeostasis

Author

Chen, Ziheng, Ho, I-Lin, Soeung, Melinda, Yen, Er-Yen, Liu, Jintan, Yan, Liang, Rose, Johnathon L., Srinivasan, Sanjana, Jiang, Shan, Edward Chang, Q., Feng, Ningping, Gay, Jason P., Wang, Qi, Wang, Jing, Lorenzi, Philip L., Veillon, Lucas J., Wei, Bo, Weinstein, John N., Deem, Angela K., Gao, Sisi, Genovese, Giannicola, Viale, Andrea, Yao, Wantong, Lyssiotis, Costas A., Marszalek, Joseph R., Draetta, Giulio F., and Ying, Haoqiang

Published
2023
Full Text
View/download PDF

3. Interferon signaling promotes tolerance to chromosomal instability during metastatic evolution in renal cancer

Author

Perelli, Luigi, Carbone, Federica, Zhang, Li, Huang, Justin K., Le, Courtney, Khan, Hania, Citron, Francesca, Del Poggetto, Edoardo, Gutschner, Tony, Tomihara, Hideo, Soeung, Melinda, Minelli, Rosalba, Srinivasan, Sanjana, Peoples, Michael, Lam, Truong Nguyen Anh, Lundgren, Sebastian, Xia, Ruohan, Zhu, Cihui, Mohamed, Alaa M. T., Zhang, Jianhua, Sircar, Kanishka, Sgambato, Alessandro, Gao, JianJun, Jonasch, Eric, Draetta, Giulio F., Futreal, Andrew, Bakouny, Ziad, Van Allen, Eliezer M., Choueiri, Toni, Signoretti, Sabina, Msaouel, Pavlos, Litchfield, Kevin, Turajlic, Samra, Wang, Linghua, Chen, Ying Bei, Di Natale, Renzo G., Hakimi, A. Ari, Giuliani, Virginia, Heffernan, Timothy P., Viale, Andrea, Bristow, Christopher A., Tannir, Nizar M., Carugo, Alessandro, and Genovese, Giannicola

Published
2023
Full Text
View/download PDF

4. PRMT1-dependent regulation of RNA metabolism and DNA damage response sustains pancreatic ductal adenocarcinoma.

Author

Giuliani, Virginia, Miller, Meredith A, Liu, Chiu-Yi, Hartono, Stella R, Class, Caleb A, Bristow, Christopher A, Suzuki, Erika, Sanz, Lionel A, Gao, Guang, Gay, Jason P, Feng, Ningping, Rose, Johnathon L, Tomihara, Hideo, Daniele, Joseph R, Peoples, Michael D, Bardenhagen, Jennifer P, Geck Do, Mary K, Chang, Qing E, Vangamudi, Bhavatarini, Vellano, Christopher, Ying, Haoqiang, Deem, Angela K, Do, Kim-Anh, Genovese, Giannicola, Marszalek, Joseph R, Kovacs, Jeffrey J, Kim, Michael, Fleming, Jason B, Guccione, Ernesto, Viale, Andrea, Maitra, Anirban, Emilia Di Francesco, M, Yap, Timothy A, Jones, Philip, Draetta, Giulio, Carugo, Alessandro, Chedin, Frederic, and Heffernan, Timothy P

Subjects
Cell Line, Tumor, Animals, Mice, Inbred NOD, Mice, Knockout, Humans, Mice, SCID, Carcinoma, Pancreatic Ductal, Pancreatic Neoplasms, DNA Damage, Repressor Proteins, RNA, Enzyme Inhibitors, Tumor Burden, Xenograft Model Antitumor Assays, Cell Proliferation, RNA Interference, Female, Biocatalysis, Protein-Arginine N-Methyltransferases
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer that has remained clinically challenging to manage. Here we employ an RNAi-based in vivo functional genomics platform to determine epigenetic vulnerabilities across a panel of patient-derived PDAC models. Through this, we identify protein arginine methyltransferase 1 (PRMT1) as a critical dependency required for PDAC maintenance. Genetic and pharmacological studies validate the role of PRMT1 in maintaining PDAC growth. Mechanistically, using proteomic and transcriptomic analyses, we demonstrate that global inhibition of asymmetric arginine methylation impairs RNA metabolism, which includes RNA splicing, alternative polyadenylation, and transcription termination. This triggers a robust downregulation of multiple pathways involved in the DNA damage response, thereby promoting genomic instability and inhibiting tumor growth. Taken together, our data support PRMT1 as a compelling target in PDAC and informs a mechanism-based translational strategy for future therapeutic development.Statement of significancePDAC is a highly lethal cancer with limited therapeutic options. This study identified and characterized PRMT1-dependent regulation of RNA metabolism and coordination of key cellular processes required for PDAC tumor growth, defining a mechanism-based translational hypothesis for PRMT1 inhibitors.

Published
2021

9. Clonal dominance defines metastatic dissemination in pancreatic cancer

Author

Ho, I-Lin, primary, Li, Chieh-Yuan, additional, Wang, Fuchenchu, additional, Zhao, Li, additional, Liu, Jingjing, additional, Yen, Er-Yen, additional, Dyke, Charles A., additional, Shah, Rutvi, additional, Liu, Zhaoliang, additional, Çetin, Ali Osman, additional, Chu, Yanshuo, additional, Citron, Francesca, additional, Attanasio, Sergio, additional, Corti, Denise, additional, Darbaniyan, Faezeh, additional, Del Poggetto, Edoardo, additional, Loponte, Sara, additional, Liu, Jintan, additional, Soeung, Melinda, additional, Chen, Ziheng, additional, Jiang, Shan, additional, Jiang, Hong, additional, Inoue, Akira, additional, Gao, Sisi, additional, Deem, Angela, additional, Feng, Ningping, additional, Ying, Haoqiang, additional, Kim, Michael, additional, Giuliani, Virginia, additional, Genovese, Giannicola, additional, Zhang, Jianhua, additional, Futreal, Andrew, additional, Maitra, Anirban, additional, Heffernan, Timothy, additional, Wang, Linghua, additional, Do, Kim-Anh, additional, Gargiulo, Gaetano, additional, Draetta, Giulio, additional, Carugo, Alessandro, additional, Lin, Ruitao, additional, and Viale, Andrea, additional

Published
2024
Full Text
View/download PDF

11. Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles

Author

Farshidfar, Farshad, Zheng, Siyuan, Gingras, Marie-Claude, Newton, Yulia, Shih, Juliann, Robertson, A Gordon, Hinoue, Toshinori, Hoadley, Katherine A, Gibb, Ewan A, Roszik, Jason, Covington, Kyle R, Wu, Chia-Chin, Shinbrot, Eve, Stransky, Nicolas, Hegde, Apurva, Yang, Ju Dong, Reznik, Ed, Sadeghi, Sara, Pedamallu, Chandra Sekhar, Ojesina, Akinyemi I, Hess, Julian M, Auman, J Todd, Rhie, Suhn K, Bowlby, Reanne, Borad, Mitesh J, Network, The Cancer Genome Atlas, Akbani, Rehan, Allotey, Loretta K, Ally, Adrian, Alvaro, Domenico, Andersen, Jesper B, Appelbaum, Elizabeth L, Arora, Arshi, Balasundaram, Miruna, Balu, Saianand, Bardeesy, Nabeel, Bathe, Oliver F, Baylin, Stephen B, Beroukhim, Rameen, Berrios, Mario, Bodenheimer, Tom, Boice, Lori, Bootwalla, Moiz S, Bowen, Jay, Bragazzi, Maria Consiglia, Brooks, Denise, Cardinale, Vincenzo, Carlsen, Rebecca, Carpino, Guido, Carvalho, Andre L, Chaiteerakij, Roongruedee, Chandan, Vishal C, Cherniack, Andrew D, Chin, Lynda, Cho, Juok, Choe, Gina, Chuah, Eric, Chudamani, Sudha, Cibulskis, Carrie, Cordes, Matthew G, Crain, Daniel, Curley, Erin, De Rose, Agostino Maria, Defreitas, Timothy, Demchok, John A, Deshpande, Vikram, Dhalla, Noreen, Ding, Li, Evason, Kimberley, Felau, Ina, Ferguson, Martin L, Foo, Wai Chin, Franchitto, Antonio, Frazer, Scott, Fronick, Catrina C, Fulton, Lucinda A, Fulton, Robert S, Gabriel, Stacey B, Gardner, Johanna, Gastier-Foster, Julie M, Gaudio, Eugenio, Gehlenborg, Nils, Genovese, Giannicola, Gerken, Mark, Getz, Gad, Giama, Nasra H, Gibbs, Richard A, Giuliante, Felice, Grazi, Gian Luca, Hayes, D Neil, Hegde, Apurva M, and Heiman, David I

Subjects
Liver Cancer, Digestive Diseases, Liver Disease, Biotechnology, Human Genome, Genetics, Cancer, Rare Diseases, Digestive Diseases - (Gallbladder), Adult, Aged, Aged, 80 and over, Bile Duct Neoplasms, Cholangiocarcinoma, Chromatin, DNA Methylation, DNA-Binding Proteins, Female, Gene Expression Regulation, Neoplastic, Genomics, Humans, Isocitrate Dehydrogenase, Liver, Liver Neoplasms, Male, Middle Aged, Mitochondria, Mutation, Nuclear Proteins, Pancreatic Neoplasms, Promoter Regions, Genetic, RNA, Long Noncoding, RNA, Messenger, Transcription Factors, Cancer Genome Atlas Network, ARID1A, DNA methylation, IDH, RNA sequencing, TCGA, cholangiocarcinoma, integrative genomics, lncRNAs, multi-omics, whole exome, Biochemistry and Cell Biology, Medical Physiology
Abstract

Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDH mutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the multi-platform data, we observed that ARID1A exhibited DNA hypermethylation and decreased expression in the IDH mutant subtype. More broadly, we found that IDH mutations are associated with an expanded histological spectrum of liver tumors with molecular features that stratify with CCA. Our studies reveal insights into the molecular pathogenesis and heterogeneity of cholangiocarcinoma and provide classification information of potential therapeutic significance.

Published
2017

12. Genomic deletion of malic enzyme 2 confers collateral lethality in pancreatic cancer

Author

Dey, Prasenjit, Baddour, Joelle, Muller, Florian, Wu, Chia Chin, Wang, Huamin, Liao, Wen-Ting, Lan, Zangdao, Chen, Alina, Gutschner, Tony, Kang, Yaan, Fleming, Jason, Satani, Nikunj, Zhao, Di, Achreja, Abhinav, Yang, Lifeng, Lee, Jiyoon, Chang, Edward, Genovese, Giannicola, Viale, Andrea, Ying, Haoqiang, Draetta, Giulio, Maitra, Anirban, Wang, Y Alan, Nagrath, Deepak, and DePinho, Ronald A

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Biological Sciences, Rare Diseases, Cancer, Pancreatic Cancer, Digestive Diseases, Biotechnology, Ovarian Cancer, Development of treatments and therapeutic interventions, Aetiology, 2.1 Biological and endogenous factors, 5.1 Pharmaceuticals, AMP-Activated Protein Kinases, Amino Acids, Branched-Chain, Animals, Biocatalysis, Carcinoma, Pancreatic Ductal, Gene Deletion, Humans, Ketoglutaric Acids, Malate Dehydrogenase, Male, Mice, Minor Histocompatibility Antigens, Mitochondria, NADP, Pancreatic Neoplasms, Pregnancy Proteins, Reactive Oxygen Species, Sterol Regulatory Element Binding Protein 1, Transaminases, General Science & Technology
Abstract

The genome of pancreatic ductal adenocarcinoma (PDAC) frequently contains deletions of tumour suppressor gene loci, most notably SMAD4, which is homozygously deleted in nearly one-third of cases. As loss of neighbouring housekeeping genes can confer collateral lethality, we sought to determine whether loss of the metabolic gene malic enzyme 2 (ME2) in the SMAD4 locus would create cancer-specific metabolic vulnerability upon targeting of its paralogous isoform ME3. The mitochondrial malic enzymes (ME2 and ME3) are oxidative decarboxylases that catalyse the conversion of malate to pyruvate and are essential for NADPH regeneration and reactive oxygen species homeostasis. Here we show that ME3 depletion selectively kills ME2-null PDAC cells in a manner consistent with an essential function for ME3 in ME2-null cancer cells. Mechanistically, integrated metabolomic and molecular investigation of cells deficient in mitochondrial malic enzymes revealed diminished NADPH production and consequent high levels of reactive oxygen species. These changes activate AMP activated protein kinase (AMPK), which in turn directly suppresses sterol regulatory element-binding protein 1 (SREBP1)-directed transcription of its direct targets including the BCAT2 branched-chain amino acid transaminase 2) gene. BCAT2 catalyses the transfer of the amino group from branched-chain amino acids to α-ketoglutarate (α-KG) thereby regenerating glutamate, which functions in part to support de novo nucleotide synthesis. Thus, mitochondrial malic enzyme deficiency, which results in impaired NADPH production, provides a prime 'collateral lethality' therapeutic strategy for the treatment of a substantial fraction of patients diagnosed with this intractable disease.

Published
2017

15. Abstract A011: DPY30 regulates immunoediting by suppressing uncoordinated DNA replication in pancreatic cancer

Author

Citron, Francesca, primary, Perelli, Luigi, additional, Balestrieri, Chiara, additional, Cecchetto, Luca, additional, Chu, Yanshuo, additional, Ho, I-Lin, additional, Zhang, Li, additional, Yen, Er-Yen, additional, Montanez, Luis Castillo, additional, Shah, Rutvi, additional, Attanasio, Sergio, additional, Srinivasan, Sanjana, additional, Dyke, Charles, additional, Chen, Ko-Chien, additional, Jiang, Shan, additional, Pan, Jing, additional, Gao, Sisi, additional, Wang, Huamin, additional, Yao, Wantong, additional, Wang, Linghua, additional, Pilato, Mauro Di, additional, Genovese, Giannicola, additional, Viale, Andrea, additional, and Draetta, Giulio, additional

Published
2024
Full Text
View/download PDF

16. The KRAS mutational spectrum and its clinical implications in pancreatic cancer.

Author

Perelli, Luigi, Genovese, Giannicola, and Draetta, Giulio F.

Subjects
*PANCREATIC duct, *DISEASE progression, *RAS oncogenes, *PANCREATIC cancer, *CANCER cells
Abstract

In this issue of Cancer Cell , McIntyre et al. show that specific mutations in the KRAS proto-oncogene shape clinical progression of pancreatic ductal adenocarcinoma (PDAC). Importantly, they find that the KRAS G12R mutation is enriched in early-stage PDAC, and it is characterized by distinctly activated molecular programs. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

17. Integrative molecular characterization of sarcomatoid and rhabdoid renal cell carcinoma

Author

Bakouny, Ziad, Braun, David A., Shukla, Sachet A., Pan, Wenting, Gao, Xin, Hou, Yue, Flaifel, Abdallah, Tang, Stephen, Bosma-Moody, Alice, He, Meng Xiao, Vokes, Natalie, Nyman, Jackson, Xie, Wanling, Nassar, Amin H., Abou Alaiwi, Sarah, Flippot, Ronan, Bouchard, Gabrielle, Steinharter, John A., Nuzzo, Pier Vitale, Ficial, Miriam, Sant’Angelo, Miriam, Forman, Juliet, Berchuck, Jacob E., Dudani, Shaan, Bi, Kevin, Park, Jihye, Camp, Sabrina, Sticco-Ivins, Maura, Hirsch, Laure, Baca, Sylvan C., Wind-Rotolo, Megan, Ross-Macdonald, Petra, Sun, Maxine, Lee, Gwo-Shu Mary, Chang, Steven L., Wei, Xiao X., McGregor, Bradley A., Harshman, Lauren C., Genovese, Giannicola, Ellis, Leigh, Pomerantz, Mark, Hirsch, Michelle S., Freedman, Matthew L., Atkins, Michael B., Wu, Catherine J., Ho, Thai H., Linehan, W. Marston, McDermott, David F., Heng, Daniel Y. C., Viswanathan, Srinivas R., Signoretti, Sabina, Van Allen, Eliezer M., and Choueiri, Toni K.

Published
2021
Full Text
View/download PDF

18. Genomic Classification of Cutaneous Melanoma

Author

Network, The Cancer Genome Atlas, Akbani, Rehan, Akdemir, Kadir C, Aksoy, B Arman, Albert, Monique, Ally, Adrian, Amin, Samirkumar B, Arachchi, Harindra, Arora, Arshi, Auman, J Todd, Ayala, Brenda, Baboud, Julien, Balasundaram, Miruna, Balu, Saianand, Barnabas, Nandita, Bartlett, John, Bartlett, Pam, Bastian, Boris C, Baylin, Stephen B, Behera, Madhusmita, Belyaev, Dmitry, Benz, Christopher, Bernard, Brady, Beroukhim, Rameen, Bir, Natalie, Black, Aaron D, Bodenheimer, Tom, Boice, Lori, Boland, Genevieve M, Bono, Riccardo, Bootwalla, Moiz S, Bosenberg, Marcus, Bowen, Jay, Bowlby, Reanne, Bristow, Christopher A, Brockway-Lunardi, Laura, Brooks, Denise, Brzezinski, Jakub, Bshara, Wiam, Buda, Elizabeth, Burns, William R, Butterfield, Yaron SN, Button, Michael, Calderone, Tiffany, Cappellini, Giancarlo Antonini, Carter, Candace, Carter, Scott L, Cherney, Lynn, Cherniack, Andrew D, Chevalier, Aaron, Chin, Lynda, Cho, Juok, Cho, Raymond J, Choi, Yoon-La, Chu, Andy, Chudamani, Sudha, Cibulskis, Kristian, Ciriello, Giovanni, Clarke, Amanda, Coons, Stephen, Cope, Leslie, Crain, Daniel, Curley, Erin, Danilova, Ludmila, D’Atri, Stefania, Davidsen, Tanja, Davies, Michael A, Delman, Keith A, Demchok, John A, Deng, Qixia A, Deribe, Yonathan Lissanu, Dhalla, Noreen, Dhir, Rajiv, DiCara, Daniel, Dinikin, Michael, Dubina, Michael, Ebrom, J Stephen, Egea, Sophie, Eley, Greg, Engel, Jay, Eschbacher, Jennifer M, Fedosenko, Konstantin V, Felau, Ina, Fennell, Timothy, Ferguson, Martin L, Fisher, Sheila, Flaherty, Keith T, Frazer, Scott, Frick, Jessica, Fulidou, Victoria, Gabriel, Stacey B, Gao, Jianjiong, Gardner, Johanna, Garraway, Levi A, Gastier-Foster, Julie M, Gaudioso, Carmelo, Gehlenborg, Nils, Genovese, Giannicola, Gerken, Mark, and Gershenwald, Jeffrey E

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Biomedical and Clinical Sciences, Immunology, Oncology and Carcinogenesis, Biotechnology, Human Genome, Genetics, Cancer, Precision Medicine, Cancer Genomics, Databases, Genetic, Humans, Melanoma, Mutation, National Cancer Institute (U.S.), Skin Neoplasms, United States, Cancer Genome Atlas Network, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

We describe the landscape of genomic alterations in cutaneous melanomas through DNA, RNA, and protein-based analysis of 333 primary and/or metastatic melanomas from 331 patients. We establish a framework for genomic classification into one of four subtypes based on the pattern of the most prevalent significantly mutated genes: mutant BRAF, mutant RAS, mutant NF1, and Triple-WT (wild-type). Integrative analysis reveals enrichment of KIT mutations and focal amplifications and complex structural rearrangements as a feature of the Triple-WT subtype. We found no significant outcome correlation with genomic classification, but samples assigned a transcriptomic subclass enriched for immune gene expression associated with lymphocyte infiltrate on pathology review and high LCK protein expression, a T cell marker, were associated with improved patient survival. This clinicopathological and multi-dimensional analysis suggests that the prognosis of melanoma patients with regional metastases is influenced by tumor stroma immunobiology, offering insights to further personalize therapeutic decision-making.

Published
2015

19. Evolutionary fingerprints of EMT in pancreatic cancers

Author

Perelli, Luigi, primary, Zhang, Li, additional, Mangiameli, Sarah, additional, Russell, Andrew James Charles, additional, Giannese, Francesca, additional, Peng, Fuduan, additional, Carbone, Federica, additional, Le, Courtney, additional, Khan, Hania, additional, Citron, Francesca, additional, Soeung, Melinda, additional, Lam, Truong, additional, Lundgren, Sebastian, additional, Zhu, Cihui, additional, Catania, Desiree, additional, Feng, Ningping, additional, Gurreri, Enrico, additional, Sgambato, Alessandro, additional, Tortora, Giampaolo, additional, Draetta, Giulio, additional, Tonon, Giovanni, additional, Futreal, Andrew, additional, Giuliani, Virginia, additional, Carugo, Alessandro, additional, Viale, Andrea, additional, Heffernan, Timothy, additional, Wang, Linghua, additional, Cittaro, Davide, additional, Chen, Fei, additional, and Genovese, Giannicola, additional

Published
2023
Full Text
View/download PDF

20. The Somatic Genomic Landscape of Glioblastoma

Author

Brennan, Cameron W, Verhaak, Roel GW, McKenna, Aaron, Campos, Benito, Noushmehr, Houtan, Salama, Sofie R, Zheng, Siyuan, Chakravarty, Debyani, Sanborn, J Zachary, Berman, Samuel H, Beroukhim, Rameen, Bernard, Brady, Wu, Chang-Jiun, Genovese, Giannicola, Shmulevich, Ilya, Barnholtz-Sloan, Jill, Zou, Lihua, Vegesna, Rahulsimham, Shukla, Sachet A, Ciriello, Giovanni, Yung, WK, Zhang, Wei, Sougnez, Carrie, Mikkelsen, Tom, Aldape, Kenneth, Bigner, Darell D, Van Meir, Erwin G, Prados, Michael, Sloan, Andrew, Black, Keith L, Eschbacher, Jennifer, Finocchiaro, Gaetano, Friedman, William, Andrews, David W, Guha, Abhijit, Iacocca, Mary, O’Neill, Brian P, Foltz, Greg, Myers, Jerome, Weisenberger, Daniel J, Penny, Robert, Kucherlapati, Raju, Perou, Charles M, Hayes, D Neil, Gibbs, Richard, Marra, Marco, Mills, Gordon B, Lander, Eric, Spellman, Paul, Wilson, Richard, Sander, Chris, Weinstein, John, Meyerson, Matthew, Gabriel, Stacey, Laird, Peter W, Haussler, David, Getz, Gad, Chin, Lynda, Network, TCGA Research, Benz, Christopher, Barrett, Wendi, Ostrom, Quinn, Wolinsky, Yingli, Bose, Bikash, Boulos, Paul T, Boulos, Madgy, Brown, Jenn, Czerinski, Christine, Eppley, Matthew, Kempista, Thelma, Kitko, Teresa, Koyfman, Yakov, Rabeno, Brenda, Rastogi, Pawan, Sugarman, Michael, Swanson, Patricia, Yalamanchii, Kennedy, Otey, Ilana P, Liu, Yingchun Spring, Xiao, Yonghong, Auman, J Todd, Chen, Peng-Chieh, Hadjipanayis, Angela, Lee, Eunjung, Lee, Semin, Park, Peter J, Seidman, Jonathan, Yang, Lixing, Kalkanis, Steven, Poisson, Laila M, Raghunathan, Aditya, Scarpace, Lisa, Bressler, Ryan, and Eakin, Andrea

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Genetics, Brain Cancer, Cancer, Brain Disorders, Rare Diseases, Cancer Genomics, Precision Medicine, Orphan Drug, Neurosciences, Human Genome, Biotechnology, 2.1 Biological and endogenous factors, 4.1 Discovery and preclinical testing of markers and technologies, 5.1 Pharmaceuticals, 4.2 Evaluation of markers and technologies, Brain Neoplasms, Female, Gene Expression Profiling, Gene Regulatory Networks, Glioblastoma, Humans, Male, Mutation, Proteome, Signal Transduction, TCGA Research Network, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

We describe the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer.

Published
2013

22. SMARCB1 regulates the hypoxic stress response in sickle cell trait

Author

Soeung, Melinda, primary, Perelli, Luigi, additional, Chen, Ziheng, additional, Dondossola, Eleonora, additional, Ho, I-Lin, additional, Carbone, Federica, additional, Zhang, Li, additional, Khan, Hania, additional, Le, Courtney N., additional, Zhu, Cihui, additional, Peoples, Michael D., additional, Feng, Ningping, additional, Jiang, Shan, additional, Zacharias, Niki Millward, additional, Minelli, Rosalba, additional, Shapiro, Daniel D., additional, Deem, Angela K., additional, Gao, Sisi, additional, Cheng, Emily H., additional, Lucchetti, Donatella, additional, Walker, Cheryl L., additional, Carugo, Alessandro, additional, Giuliani, Virginia, additional, Heffernan, Timothy P., additional, Viale, Andrea, additional, Tannir, Nizar M., additional, Draetta, Giulio F., additional, Msaouel, Pavlos, additional, and Genovese, Giannicola, additional

Published
2023
Full Text
View/download PDF

24. Neddylation inhibition sensitises renal medullary carcinoma tumours to platinum chemotherapy

Author

Shapiro, Daniel D., primary, Zacharias, Niki Millward, additional, Tripathi, Durga N., additional, Karki, Menuka, additional, Bertocchio, Jean‐Philippe, additional, Soeung, Melinda, additional, He, Rong, additional, Westerman, Mary E., additional, Gao, Jianjun, additional, Rao, Priya, additional, Lam, Truong N. A., additional, Jonasch, Eric, additional, Perelli, Luigi, additional, Cheng, Emily H., additional, Carugo, Alessandro, additional, Heffernan, Timothy P., additional, Walker, Cheryl L., additional, Genovese, Giannicola, additional, Tannir, Nizar M., additional, Karam, Jose A., additional, and Msaouel, Pavlos, additional

Published
2023
Full Text
View/download PDF

25. Abstract 77: Recapitulating metastatic colorectal cancer in somatic mutation models for investigating the tumor immune microenvironment in minimal residual disease

Author

Mohamed, Alaa M., primary, Soeung, Melinda, additional, Alshenaifi, Jumanah, additional, Fowlkes, Natalie, additional, Manyam, Ganiraju, additional, Davis, Jennifer, additional, Anderson, Amanda, additional, Norton, Will, additional, Deem, Angela K., additional, Gao, Sisi, additional, Khanduri, Isha, additional, Bistow, Christopher, additional, Carbone, Federica, additional, Napolitano, Stefania, additional, Huang, Justin, additional, Maru, Dipen M., additional, Menter, David G., additional, Draetta, Giulio F., additional, Genovese, Giannicola, additional, and Kopetz, Scott, additional

Published
2023
Full Text
View/download PDF

26. Abstract 94: Advanced preclinical modeling reveals unique monosomy 3 associated biology in late-stage uveal melanoma

Author

Rose, Johnathon L., primary, Srinivasan, Sanjana, additional, He, Meng, additional, Minelli, Rosalba, additional, Liu, Chiu-Yi, additional, Gay, Jason, additional, Daniele, Joseph R., additional, Peoples, Michael, additional, Soeung, Melinda, additional, Ramamoorthy, Vandhana, additional, Lopez, Anastasia, additional, Deckard, Charles, additional, Meyers, Brooke, additional, Poggetto, Edoardo Del, additional, Zamler, Daniel, additional, Huang, Justin, additional, Perelli, Luigi, additional, Wani, Khalida, additional, Bristow, Christopher, additional, Feng, Ningping, additional, Vellano, Christopher P., additional, Marszalek, Joe, additional, Lazar, Alexander J., additional, Futreal, Andrew, additional, Draetta, Giulio F., additional, Woodman, Scott E., additional, Heffernan, Timothy, additional, Genovese, Giannicola, additional, Carugo, Alessandro, additional, and Giuliani, Virginia, additional

Published
2023
Full Text
View/download PDF

27. Abstract 303: DPY30 loss leads to DNA re-replication and immunoediting in pancreatic ductal adenocarcinoma

Author

Citron, Francesca, primary, Perelli, Luigi, additional, Chu, Yanshuo, additional, Srinivasan, Sanjana, additional, Ho, I-Lin, additional, Yen, Er-Yen, additional, Shah, Rutvi, additional, Attanasio, Sergio, additional, Montanez, Luis Castillo, additional, Pilato, Mauro Di, additional, Jiang, Shan, additional, Yao, Wantong, additional, Gao, Sisi, additional, Deem, Angela, additional, Genovese, Giannicola, additional, Wang, Linghua, additional, Giuliani, Virginia, additional, Viale, Andrea, additional, and Draetta, Giulio F., additional

Published
2023
Full Text
View/download PDF

28. Abstract 92: Deploying spatial transcriptomics to inform intratumoral heterogeneity in late-stage uveal melanoma leveraging advanced preclinical modeling and clinical samples

Author

Srinivasan, Sanjana, primary, Rose, Johnathon, additional, Daniele, Joseph R., additional, Peoples, Michael, additional, He, Meng, additional, Minelli, Rosalba, additional, Liu, Chiu-Yi, additional, Gay, Jason, additional, Soeung, Melinda, additional, Wani, Khalida, additional, Perelli, Luigi, additional, Loza, Dmitriy, additional, Feng, Ningping, additional, Vellano, Christopher P., additional, Marszalek, Joseph, additional, Draetta, Giulio F., additional, Futreal, P. Andrew, additional, Woodman, Scott E., additional, Lazar, Alexander J., additional, Heffernan, Timothy, additional, Carugo, Alessandro, additional, Genovese, Giannicola, additional, and Giuliani, Virginia, additional

Published
2023
Full Text
View/download PDF

29. Abstract 5788: Single-cell and spatial transcriptomic mapping of human renal cell carcinoma brain metastases uncovers actionable immune-resistance targets

Author

Hasanov, Elshad, primary, Lam, Truong Nguyen Anh, additional, Lin, Jerome, additional, Reville, Patrick K., additional, Hasanov, Merve, additional, Casasent, Anna K., additional, Shih, David, additional, Hanalioglu, Sahin, additional, Bilen, Mehmet Asim, additional, Alhalabi, Omar, additional, Babaoglu, Berrin, additional, Baylarov, Baylar, additional, Osunkoya, Adeboye O., additional, Norberg, Lisa M., additional, Gumin, Joy, additional, Tran, Tuan M., additional, Li, Jianzhuo, additional, Hoang, Anh G., additional, Chancoco, Haidee D., additional, Kerrigan, Brittany C. Parker, additional, Thompson, Erika J., additional, Kim, Betty YS, additional, Suki, Dima, additional, Mut, Melike, additional, Soylemezoglu, Figen, additional, Genovese, Giannicola, additional, Akdemir, Kadir C., additional, Tawbi, Hussain A., additional, Tannir, Nizar M., additional, McAllister, Florencia, additional, Davies, Michael A., additional, Sharma, Padmanee, additional, Huse, Jason, additional, Lang, Frederick, additional, Navin, Nicholas, additional, and Jonasch, Eric, additional

Published
2023
Full Text
View/download PDF

30. Data from microRNA Regulatory Network Inference Identifies miR-34a as a Novel Regulator of TGF-β Signaling in Glioblastoma

Author

Genovese, Giannicola, primary, Ergun, Ayla, primary, Shukla, Sachet A., primary, Campos, Benito, primary, Hanna, Jason, primary, Ghosh, Papia, primary, Quayle, Steven N., primary, Rai, Kunal, primary, Colla, Simona, primary, Ying, Haoqiang, primary, Wu, Chang-Jiun, primary, Sarkar, Sharmistha, primary, Xiao, Yonghong, primary, Zhang, Jianhua, primary, Zhang, Hailei, primary, Kwong, Lawrence, primary, Dunn, Katherine, primary, Wiedemeyer, Wolf Ruprecht, primary, Brennan, Cameron, primary, Zheng, Hongwu, primary, Rimm, David L., primary, Collins, James J., primary, and Chin, Lynda, primary

Published
2023
Full Text
View/download PDF

31. Supplementary Tables 1-10 from microRNA Regulatory Network Inference Identifies miR-34a as a Novel Regulator of TGF-β Signaling in Glioblastoma

Author

Genovese, Giannicola, primary, Ergun, Ayla, primary, Shukla, Sachet A., primary, Campos, Benito, primary, Hanna, Jason, primary, Ghosh, Papia, primary, Quayle, Steven N., primary, Rai, Kunal, primary, Colla, Simona, primary, Ying, Haoqiang, primary, Wu, Chang-Jiun, primary, Sarkar, Sharmistha, primary, Xiao, Yonghong, primary, Zhang, Jianhua, primary, Zhang, Hailei, primary, Kwong, Lawrence, primary, Dunn, Katherine, primary, Wiedemeyer, Wolf Ruprecht, primary, Brennan, Cameron, primary, Zheng, Hongwu, primary, Rimm, David L., primary, Collins, James J., primary, and Chin, Lynda, primary

Published
2023
Full Text
View/download PDF

32. Data from Oncogenic KRAS-Driven Metabolic Reprogramming in Pancreatic Cancer Cells Utilizes Cytokines from the Tumor Microenvironment

Author

Dey, Prasenjit, primary, Li, Jun, primary, Zhang, Jianhua, primary, Chaurasiya, Surendra, primary, Strom, Anders, primary, Wang, Huamin, primary, Liao, Wen-Ting, primary, Cavallaro, Frederick, primary, Denz, Parker, primary, Bernard, Vincent, primary, Yen, Er-Yen, primary, Genovese, Giannicola, primary, Gulhati, Pat, primary, Liu, Jielin, primary, Chakravarti, Deepavali, primary, Deng, Pingna, primary, Zhang, Tingxin, primary, Carbone, Federica, primary, Chang, Qing, primary, Ying, Haoqiang, primary, Shang, Xiaoying, primary, Spring, Denise J., primary, Ghosh, Bidyut, primary, Putluri, Nagireddy, primary, Maitra, Anirban, primary, Wang, Y. Alan, primary, and DePinho, Ronald A., primary

Published
2023
Full Text
View/download PDF

33. Data from Medium-Chain Acyl-CoA Dehydrogenase Protects Mitochondria from Lipid Peroxidation in Glioblastoma

Author

Puca, Francesca, primary, Yu, Fei, primary, Bartolacci, Caterina, primary, Pettazzoni, Piergiorgio, primary, Carugo, Alessandro, primary, Huang-Hobbs, Emmet, primary, Liu, Jintan, primary, Zanca, Ciro, primary, Carbone, Federica, primary, Del Poggetto, Edoardo, primary, Gumin, Joy, primary, Dasgupta, Pushan, primary, Seth, Sahil, primary, Srinivasan, Sanjana, primary, Lang, Frederick F., primary, Sulman, Erik P., primary, Lorenzi, Philip L., primary, Tan, Lin, primary, Shan, Mengrou, primary, Tolstyka, Zachary P., primary, Kachman, Maureen, primary, Zhang, Li, primary, Gao, Sisi, primary, Deem, Angela K., primary, Genovese, Giannicola, primary, Scaglioni, Pier Paolo, primary, Lyssiotis, Costas A., primary, Viale, Andrea, primary, and Draetta, Giulio F., primary

Published
2023
Full Text
View/download PDF

34. Supplementary Figures 1-13 from microRNA Regulatory Network Inference Identifies miR-34a as a Novel Regulator of TGF-β Signaling in Glioblastoma

Author

Genovese, Giannicola, primary, Ergun, Ayla, primary, Shukla, Sachet A., primary, Campos, Benito, primary, Hanna, Jason, primary, Ghosh, Papia, primary, Quayle, Steven N., primary, Rai, Kunal, primary, Colla, Simona, primary, Ying, Haoqiang, primary, Wu, Chang-Jiun, primary, Sarkar, Sharmistha, primary, Xiao, Yonghong, primary, Zhang, Jianhua, primary, Zhang, Hailei, primary, Kwong, Lawrence, primary, Dunn, Katherine, primary, Wiedemeyer, Wolf Ruprecht, primary, Brennan, Cameron, primary, Zheng, Hongwu, primary, Rimm, David L., primary, Collins, James J., primary, and Chin, Lynda, primary

Published
2023
Full Text
View/download PDF

35. Supplementary Figures from Medium-Chain Acyl-CoA Dehydrogenase Protects Mitochondria from Lipid Peroxidation in Glioblastoma

Author

Puca, Francesca, primary, Yu, Fei, primary, Bartolacci, Caterina, primary, Pettazzoni, Piergiorgio, primary, Carugo, Alessandro, primary, Huang-Hobbs, Emmet, primary, Liu, Jintan, primary, Zanca, Ciro, primary, Carbone, Federica, primary, Del Poggetto, Edoardo, primary, Gumin, Joy, primary, Dasgupta, Pushan, primary, Seth, Sahil, primary, Srinivasan, Sanjana, primary, Lang, Frederick F., primary, Sulman, Erik P., primary, Lorenzi, Philip L., primary, Tan, Lin, primary, Shan, Mengrou, primary, Tolstyka, Zachary P., primary, Kachman, Maureen, primary, Zhang, Li, primary, Gao, Sisi, primary, Deem, Angela K., primary, Genovese, Giannicola, primary, Scaglioni, Pier Paolo, primary, Lyssiotis, Costas A., primary, Viale, Andrea, primary, and Draetta, Giulio F., primary

Published
2023
Full Text
View/download PDF

36. Supplementary Methods, Figure Legends 1-13, Table Legends 1-10 from microRNA Regulatory Network Inference Identifies miR-34a as a Novel Regulator of TGF-β Signaling in Glioblastoma

Author

Genovese, Giannicola, primary, Ergun, Ayla, primary, Shukla, Sachet A., primary, Campos, Benito, primary, Hanna, Jason, primary, Ghosh, Papia, primary, Quayle, Steven N., primary, Rai, Kunal, primary, Colla, Simona, primary, Ying, Haoqiang, primary, Wu, Chang-Jiun, primary, Sarkar, Sharmistha, primary, Xiao, Yonghong, primary, Zhang, Jianhua, primary, Zhang, Hailei, primary, Kwong, Lawrence, primary, Dunn, Katherine, primary, Wiedemeyer, Wolf Ruprecht, primary, Brennan, Cameron, primary, Zheng, Hongwu, primary, Rimm, David L., primary, Collins, James J., primary, and Chin, Lynda, primary

Published
2023
Full Text
View/download PDF

37. Supplementary Data from Oncogenic KRAS-Driven Metabolic Reprogramming in Pancreatic Cancer Cells Utilizes Cytokines from the Tumor Microenvironment

Author

Dey, Prasenjit, primary, Li, Jun, primary, Zhang, Jianhua, primary, Chaurasiya, Surendra, primary, Strom, Anders, primary, Wang, Huamin, primary, Liao, Wen-Ting, primary, Cavallaro, Frederick, primary, Denz, Parker, primary, Bernard, Vincent, primary, Yen, Er-Yen, primary, Genovese, Giannicola, primary, Gulhati, Pat, primary, Liu, Jielin, primary, Chakravarti, Deepavali, primary, Deng, Pingna, primary, Zhang, Tingxin, primary, Carbone, Federica, primary, Chang, Qing, primary, Ying, Haoqiang, primary, Shang, Xiaoying, primary, Spring, Denise J., primary, Ghosh, Bidyut, primary, Putluri, Nagireddy, primary, Maitra, Anirban, primary, Wang, Y. Alan, primary, and DePinho, Ronald A., primary

Published
2023
Full Text
View/download PDF

38. Supplementary Table 1 from Loss of ARID1A Promotes Epithelial–Mesenchymal Transition and Sensitizes Pancreatic Tumors to Proteotoxic Stress

Author

Tomihara, Hideo, primary, Carbone, Federica, primary, Perelli, Luigi, primary, Huang, Justin K., primary, Soeung, Melinda, primary, Rose, Johnathon L., primary, Robinson, Frederick S., primary, Lissanu Deribe, Yonathan, primary, Feng, Ningping, primary, Takeda, Mitsunobu, primary, Inoue, Akira, primary, Poggetto, Edoardo Del, primary, Deem, Angela K., primary, Maitra, Anirban, primary, Msaouel, Pavlos, primary, Tannir, Nizar M., primary, Draetta, Giulio F., primary, Viale, Andrea, primary, Heffernan, Timothy P., primary, Bristow, Christopher A., primary, Carugo, Alessandro, primary, and Genovese, Giannicola, primary

Published
2023
Full Text
View/download PDF

39. Supplementary Figure 2 from Loss of ARID1A Promotes Epithelial–Mesenchymal Transition and Sensitizes Pancreatic Tumors to Proteotoxic Stress

Author

Tomihara, Hideo, primary, Carbone, Federica, primary, Perelli, Luigi, primary, Huang, Justin K., primary, Soeung, Melinda, primary, Rose, Johnathon L., primary, Robinson, Frederick S., primary, Lissanu Deribe, Yonathan, primary, Feng, Ningping, primary, Takeda, Mitsunobu, primary, Inoue, Akira, primary, Poggetto, Edoardo Del, primary, Deem, Angela K., primary, Maitra, Anirban, primary, Msaouel, Pavlos, primary, Tannir, Nizar M., primary, Draetta, Giulio F., primary, Viale, Andrea, primary, Heffernan, Timothy P., primary, Bristow, Christopher A., primary, Carugo, Alessandro, primary, and Genovese, Giannicola, primary

Published
2023
Full Text
View/download PDF

40. Supplementary Figure 3 from Loss of ARID1A Promotes Epithelial–Mesenchymal Transition and Sensitizes Pancreatic Tumors to Proteotoxic Stress

Author

Tomihara, Hideo, primary, Carbone, Federica, primary, Perelli, Luigi, primary, Huang, Justin K., primary, Soeung, Melinda, primary, Rose, Johnathon L., primary, Robinson, Frederick S., primary, Lissanu Deribe, Yonathan, primary, Feng, Ningping, primary, Takeda, Mitsunobu, primary, Inoue, Akira, primary, Poggetto, Edoardo Del, primary, Deem, Angela K., primary, Maitra, Anirban, primary, Msaouel, Pavlos, primary, Tannir, Nizar M., primary, Draetta, Giulio F., primary, Viale, Andrea, primary, Heffernan, Timothy P., primary, Bristow, Christopher A., primary, Carugo, Alessandro, primary, and Genovese, Giannicola, primary

Published
2023
Full Text
View/download PDF

41. Supplementary Figure 1 from Loss of ARID1A Promotes Epithelial–Mesenchymal Transition and Sensitizes Pancreatic Tumors to Proteotoxic Stress

Author

Tomihara, Hideo, primary, Carbone, Federica, primary, Perelli, Luigi, primary, Huang, Justin K., primary, Soeung, Melinda, primary, Rose, Johnathon L., primary, Robinson, Frederick S., primary, Lissanu Deribe, Yonathan, primary, Feng, Ningping, primary, Takeda, Mitsunobu, primary, Inoue, Akira, primary, Poggetto, Edoardo Del, primary, Deem, Angela K., primary, Maitra, Anirban, primary, Msaouel, Pavlos, primary, Tannir, Nizar M., primary, Draetta, Giulio F., primary, Viale, Andrea, primary, Heffernan, Timothy P., primary, Bristow, Christopher A., primary, Carugo, Alessandro, primary, and Genovese, Giannicola, primary

Published
2023
Full Text
View/download PDF

42. Supplementary Legends from Loss of ARID1A Promotes Epithelial–Mesenchymal Transition and Sensitizes Pancreatic Tumors to Proteotoxic Stress

Author

Tomihara, Hideo, primary, Carbone, Federica, primary, Perelli, Luigi, primary, Huang, Justin K., primary, Soeung, Melinda, primary, Rose, Johnathon L., primary, Robinson, Frederick S., primary, Lissanu Deribe, Yonathan, primary, Feng, Ningping, primary, Takeda, Mitsunobu, primary, Inoue, Akira, primary, Poggetto, Edoardo Del, primary, Deem, Angela K., primary, Maitra, Anirban, primary, Msaouel, Pavlos, primary, Tannir, Nizar M., primary, Draetta, Giulio F., primary, Viale, Andrea, primary, Heffernan, Timothy P., primary, Bristow, Christopher A., primary, Carugo, Alessandro, primary, and Genovese, Giannicola, primary

Published
2023
Full Text
View/download PDF

43. Supplementary Table 2 from Loss of ARID1A Promotes Epithelial–Mesenchymal Transition and Sensitizes Pancreatic Tumors to Proteotoxic Stress

Author

Tomihara, Hideo, primary, Carbone, Federica, primary, Perelli, Luigi, primary, Huang, Justin K., primary, Soeung, Melinda, primary, Rose, Johnathon L., primary, Robinson, Frederick S., primary, Lissanu Deribe, Yonathan, primary, Feng, Ningping, primary, Takeda, Mitsunobu, primary, Inoue, Akira, primary, Poggetto, Edoardo Del, primary, Deem, Angela K., primary, Maitra, Anirban, primary, Msaouel, Pavlos, primary, Tannir, Nizar M., primary, Draetta, Giulio F., primary, Viale, Andrea, primary, Heffernan, Timothy P., primary, Bristow, Christopher A., primary, Carugo, Alessandro, primary, and Genovese, Giannicola, primary

Published
2023
Full Text
View/download PDF

44. Data Supplement from The RAC1 P29S Hotspot Mutation in Melanoma Confers Resistance to Pharmacological Inhibition of RAF

Author

Watson, Ian R., primary, Li, Liren, primary, Cabeceiras, Peter K., primary, Mahdavi, Mozhdeh, primary, Gutschner, Tony, primary, Genovese, Giannicola, primary, Wang, Guocan, primary, Fang, Zhuangna, primary, Tepper, James M., primary, Stemke-Hale, Katherine, primary, Tsai, Kenneth Y., primary, Davies, Michael A., primary, Mills, Gordon B., primary, and Chin, Lynda, primary

Published
2023
Full Text
View/download PDF

45. Data from Genetic Events That Limit the Efficacy of MEK and RTK Inhibitor Therapies in a Mouse Model of KRAS-Driven Pancreatic Cancer

Author

Pettazzoni, Piergiorgio, primary, Viale, Andrea, primary, Shah, Parantu, primary, Carugo, Alessandro, primary, Ying, Haoqiang, primary, Wang, Huamin, primary, Genovese, Giannicola, primary, Seth, Sahil, primary, Minelli, Rosalba, primary, Green, Tessa, primary, Huang-Hobbs, Emmet, primary, Corti, Denise, primary, Sanchez, Nora, primary, Nezi, Luigi, primary, Marchesini, Matteo, primary, Kapoor, Avnish, primary, Yao, Wantong, primary, Francesco, Maria E. Di, primary, Petrocchi, Alessia, primary, Deem, Angela K., primary, Scott, Kenneth, primary, Colla, Simona, primary, Mills, Gordon B., primary, Fleming, Jason B., primary, Heffernan, Timothy P., primary, Jones, Philip, primary, Toniatti, Carlo, primary, DePinho, Ronald A., primary, and Draetta, Giulio F., primary

Published
2023
Full Text
View/download PDF

46. Data from The RAC1 P29S Hotspot Mutation in Melanoma Confers Resistance to Pharmacological Inhibition of RAF

Author

Watson, Ian R., primary, Li, Liren, primary, Cabeceiras, Peter K., primary, Mahdavi, Mozhdeh, primary, Gutschner, Tony, primary, Genovese, Giannicola, primary, Wang, Guocan, primary, Fang, Zhuangna, primary, Tepper, James M., primary, Stemke-Hale, Katherine, primary, Tsai, Kenneth Y., primary, Davies, Michael A., primary, Mills, Gordon B., primary, and Chin, Lynda, primary

Published
2023
Full Text
View/download PDF

47. supplementary material and method from Genetic Events That Limit the Efficacy of MEK and RTK Inhibitor Therapies in a Mouse Model of KRAS-Driven Pancreatic Cancer

Author

Pettazzoni, Piergiorgio, primary, Viale, Andrea, primary, Shah, Parantu, primary, Carugo, Alessandro, primary, Ying, Haoqiang, primary, Wang, Huamin, primary, Genovese, Giannicola, primary, Seth, Sahil, primary, Minelli, Rosalba, primary, Green, Tessa, primary, Huang-Hobbs, Emmet, primary, Corti, Denise, primary, Sanchez, Nora, primary, Nezi, Luigi, primary, Marchesini, Matteo, primary, Kapoor, Avnish, primary, Yao, Wantong, primary, Francesco, Maria E. Di, primary, Petrocchi, Alessia, primary, Deem, Angela K., primary, Scott, Kenneth, primary, Colla, Simona, primary, Mills, Gordon B., primary, Fleming, Jason B., primary, Heffernan, Timothy P., primary, Jones, Philip, primary, Toniatti, Carlo, primary, DePinho, Ronald A., primary, and Draetta, Giulio F., primary

Published
2023
Full Text
View/download PDF

48. supplementary Figures S1-S10 from Genetic Events That Limit the Efficacy of MEK and RTK Inhibitor Therapies in a Mouse Model of KRAS-Driven Pancreatic Cancer

Author

Pettazzoni, Piergiorgio, primary, Viale, Andrea, primary, Shah, Parantu, primary, Carugo, Alessandro, primary, Ying, Haoqiang, primary, Wang, Huamin, primary, Genovese, Giannicola, primary, Seth, Sahil, primary, Minelli, Rosalba, primary, Green, Tessa, primary, Huang-Hobbs, Emmet, primary, Corti, Denise, primary, Sanchez, Nora, primary, Nezi, Luigi, primary, Marchesini, Matteo, primary, Kapoor, Avnish, primary, Yao, Wantong, primary, Francesco, Maria E. Di, primary, Petrocchi, Alessia, primary, Deem, Angela K., primary, Scott, Kenneth, primary, Colla, Simona, primary, Mills, Gordon B., primary, Fleming, Jason B., primary, Heffernan, Timothy P., primary, Jones, Philip, primary, Toniatti, Carlo, primary, DePinho, Ronald A., primary, and Draetta, Giulio F., primary

Published
2023
Full Text
View/download PDF

50. SMARCB1 regulates the hypoxic stress response in sickle cell trait

Author

Soeung, Melinda, Perelli, Luigi, Chen, Ziheng, Dondossola, Eleonora, Ho, I-Lin, Carbone, Federica, Zhang, Li, Khan, Hania, Le, Courtney N, Zhu, Cihui, Peoples, Michael D, Feng, Ningping, Jiang, Shan, Zacharias, Niki Millward, Minelli, Rosalba, Shapiro, Daniel D, Deem, Angela K, Gao, Sisi, Cheng, Emily H, Lucchetti, Donatella, Walker, Cheryl L, Carugo, Alessandro, Giuliani, Virginia, Heffernan, Timothy P, Viale, Andrea, Tannir, Nizar M, Draetta, Giulio F, Msaouel, Pavlo, Genovese, Giannicola, Lucchetti, Donatella (ORCID:0000-0001-8147-0079), Soeung, Melinda, Perelli, Luigi, Chen, Ziheng, Dondossola, Eleonora, Ho, I-Lin, Carbone, Federica, Zhang, Li, Khan, Hania, Le, Courtney N, Zhu, Cihui, Peoples, Michael D, Feng, Ningping, Jiang, Shan, Zacharias, Niki Millward, Minelli, Rosalba, Shapiro, Daniel D, Deem, Angela K, Gao, Sisi, Cheng, Emily H, Lucchetti, Donatella, Walker, Cheryl L, Carugo, Alessandro, Giuliani, Virginia, Heffernan, Timothy P, Viale, Andrea, Tannir, Nizar M, Draetta, Giulio F, Msaouel, Pavlo, Genovese, Giannicola, and Lucchetti, Donatella (ORCID:0000-0001-8147-0079)

Abstract

Renal medullary carcinoma (RMC) is an aggressive kidney cancer that almost exclusively develops in individuals with sickle cell trait (SCT) and is always characterized by loss of the tumor suppressor SMARCB1. Because renal ischemia induced by red blood cell sickling exacerbates chronic renal medullary hypoxia in vivo, we investigated whether the loss of SMARCB1 confers a survival advantage under the setting of SCT. Hypoxic stress, which naturally occurs within the renal medulla, is elevated under the setting of SCT. Our findings showed that hypoxia-induced SMARCB1 degradation protected renal cells from hypoxic stress. SMARCB1 wild-type renal tumors exhibited lower levels of SMARCB1 and more aggressive growth in mice harboring the SCT mutation in human hemoglobin A (HbA) than in control mice harboring wild-type human HbA. Consistent with established clinical observations, SMARCB1-null renal tumors were refractory to hypoxia-inducing therapeutic inhibition of angiogenesis. Further, reconstitution of SMARCB1 restored renal tumor sensitivity to hypoxic stress in vitro and in vivo. Together, our results demonstrate a physiological role for SMARCB1 degradation in response to hypoxic stress, connect the renal medullary hypoxia induced by SCT with an increased risk of SMARCB1-negative RMC, and shed light into the mechanisms mediating the resistance of SMARCB1-null renal tumors against angiogenesis inhibition therapies.

Published
2023

Catalog

Books, media, physical & digital resources
See catalog results