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Your search keyword '"Stuart, Josh M."' showing total 3 results
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3 results on '"Stuart, Josh M."'

1. Magnetic resonance perfusion image features uncover an angiogenic subgroup of glioblastoma patients with poor survival and better response to antiangiogenic treatment

Author

Liu, Tiffany T, Achrol, Achal S, Mitchell, Lex A, Rodriguez, Scott A, Feroze, Abdullah, Iv, Michael, Kim, Christine, Chaudhary, Navjot, Gevaert, Olivier, Stuart, Josh M, Harsh, Griffith R, Chang, Steven D, and Rubin, Daniel L

Subjects
Biomedical Imaging, Clinical Trials and Supportive Activities, Neurosciences, Rare Diseases, Cancer, Brain Cancer, Biotechnology, Brain Disorders, Clinical Research, Adult, Aged, Aged, 80 and over, Angiogenesis Inhibitors, Brain Neoplasms, Cluster Analysis, Cohort Studies, Female, Genotype, Glioblastoma, Humans, Kaplan-Meier Estimate, Magnetic Resonance Angiography, Male, Middle Aged, Neovascularization, Pathologic, Treatment Outcome, Young Adult, angiogenesis, antiangiogenic therapy, patient stratification, quantitative perfusion-weighted imaging, radiogenomic analysis, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

BackgroundIn previous clinical trials, antiangiogenic therapies such as bevacizumab did not show efficacy in patients with newly diagnosed glioblastoma (GBM). This may be a result of the heterogeneity of GBM, which has a variety of imaging-based phenotypes and gene expression patterns. In this study, we sought to identify a phenotypic subtype of GBM patients who have distinct tumor-image features and molecular activities and who may benefit from antiangiogenic therapies.MethodsQuantitative image features characterizing subregions of tumors and the whole tumor were extracted from preoperative and pretherapy perfusion magnetic resonance (MR) images of 117 GBM patients in 2 independent cohorts. Unsupervised consensus clustering was performed to identify robust clusters of GBM in each cohort. Cox survival and gene set enrichment analyses were conducted to characterize the clinical significance and molecular pathway activities of the clusters. The differential treatment efficacy of antiangiogenic therapy between the clusters was evaluated.ResultsA subgroup of patients with elevated perfusion features was identified and was significantly associated with poor patient survival after accounting for other clinical covariates (P values 3) consistently found in both cohorts. Angiogenesis and hypoxia pathways were enriched in this subgroup of patients, suggesting the potential efficacy of antiangiogenic therapy. Patients of the angiogenic subgroups pooled from both cohorts, who had chemotherapy information available, had significantly longer survival when treated with antiangiogenic therapy (log-rank P=.022).ConclusionsOur findings suggest that an angiogenic subtype of GBM patients may benefit from antiangiogenic therapy with improved overall survival.

Published
2017

2. 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, Cancer Genome Atlas Network, Zhu, Andrew X, Stuart, Josh M, Sander, Chris, Akbani, Rehan, Cherniack, Andrew D, Deshpande, Vikram, Mounajjed, Taofic, Foo, Wai Chin, Torbenson, Michael S, Kleiner, David E, Laird, Peter W, Wheeler, David A, McRee, Autumn J, Bathe, Oliver F, Andersen, Jesper B, Bardeesy, Nabeel, Roberts, Lewis R, and Kwong, Lawrence N

Subjects
Cancer Genome Atlas Network, Liver, Chromatin, Mitochondria, Humans, Cholangiocarcinoma, Bile Duct Neoplasms, Liver Neoplasms, Pancreatic Neoplasms, Isocitrate Dehydrogenase, Nuclear Proteins, Transcription Factors, RNA, Messenger, Genomics, DNA Methylation, Gene Expression Regulation, Neoplastic, Mutation, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Promoter Regions, Genetic, RNA, Long Noncoding, ARID1A, DNA methylation, IDH, RNA sequencing, TCGA, cholangiocarcinoma, integrative genomics, lncRNAs, multi-omics, whole exome, RNA, Messenger, Gene Expression Regulation, Neoplastic, and over, Promoter Regions, Genetic, Long Noncoding, 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

3. Comprehensive molecular characterization of gastric adenocarcinoma

Author

Bass, Adam J., Thorsson, Vesteinn, Shmulevich, Ilya, Reynolds, Sheila M., Miller, Michael, Bernard, Brady, Hinoue, Toshinori, Laird, Peter W., Curtis, Christina, Shen, Hui, Weisenberger, Daniel J., Schultz, Nikolaus, Shen, Ronglai, Weinhold, Nils, Kelsen, David P., Bowlby, Reanne, Chu, Andy, Kasaian, Katayoon, Mungall, Andrew J., Robertson, A. Gordon, Sipahimalani, Payal, Cherniack, Andrew, Getz, Gad, Liu, Yingchun, Noble, Michael S., Pedamallu, Chandra, Sougnez, Carrie, Taylor-Weiner, Amaro, Akbani, Rehan, Lee, Ju-Seog, Liu, Wenbin, Mills, Gordon B., Yang, Da, Zhang, Wei, Pantazi, Angeliki, Parfenov, Michael, Gulley, Margaret, Piazuelo, M. Blanca, Schneider, Barbara G., Kim, Jihun, Boussioutas, Alex, Sheth, Margi, Demchok, John A., Rabkin, Charles S., Willis, Joseph E., Ng, Sam, Garman, Katherine, Beer, David G., Pennathur, Arjun, Raphael, Benjamin J., Wu, Hsin-Ta, Odze, Robert, Kim, Hark K., Bowen, Jay, Leraas, Kristen M., Lichtenberg, Tara M., Weaver, Stephanie, McLellan, Michael, Wiznerowicz, Maciej, Sakai, Ryo, Lawrence, Michael S., Cibulskis, Kristian, Lichtenstein, Lee, Fisher, Sheila, Gabriel, Stacey B., Lander, Eric S., Ding, Li, Niu, Beifang, Ally, Adrian, Balasundaram, Miruna, Birol, Inanc, Brooks, Denise, Butterfield, Yaron S. N., Carlsen, Rebecca, Chu, Justin, Chuah, Eric, Chun, Hye-Jung E., Clarke, Amanda, Dhalla, Noreen, Guin, Ranabir, Holt, Robert A., Jones, Steven J.M., Lee, Darlene, Li, Haiyan A., Lim, Emilia, Ma, Yussanne, Marra, Marco A., Mayo, Michael, Moore, Richard A., Mungall, Karen L., Nip, Ka Ming, Schein, Jacqueline E., Tam, Angela, Thiessen, Nina, Beroukhim, Rameen, Carter, Scott L., Cherniack, Andrew D., Cho, Juok, DiCara, Daniel, Frazer, Scott, Gehlenborg, Nils, Heiman, David I., Jung, Joonil, Kim, Jaegil, Lin, Pei, Meyerson, Matthew, Ojesina, Akinyemi I., Pedamallu, Chandra Sekhar, Saksena, Gordon, Schumacher, Steven E., Stojanov, Petar, Tabak, Barbara, Voet, Doug, Rosenberg, Mara, Zack, Travis I., Zhang, Hailei, Zou, Lihua, Protopopov, Alexei, Santoso, Netty, Lee, Semin, Zhang, Jianhua, Mahadeshwar, Harshad S., Tang, Jiabin, Ren, Xiaojia, Seth, Sahil, Yang, Lixing, Xu, Andrew W., Song, Xingzhi, Xi, Ruibin, Bristow, Christopher A., Hadjipanayis, Angela, Seidman, Jonathan, Chin, Lynda, Park, Peter J., Kucherlapati, Raju, Ling, Shiyun, Rao, Arvind, Weinstein, John N., Kim, Sang-Bae, Lu, Yiling, Mills, Gordon, Bootwalla, Moiz S., Lai, Phillip H., Triche, Timothy, Van Den Berg, David J., Baylin, Stephen B., Herman, James G., Murray, Bradley A., Askoy, B. Arman, Ciriello, Giovanni, Dresdner, Gideon, Gao, Jianjiong, Gross, Benjamin, Jacobsen, Anders, Lee, William, Ramirez, Ricardo, Sander, Chris, Senbabaoglu, Yasin, Sinha, Rileen, Sumer, S. Onur, Sun, Yichao, Thorsson, Vésteinn, Iype, Lisa, Kramer, Roger W., Kreisberg, Richard, Rovira, Hector, Tasman, Natalie, Ng, Santa Cruz Sam, Haussler, David, Stuart, Josh M., Verhaak, Roeland G.W., Leiserson, Mark D. M., Taylor, Barry S., Black, Aaron D., Carney, Julie Ann, Gastier-Foster, Julie M., Helsel, Carmen, McAllister, Cynthia, Ramirez, Nilsa C., Tabler, Teresa R., Wise, Lisa, Zmuda, Erik, Penny, Robert, Crain, Daniel, Gardner, Johanna, Lau, Kevin, Curely, Erin, Mallery, David, Morris, Scott, Paulauskis, Joseph, Shelton, Troy, Shelton, Candace, Sherman, Mark, Benz, Christopher, Lee, Jae-Hyuk, Fedosenko, Konstantin, Manikhas, Georgy, Potapova, Olga, Voronina, Olga, Belyaev, Smitry, Dolzhansky, Oleg, Rathmell, W. Kimryn, Brzezinski, Jakub, Ibbs, Matthew, Korski, Konstanty, Kycler, Witold, ŁaŸniak, Radoslaw, Leporowska, Ewa, Mackiewicz, Andrzej, Murawa, Dawid, Murawa, Pawel, Spychała, Arkadiusz, Suchorska, Wiktoria M., Tatka, Honorata, Teresiak, Marek, Abdel-Misih, Raafat, Bennett, Joseph, Brown, Jennifer, Iacocca, Mary, Rabeno, Brenda, Kwon, Sun-Young, Kemkes, Ariane, Curley, Erin, Alexopoulou, Iakovina, Engel, Jay, Bartlett, John, Albert, Monique, Park, Do-Youn, Dhir, Rajiv, Luketich, James, Landreneau, Rodney, Janjigian, Yelena Y., Cho, Eunjung, Ladanyi, Marc, Tang, Laura, McCall, Shannon J., Park, Young S., Cheong, Jae-Ho, Ajani, Jaffer, Camargo, M. Constanza, Alonso, Shelley, Ayala, Brenda, Jensen, Mark A., Pihl, Todd, Raman, Rohini, Walton, Jessica, Wan, Yunhu, Eley, Greg, Mills Shaw, Kenna R., Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Zenklusen, Jean Claude, Davidsen, Tanja, Hutter, Carolyn M., Sofia, Heidi J., Burton, Robert, Chudamani, Sudha, Liu, Jia, Broad Institute of MIT and Harvard, Massachusetts Institute of Technology. Department of Biology, Getz, Gad Asher, Sougnez, Carrie L, Jung, Joonil, Lander, Eric Steven, Lin, Pei, Meyerson, Matthew L, and Voet, Douglas

Subjects
Male, Herpesvirus 4, Human, Proteome, Biology, Adenocarcinoma, Bioinformatics, MLH1, Article, Epstein-Barr virus associated gastric carcinoma, Germline mutation, Stomach Neoplasms, medicine, Humans, Multidisciplinary, CpG Island Methylator Phenotype, Genome, Human, digestive, oral, and skin physiology, medicine.disease, digestive system diseases, Lynch syndrome, 3. Good health, Gene Expression Regulation, Neoplastic, Mutation, Cancer research, Female, DNA mismatch repair, Gastric Carcinoma with Lymphoid Stroma
Abstract

Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein-Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also known as PD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies., National Institutes of Health (U.S.) (Grant 5U24CA143799), National Institutes of Health (U.S.) (Grant 5U24CA143835), National Institutes of Health (U.S.) (Grant 5U24CA143840), National Institutes of Health (U.S.) (Grant 5U24CA143843), National Institutes of Health (U.S.) (Grant 5U24CA143845), National Institutes of Health (U.S.) (Grant 5U24CA143848), National Institutes of Health (U.S.) (Grant 5U24CA143858), National Institutes of Health (U.S.) (Grant 5U24CA143866), National Institutes of Health (U.S.) (Grant 5U24CA143867), National Institutes of Health (U.S.) (Grant 5U24CA143882), National Institutes of Health (U.S.) (Grant 5U24CA143883), National Institutes of Health (U.S.) (Grant 5U24CA144025), National Institutes of Health (U.S.) (Grant U54HG003067), National Institutes of Health (U.S.) (Grant U54HG003079), National Institutes of Health (U.S.) (Grant U54HG003273), National Institutes of Health (U.S.) (Grant P30CA16672)

Published
2014

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