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1,078 results on '"Chin, Lynda"'

1. Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer

Author

Akdemir, Kadir C, Le, Victoria T, Chandran, Sahaana, Li, Yilong, Verhaak, Roel G, Beroukhim, Rameen, Campbell, Peter J, Chin, Lynda, Dixon, Jesse R, and Futreal, P Andrew

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Genetics, Human Genome, Cancer, Biotechnology, Aetiology, 2.1 Biological and endogenous factors, Chromatin, Gene Expression Regulation, Neoplastic, Gene Rearrangement, Genome, Human, Genomic Structural Variation, Humans, Neoplasms, PCAWG Structural Variation Working Group, PCAWG Consortium, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Chromatin is folded into successive layers to organize linear DNA. Genes within the same topologically associating domains (TADs) demonstrate similar expression and histone-modification profiles, and boundaries separating different domains have important roles in reinforcing the stability of these features. Indeed, domain disruptions in human cancers can lead to misregulation of gene expression. However, the frequency of domain disruptions in human cancers remains unclear. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), which aggregated whole-genome sequencing data from 2,658 cancers across 38 tumor types, we analyzed 288,457 somatic structural variations (SVs) to understand the distributions and effects of SVs across TADs. Notably, SVs can lead to the fusion of discrete TADs, and complex rearrangements markedly change chromatin folding maps in the cancer genomes. Notably, only 14% of the boundary deletions resulted in a change in expression in nearby genes of more than twofold.

Published
2020

2. Corrigendum: miR-182 integrates apoptosis, growth, and differentiation programs in glioblastoma

Author

Kouri, Fotini M., primary, Hurley, Lisa A., additional, Daniel, Weston L., additional, Day, Emily S., additional, Hua, Youjia, additional, Hao, Liangliang, additional, Peng, Chian-Yu, additional, Merkel, Timothy J., additional, Queisser, Markus A., additional, Ritner, Carissa, additional, Zhang, Hailei, additional, James, C. David, additional, Sznajder, Jacob I., additional, Chin, Lynda, additional, Giljohann, David A., additional, Kessler, John A., additional, Peter, Marcus E., additional, Mirkin, Chad A., additional, and Stegh, Alexander H., additional

Published
2024
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4. The Integrated Genomic Landscape of Thymic Epithelial Tumors

Author

Radovich, Milan, Pickering, Curtis R, Felau, Ina, Ha, Gavin, Zhang, Hailei, Jo, Heejoon, Hoadley, Katherine A, Anur, Pavana, Zhang, Jiexin, McLellan, Mike, Bowlby, Reanne, Matthew, Thomas, Danilova, Ludmila, Hegde, Apurva M, Kim, Jaegil, Leiserson, Mark DM, Sethi, Geetika, Lu, Charles, Ryan, Michael, Su, Xiaoping, Cherniack, Andrew D, Robertson, Gordon, Akbani, Rehan, Spellman, Paul, Weinstein, John N, Hayes, D Neil, Raphael, Ben, Lichtenberg, Tara, Leraas, Kristen, Zenklusen, Jean Claude, Network, The Cancer Genome Atlas, Ally, Adrian, Appelbaum, Elizabeth L, Auman, J Todd, Balasundaram, Miruna, Balu, Saianand, Behera, Madhusmita, Beroukhim, Rameen, Berrios, Mario, Blandino, Giovanni, Bodenheimer, Tom, Bootwalla, Moiz S, Bowen, Jay, Brooks, Denise, Carcano, Flavio M, Carlsen, Rebecca, Carvalho, Andre L, Castro, Patricia, Chalabreysse, Lara, Chin, Lynda, Cho, Juok, Choe, Gina, Chuah, Eric, Chudamani, Sudha, Cibulskis, Carrie, Cope, Leslie, Cordes, Matthew G, Crain, Daniel, Curley, Erin, Defreitas, Timothy, Demchok, John A, Detterbeck, Frank, Dhalla, Noreen, Dienemann, Hendrik, Edenfield, W Jeff, Facciolo, Francesco, Ferguson, Martin L, Frazer, Scott, Fronick, Catrina C, Fulton, Lucinda A, Fulton, Robert S, Gabriel, Stacey B, Gardner, Johanna, Gastier-Foster, Julie M, Gehlenborg, Nils, Gerken, Mark, Getz, Gad, Heiman, David I, Hobensack, Shital, Holbrook, Andrea, Holt, Robert A, Hoyle, Alan P, Hutter, Carolyn M, Ittmann, Michael, Jefferys, Stuart R, Jones, Corbin D, Jones, Steven JM, Kasaian, Katayoon, Kimes, Patrick K, Lai, Phillip H, Laird, Peter W, Lawrence, Michael S, Lin, Pei, Liu, Jia, Lolla, Laxmi, Lu, Yiling, Ma, Yussanne, Maglinte, Dennis T, and Mallery, David

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Autoimmune Disease, Biotechnology, Human Genome, Cancer, Rare Diseases, 2.1 Biological and endogenous factors, Aetiology, Adolescent, Adult, Aged, Aged, 80 and over, Female, Genomics, Humans, Male, Middle Aged, Mutation, Neoplasms, Glandular and Epithelial, Thymoma, Thymus Neoplasms, Transcription Factors, TFII, Young Adult, Cancer Genome Atlas Network, TCGA, autoimmunity, genomics, myasthenia gravis, proteomics, thymic carcinoma, thymic epithelial tumors, thymoma, transcriptomics, Neurosciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

Thymic epithelial tumors (TETs) are one of the rarest adult malignancies. Among TETs, thymoma is the most predominant, characterized by a unique association with autoimmune diseases, followed by thymic carcinoma, which is less common but more clinically aggressive. Using multi-platform omics analyses on 117 TETs, we define four subtypes of these tumors defined by genomic hallmarks and an association with survival and World Health Organization histological subtype. We further demonstrate a marked prevalence of a thymoma-specific mutated oncogene, GTF2I, and explore its biological effects on multi-platform analysis. We further observe enrichment of mutations in HRAS, NRAS, and TP53. Last, we identify a molecular link between thymoma and the autoimmune disease myasthenia gravis, characterized by tumoral overexpression of muscle autoantigens, and increased aneuploidy.

Published
2018

5. Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas

Author

Network, The Cancer Genome Atlas Research, Abeshouse, Adam, Adebamowo, Clement, Adebamowo, Sally N, Akbani, Rehan, Akeredolu, Teniola, Ally, Adrian, Anderson, Matthew L, Anur, Pavana, Appelbaum, Elizabeth L, Armenia, Joshua, Auman, J Todd, Bailey, Matthew H, Baker, Laurence, Balasundaram, Miruna, Balu, Saianand, Barthel, Floris P, Bartlett, John, Baylin, Stephen B, Behera, Madhusmita, Belyaev, Dmitry, Bennett, Joesph, Benz, Christopher, Beroukhim, Rameen, Birrer, Michael, Bocklage, Thèrése, Bodenheimer, Tom, Boice, Lori, Bootwalla, Moiz S, Bowen, Jay, Bowlby, Reanne, Boyd, Jeff, Brohl, Andrew S, Brooks, Denise, Byers, Lauren, Carlsen, Rebecca, Castro, Patricia, Chen, Hsiao-Wei, Cherniack, Andrew D, Chibon, Fréderic, Chin, Lynda, Cho, Juok, Chuah, Eric, Chudamani, Sudha, Cibulskis, Carrie, Cooper, Lee AD, Cope, Leslie, Cordes, Matthew G, Crain, Daniel, Curley, Erin, Danilova, Ludmila, Dao, Fanny, Davis, Ian J, Davis, Lara E, Defreitas, Timothy, Delman, Keith, Demchok, John A, Demetri, George D, Demicco, Elizabeth G, Dhalla, Noreen, Diao, Lixia, Ding, Li, DiSaia, Phil, Dottino, Peter, Doyle, Leona A, Drill, Esther, Dubina, Michael, Eschbacher, Jennifer, Fedosenko, Konstantin, Felau, Ina, Ferguson, Martin L, Frazer, Scott, Fronick, Catrina C, Fulidou, Victoria, Fulton, Lucinda A, Fulton, Robert S, Gabriel, Stacey B, Gao, Jianjiong, Gao, Qingsong, Gardner, Johanna, Gastier-Foster, Julie M, Gay, Carl M, Gehlenborg, Nils, Gerken, Mark, Getz, Gad, Godwin, Andrew K, Godwin, Eryn M, Gordienko, Elena, Grilley-Olson, Juneko E, Gutman, David A, Gutmann, David H, Hayes, D Neil, Hegde, Apurva M, Heiman, David I, Heins, Zachary, Helsel, Carmen, Hepperla, Austin J, Higgins, Kelly, Hoadley, Katherine A, and Hobensack, Shital

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Oncology and Carcinogenesis, Cancer, Human Genome, Digestive Diseases, Rare Diseases, Adult, Aged, Aged, 80 and over, Cluster Analysis, DNA Copy Number Variations, Epigenomics, Genome, Human, Genome-Wide Association Study, Humans, Middle Aged, Mutation, Sarcoma, Young Adult, Cancer Genome Atlas Research Network. Electronic address: elizabeth.demicco@sinaihealthsystem.ca, Cancer Genome Atlas Research Network, DNA methylation, The Cancer Genome Atlas, dedifferentiated liposarcoma, genomics, immune infiltration, leiomyosarcoma, molecular subtype, myxofibrosarcoma, pleomorphism, undifferentiated pleomorphic sarcoma, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (TP53, ATRX, RB1) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types.

Published
2017

7. Integrative Analysis Identifies Four Molecular and Clinical Subsets in Uveal Melanoma

Author

Robertson, A Gordon, Shih, Juliann, Yau, Christina, Gibb, Ewan A, Oba, Junna, Mungall, Karen L, Hess, Julian M, Uzunangelov, Vladislav, Walter, Vonn, Danilova, Ludmila, Lichtenberg, Tara M, Kucherlapati, Melanie, Kimes, Patrick K, Tang, Ming, Penson, Alexander, Babur, Ozgun, Akbani, Rehan, Bristow, Christopher A, Hoadley, Katherine A, Iype, Lisa, Chang, Matthew T, Network, TCGA Research, Abdel-Rahman, Mohamed H, Ally, Adrian, Auman, J Todd, Balasundaram, Miruna, Balu, Saianand, Benz, Christopher, Beroukhim, Rameen, Birol, Inanc, Bodenheimer, Tom, Bowen, Jay, Bowlby, Reanne, Brooks, Denise, Carlsen, Rebecca, Cebulla, Colleen M, Cherniack, Andrew D, Chin, Lynda, Cho, Juok, Chuah, Eric, Chudamani, Sudha, Cibulskis, Carrie, Cibulskis, Kristian, Cope, Leslie, Coupland, Sarah E, Defreitas, Timothy, Demchok, John A, Desjardins, Laurence, Dhalla, Noreen, Esmaeli, Bita, Felau, Ina, Ferguson, Martin L, Frazer, Scott, Gabriel, Stacey B, Gastier-Foster, Julie M, Gehlenborg, Nils, Gerken, Mark, Gershenwald, Jeffrey E, Getz, Gad, Griewank, Klaus G, Grimm, Elizabeth A, Hayes, D Neil, Hegde, Apurva M, Heiman, David I, Helsel, Carmen, Hobensack, Shital, Holt, Robert A, Hoyle, Alan P, Hu, Xin, Hutter, Carolyn M, Jager, Martine J, Jefferys, Stuart R, Jones, Corbin D, Jones, Steven JM, Kandoth, Cyriac, Kasaian, Katayoon, Kim, Jaegil, Kucherlapati, Raju, Lander, Eric, Lawrence, Michael S, Lazar, Alexander J, Lee, Semin, Leraas, Kristen M, Lin, Pei, Liu, Jia, Liu, Wenbin, Lolla, Laxmi, and Lu, Yiling

Subjects
Eye Disease and Disorders of Vision, Cancer, Human Genome, Rare Diseases, Genetics, Biomarkers, Tumor, DNA Copy Number Variations, DNA Methylation, Eukaryotic Initiation Factor-1, Gene Expression Regulation, Neoplastic, Humans, Melanoma, Monosomy, Mutation, Phosphoproteins, Prognosis, RNA Splicing Factors, Serine-Arginine Splicing Factors, Tumor Suppressor Proteins, Ubiquitin Thiolesterase, Uveal Neoplasms, TCGA Research Network, EIF1AX, GNA11, GNAQ, SF3B1, SRSF2, TCGA, molecular subtypes, monosomy 3, noncoding RNA, uveal melanoma, Neurosciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

Comprehensive multiplatform analysis of 80 uveal melanomas (UM) identifies four molecularly distinct, clinically relevant subtypes: two associated with poor-prognosis monosomy 3 (M3) and two with better-prognosis disomy 3 (D3). We show that BAP1 loss follows M3 occurrence and correlates with a global DNA methylation state that is distinct from D3-UM. Poor-prognosis M3-UM divide into subsets with divergent genomic aberrations, transcriptional features, and clinical outcomes. We report change-of-function SRSF2 mutations. Within D3-UM, EIF1AX- and SRSF2/SF3B1-mutant tumors have distinct somatic copy number alterations and DNA methylation profiles, providing insight into the biology of these low- versus intermediate-risk clinical mutation subtypes.

Published
2017

8. Comprehensive and Integrative Genomic Characterization of Hepatocellular Carcinoma

Author

Ally, Adrian, Balasundaram, Miruna, Carlsen, Rebecca, Chuah, Eric, Clarke, Amanda, Dhalla, Noreen, Holt, Robert A, Jones, Steven JM, Lee, Darlene, Ma, Yussanne, Marra, Marco A, Mayo, Michael, Moore, Richard A, Mungall, Andrew J, Schein, Jacqueline E, Sipahimalani, Payal, Tam, Angela, Thiessen, Nina, Cheung, Dorothy, Wong, Tina, Brooks, Denise, Robertson, A Gordon, Bowlby, Reanne, Mungall, Karen, Sadeghi, Sara, Xi, Liu, Covington, Kyle, Shinbrot, Eve, Wheeler, David A, Gibbs, Richard A, Donehower, Lawrence A, Wang, Linghua, Bowen, Jay, Gastier-Foster, Julie M, Gerken, Mark, Helsel, Carmen, Leraas, Kristen M, Lichtenberg, Tara M, Ramirez, Nilsa C, Wise, Lisa, Zmuda, Erik, Gabriel, Stacey B, Meyerson, Matthew, Cibulskis, Carrie, Murray, Bradley A, Shih, Juliann, Beroukhim, Rameen, Cherniack, Andrew D, Schumacher, Steven E, Saksena, Gordon, Pedamallu, Chandra Sekhar, Chin, Lynda, Getz, Gad, Noble, Michael, Zhang, Hailei, Heiman, David, Cho, Juok, Gehlenborg, Nils, Voet, Douglas, Lin, Pei, Frazer, Scott, Defreitas, Timothy, Meier, Sam, Lawrence, Michael, Kim, Jaegil, Creighton, Chad J, Muzny, Donna, Doddapaneni, HarshaVardhan, Hu, Jianhong, Wang, Min, Morton, Donna, Korchina, Viktoriya, Han, Yi, Dinh, Huyen, Lewis, Lora, Bellair, Michelle, Liu, Xiuping, Santibanez, Jireh, Glenn, Robert, Lee, Sandra, Hale, Walker, Parker, Joel S, Wilkerson, Matthew D, Hayes, D Neil, Reynolds, Sheila M, Shmulevich, Ilya, Zhang, Wei, Liu, Yuexin, Iype, Lisa, Makhlouf, Hala, Torbenson, Michael S, Kakar, Sanjay, Yeh, Matthew M, Jain, Dhanpat, Kleiner, David E, Dhanasekaran, Renumathy, El-Serag, Hashem B, and Yim, Sun Young

Subjects
Human Genome, Digestive Diseases, Biotechnology, Rare Diseases, Genetics, Liver Disease, Liver Cancer, Cancer, Aetiology, 2.1 Biological and endogenous factors, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, Good Health and Well Being, Carcinoma, Hepatocellular, DNA Methylation, Genomics, Humans, Isocitrate Dehydrogenase, Liver Neoplasms, MicroRNAs, Mutation, Cancer Genome Atlas Research Network. Electronic address: wheeler@bcm.edu, Cancer Genome Atlas Research Network, IDH1/2, TP53, cancer subtyping, expression profile, hepatocellular carcinoma, metabolic reprogramming, promoter hypermethylation, significantly mutated genes, sonic hedgehog signaling, stem cell phenotype, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Liver cancer has the second highest worldwide cancer mortality rate and has limited therapeutic options. We analyzed 363 hepatocellular carcinoma (HCC) cases by whole-exome sequencing and DNA copy number analyses, and we analyzed 196 HCC cases by DNA methylation, RNA, miRNA, and proteomic expression also. DNA sequencing and mutation analysis identified significantly mutated genes, including LZTR1, EEF1A1, SF3B1, and SMARCA4. Significant alterations by mutation or downregulation by hypermethylation in genes likely to result in HCC metabolic reprogramming (ALB, APOB, and CPS1) were observed. Integrative molecular HCC subtyping incorporating unsupervised clustering of five data platforms identified three subtypes, one of which was associated with poorer prognosis in three HCC cohorts. Integrated analyses enabled development of a p53 target gene expression signature correlating with poor survival. Potential therapeutic targets for which inhibitors exist include WNT signaling, MDM4, MET, VEGFA, MCL1, IDH1, TERT, and immune checkpoint proteins CTLA-4, PD-1, and PD-L1.

Published
2017

9. Systematic Epigenomic Analysis Reveals Chromatin States Associated with Melanoma Progression

Author

Fiziev, Petko, Akdemir, Kadir C, Miller, John P, Keung, Emily Z, Samant, Neha S, Sharma, Sneha, Natale, Christopher A, Terranova, Christopher J, Maitituoheti, Mayinuer, Amin, Samirkumar B, Martinez-Ledesma, Emmanuel, Dhamdhere, Mayura, Axelrad, Jacob B, Shah, Amiksha, Cheng, Christine S, Mahadeshwar, Harshad, Seth, Sahil, Barton, Michelle C, Protopopov, Alexei, Tsai, Kenneth Y, Davies, Michael A, Garcia, Benjamin A, Amit, Ido, Chin, Lynda, Ernst, Jason, and Rai, Kunal

Subjects
Biological Sciences, Human Genome, Cancer, Genetics, Aetiology, 2.1 Biological and endogenous factors, Acetylation, Cell Line, Cell Proliferation, Chromatin, Chromatin Immunoprecipitation, Disease-Free Survival, Epigenomics, Histone Deacetylase Inhibitors, Histone Deacetylases, Histones, Humans, Hydroxamic Acids, Kaplan-Meier Estimate, Melanoma, PTEN Phosphohydrolase, Principal Component Analysis, RNA Interference, RNA, Small Interfering, Signal Transduction, Vorinostat, CBP, ChIP-seq, DUSP5, HDAC, chromatin state, epigenome, histone modifications, melanoma, Biochemistry and Cell Biology, Medical Physiology, Biological sciences
Abstract

The extent and nature of epigenomic changes associated with melanoma progression is poorly understood. Through systematic epigenomic profiling of 35 epigenetic modifications and transcriptomic analysis, we define chromatin state changes associated with melanomagenesis by using a cell phenotypic model of non-tumorigenic and tumorigenic states. Computation of specific chromatin state transitions showed loss of histone acetylations and H3K4me2/3 on regulatory regions proximal to specific cancer-regulatory genes in important melanoma-driving cell signaling pathways. Importantly, such acetylation changes were also observed between benign nevi and malignant melanoma human tissues. Intriguingly, only a small fraction of chromatin state transitions correlated with expected changes in gene expression patterns. Restoration of acetylation levels on deacetylated loci by histone deacetylase (HDAC) inhibitors selectively blocked excessive proliferation in tumorigenic cells and human melanoma cells, suggesting functional roles of observed chromatin state transitions in driving hyperproliferative phenotype. Through these results, we define functionally relevant chromatin states associated with melanoma progression.

Published
2017

10. 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

11. Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma

Author

Fishbein, Lauren, Leshchiner, Ignaty, Walter, Vonn, Danilova, Ludmila, Robertson, A Gordon, Johnson, Amy R, Lichtenberg, Tara M, Murray, Bradley A, Ghayee, Hans K, Else, Tobias, Ling, Shiyun, Jefferys, Stuart R, de Cubas, Aguirre A, Wenz, Brandon, Korpershoek, Esther, Amelio, Antonio L, Makowski, Liza, Rathmell, W Kimryn, Gimenez-Roqueplo, Anne-Paule, Giordano, Thomas J, L., Sylvia, Tischler, Arthur S, Network, The Cancer Genome Atlas Research, Akbani, Rehan, Ally, Adrian, Amar, Laurence, Arachchi, Harindra, Auchus, Richard J, Auman, J Todd, Baertsch, Robert, Balasundaram, Miruna, Balu, Saianand, Bartsch, Detlef K, Baudin, Eric, Bauer, Thomas, Beaver, Allison, Benz, Christopher, Beroukhim, Rameen, Beuschlein, Felix, Bodenheimer, Tom, Boice, Lori, Bowen, Jay, Bowlby, Reanne, Brooks, Denise, Carlsen, Rebecca, Carter, Suzie, Cassol, Clarissa A, Cherniack, Andrew D, Chin, Lynda, Cho, Juok, Chuah, Eric, Chudamani, Sudha, Cope, Leslie, Crain, Daniel, Curley, Erin, de Krijger, Ronald R, Demchok, John A, Deutschbein, Timo, Dhalla, Noreen, Dimmock, David, Dinjens, Winand NM, Eng, Charis, Eschbacher, Jennifer, Fassnacht, Martin, Felau, Ina, Feldman, Michael, Ferguson, Martin L, Fiddes, Ian, Frazer, Scott, Gabriel, Stacey B, Gardner, Johanna, Gastier-Foster, Julie M, Gehlenborg, Nils, Gerken, Mark, Getz, Gad, Geurts, Jennifer, Goldman, Mary, Graim, Kiley, Gupta, Manaswi, Haan, David, Hahner, Stefanie, Hantel, Constanze, Haussler, David, Hayes, D Neil, Heiman, David I, Hoadley, Katherine A, Holt, Robert A, Hoyle, Alan P, Huang, Mei, Hunt, Bryan, and Hutter, Carolyn M

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Neurosciences, Precision Medicine, Cancer, Human Genome, Cancer Genomics, Biotechnology, Rare Diseases, 2.1 Biological and endogenous factors, Aetiology, Good Health and Well Being, Adult, Aged, Aged, 80 and over, DNA-Binding Proteins, Female, Gene Fusion, Humans, Male, Middle Aged, Mutation, Nuclear Proteins, Paraganglioma, Pheochromocytoma, Pol1 Transcription Initiation Complex Proteins, Proto-Oncogene Proteins c-ret, RNA-Binding Proteins, Trans-Activators, Transcription Factors, Cancer Genome Atlas Research Network, CSDE1, MAML3, TCGA, expression subtypes, genomics, metastasis, molecular profiling, paraganglioma, pheochromocytoma, sequencing, Oncology and Carcinogenesis, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

We report a comprehensive molecular characterization of pheochromocytomas and paragangliomas (PCCs/PGLs), a rare tumor type. Multi-platform integration revealed that PCCs/PGLs are driven by diverse alterations affecting multiple genes and pathways. Pathogenic germline mutations occurred in eight PCC/PGL susceptibility genes. We identified CSDE1 as a somatically mutated driver gene, complementing four known drivers (HRAS, RET, EPAS1, and NF1). We also discovered fusion genes in PCCs/PGLs, involving MAML3, BRAF, NGFR, and NF1. Integrated analysis classified PCCs/PGLs into four molecularly defined groups: a kinase signaling subtype, a pseudohypoxia subtype, a Wnt-altered subtype, driven by MAML3 and CSDE1, and a cortical admixture subtype. Correlates of metastatic PCCs/PGLs included the MAML3 fusion gene. This integrated molecular characterization provides a comprehensive foundation for developing PCC/PGL precision medicine.

Published
2017

12. Epigenetic Activation of WNT5A Drives Glioblastoma Stem Cell Differentiation and Invasive Growth

Author

Hu, Baoli, Wang, Qianghu, Wang, Y Alan, Hua, Sujun, Sauvé, Charles-Etienne Gabriel, Ong, Derrick, Lan, Zheng D, Chang, Qing, Ho, Yan Wing, Monasterio, Marta Moreno, Lu, Xin, Zhong, Yi, Zhang, Jianhua, Deng, Pingna, Tan, Zhi, Wang, Guocan, Liao, Wen-Ting, Corley, Lynda J, Yan, Haiyan, Zhang, Junxia, You, Yongping, Liu, Ning, Cai, Linbo, Finocchiaro, Gaetano, Phillips, Joanna J, Berger, Mitchel S, Spring, Denise J, Hu, Jian, Sulman, Erik P, Fuller, Gregory N, Chin, Lynda, Verhaak, Roeland GW, and DePinho, Ronald A

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Neurosciences, Cancer, Stem Cell Research - Nonembryonic - Non-Human, Stem Cell Research - Nonembryonic - Human, Rare Diseases, Genetics, Brain Cancer, Brain Disorders, Stem Cell Research, Endothelial Cells, Epigenomics, Gene Expression Regulation, Neoplastic, Glioblastoma, Homeodomain Proteins, Humans, Neoplasm Invasiveness, Neural Stem Cells, PAX6 Transcription Factor, Proto-Oncogene Proteins c-akt, Transcription Factors, Wnt-5a Protein, cancer stem cell differentiation, glioblastoma, recurrence, tumor microenvironment, Biological Sciences, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Glioblastoma stem cells (GSCs) are implicated in tumor neovascularization, invasiveness, and therapeutic resistance. To illuminate mechanisms governing these hallmark features, we developed a de novo glioblastoma multiforme (GBM) model derived from immortalized human neural stem/progenitor cells (hNSCs) to enable precise system-level comparisons of pre-malignant and oncogene-induced malignant states of NSCs. Integrated transcriptomic and epigenomic analyses uncovered a PAX6/DLX5 transcriptional program driving WNT5A-mediated GSC differentiation into endothelial-like cells (GdECs). GdECs recruit existing endothelial cells to promote peritumoral satellite lesions, which serve as a niche supporting the growth of invasive glioma cells away from the primary tumor. Clinical data reveal higher WNT5A and GdECs expression in peritumoral and recurrent GBMs relative to matched intratumoral and primary GBMs, respectively, supporting WNT5A-mediated GSC differentiation and invasive growth in disease recurrence. Thus, the PAX6/DLX5-WNT5A axis governs the diffuse spread of glioma cells throughout the brain parenchyma, contributing to the lethality of GBM.

Published
2016

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

Author

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

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

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

Published
2016

14. Dual Roles of RNF2 in Melanoma Progression

Author

Rai, Kunal, Akdemir, Kadir C, Kwong, Lawrence N, Fiziev, Petko, Wu, Chang-Jiun, Keung, Emily Z, Sharma, Sneha, Samant, Neha S, Williams, Maura, Axelrad, Jacob B, Shah, Amiksha, Yang, Dong, Grimm, Elizabeth A, Barton, Michelle C, Milton, Denai R, Heffernan, Timothy P, Horner, James W, Ekmekcioglu, Suhendan, Lazar, Alexander J, Ernst, Jason, and Chin, Lynda

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Biological Sciences, Genetics, Biotechnology, Cancer, 1.1 Normal biological development and functioning, Underpinning research, 2.1 Biological and endogenous factors, Aetiology, Animals, Catalysis, Cell Transformation, Neoplastic, Cyclin D2, Disease Progression, E1A-Associated p300 Protein, Gene Expression, Gene Expression Regulation, Neoplastic, Histone Demethylases, Humans, Latent TGF-beta Binding Proteins, MAP Kinase Signaling System, Melanoma, Mice, Neoplasm Metastasis, Nuclear Proteins, Oncogenes, Phosphorylation, Polycomb Repressive Complex 1, Prognosis, Promoter Regions, Genetic, Transforming Growth Factor beta, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

UnlabelledEpigenetic regulators have emerged as critical factors governing the biology of cancer. Here, in the context of melanoma, we show that RNF2 is prognostic, exhibiting progression-correlated expression in human melanocytic neoplasms. Through a series of complementary gain-of-function and loss-of-function studies in mouse and human systems, we establish that RNF2 is oncogenic and prometastatic. Mechanistically, RNF2-mediated invasive behavior is dependent on its ability to monoubiquitinate H2AK119 at the promoter of LTBP2, resulting in silencing of this negative regulator of TGFβ signaling. In contrast, RNF2's oncogenic activity does not require its catalytic activity nor does it derive from its canonical gene repression function. Instead, RNF2 drives proliferation through direct transcriptional upregulation of the cell-cycle regulator CCND2. We further show that MEK1-mediated phosphorylation of RNF2 promotes recruitment of activating histone modifiers UTX and p300 to a subset of poised promoters, which activates gene expression. In summary, RNF2 regulates distinct biologic processes in the genesis and progression of melanoma via different molecular mechanisms.SignificanceThe role of epigenetic regulators in cancer progression is being increasingly appreciated. We show novel roles for RNF2 in melanoma tumorigenesis and metastasis, albeit via different mechanisms. Our findings support the notion that epigenetic regulators, such as RNF2, directly and functionally control powerful gene networks that are vital in multiple cancer processes.

Published
2015

15. The Molecular Taxonomy of Primary Prostate Cancer

Author

Network, The Cancer Genome Atlas Research, Abeshouse, Adam, Ahn, Jaeil, Akbani, Rehan, Ally, Adrian, Amin, Samirkumar, Andry, Christopher D, Annala, Matti, Aprikian, Armen, Armenia, Joshua, Arora, Arshi, Auman, J Todd, Balasundaram, Miruna, Balu, Saianand, Barbieri, Christopher E, Bauer, Thomas, Benz, Christopher C, Bergeron, Alain, Beroukhim, Rameen, Berrios, Mario, Bivol, Adrian, Bodenheimer, Tom, Boice, Lori, Bootwalla, Moiz S, dos Reis, Rodolfo Borges, Boutros, Paul C, Bowen, Jay, Bowlby, Reanne, Boyd, Jeffrey, Bradley, Robert K, Breggia, Anne, Brimo, Fadi, Bristow, Christopher A, Brooks, Denise, Broom, Bradley M, Bryce, Alan H, Bubley, Glenn, Burks, Eric, Butterfield, Yaron SN, Button, Michael, Canes, David, Carlotti, Carlos G, Carlsen, Rebecca, Carmel, Michel, Carroll, Peter R, Carter, Scott L, Cartun, Richard, Carver, Brett S, Chan, June M, Chang, Matthew T, Chen, Yu, Cherniack, Andrew D, Chevalier, Simone, Chin, Lynda, Cho, Juok, Chu, Andy, Chuah, Eric, Chudamani, Sudha, Cibulskis, Kristian, Ciriello, Giovanni, Clarke, Amanda, Cooperberg, Matthew R, Corcoran, Niall M, Costello, Anthony J, Cowan, Janet, Crain, Daniel, Curley, Erin, David, Kerstin, Demchok, John A, Demichelis, Francesca, Dhalla, Noreen, Dhir, Rajiv, Doueik, Alexandre, Drake, Bettina, Dvinge, Heidi, Dyakova, Natalya, Felau, Ina, Ferguson, Martin L, Frazer, Scott, Freedland, Stephen, Fu, Yao, Gabriel, Stacey B, Gao, Jianjiong, Gardner, Johanna, Gastier-Foster, Julie M, Gehlenborg, Nils, Gerken, Mark, Gerstein, Mark B, Getz, Gad, Godwin, Andrew K, Gopalan, Anuradha, Graefen, Markus, Graim, Kiley, Gribbin, Thomas, Guin, Ranabir, Gupta, Manaswi, Hadjipanayis, Angela, Haider, Syed, Hamel, Lucie, and Hayes, D Neil

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Human Genome, Cancer, Genetic Testing, Genetics, Urologic Diseases, Prostate Cancer, Good Health and Well Being, DNA Repair, Epigenesis, Genetic, Gene Expression Regulation, Neoplastic, Gene Fusion, Humans, Male, Mutation, Neoplasm Metastasis, Phosphatidylinositol 3-Kinases, Prostatic Neoplasms, Receptors, Androgen, Signal Transduction, ras Proteins, Cancer Genome Atlas Research Network, Biological Sciences, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

There is substantial heterogeneity among primary prostate cancers, evident in the spectrum of molecular abnormalities and its variable clinical course. As part of The Cancer Genome Atlas (TCGA), we present a comprehensive molecular analysis of 333 primary prostate carcinomas. Our results revealed a molecular taxonomy in which 74% of these tumors fell into one of seven subtypes defined by specific gene fusions (ERG, ETV1/4, and FLI1) or mutations (SPOP, FOXA1, and IDH1). Epigenetic profiles showed substantial heterogeneity, including an IDH1 mutant subset with a methylator phenotype. Androgen receptor (AR) activity varied widely and in a subtype-specific manner, with SPOP and FOXA1 mutant tumors having the highest levels of AR-induced transcripts. 25% of the prostate cancers had a presumed actionable lesion in the PI3K or MAPK signaling pathways, and DNA repair genes were inactivated in 19%. Our analysis reveals molecular heterogeneity among primary prostate cancers, as well as potentially actionable molecular defects.

Published
2015

16. Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer

Author

Ciriello, Giovanni, Gatza, Michael L, Beck, Andrew H, Wilkerson, Matthew D, Rhie, Suhn K, Pastore, Alessandro, Zhang, Hailei, McLellan, Michael, Yau, Christina, Kandoth, Cyriac, Bowlby, Reanne, Shen, Hui, Hayat, Sikander, Fieldhouse, Robert, Lester, Susan C, Tse, Gary MK, Factor, Rachel E, Collins, Laura C, Allison, Kimberly H, Chen, Yunn-Yi, Jensen, Kristin, Johnson, Nicole B, Oesterreich, Steffi, Mills, Gordon B, Cherniack, Andrew D, Robertson, Gordon, Benz, Christopher, Sander, Chris, Laird, Peter W, Hoadley, Katherine A, King, Tari A, Perou, Charles M, Akbani, Rehan, Auman, J Todd, Balasundaram, Miruna, Balu, Saianand, Barr, Thomas, Beck, Andrew, Benz, Stephen, Berrios, Mario, Beroukhim, Rameen, Bodenheimer, Tom, Boice, Lori, Bootwalla, Moiz S, Bowen, Jay, Brooks, Denise, Chin, Lynda, Cho, Juok, Chudamani, Sudha, Davidsen, Tanja, Demchok, John A, Dennison, Jennifer B, Ding, Li, Felau, Ina, Ferguson, Martin L, Frazer, Scott, Gabriel, Stacey B, Gao, JianJiong, Gastier-Foster, Julie M, Gehlenborg, Nils, Gerken, Mark, Getz, Gad, Gibson, William J, Hayes, D Neil, Heiman, David I, Holbrook, Andrea, Holt, Robert A, Hoyle, Alan P, Hu, Hai, Huang, Mei, Hutter, Carolyn M, Hwang, E Shelley, Jefferys, Stuart R, Jones, Steven JM, Ju, Zhenlin, Kim, Jaegil, Lai, Phillip H, Lawrence, Michael S, Leraas, Kristen M, Lichtenberg, Tara M, Lin, Pei, Ling, Shiyun, Liu, Jia, Liu, Wenbin, Lolla, Laxmi, Lu, Yiling, Ma, Yussanne, Maglinte, Dennis T, Mardis, Elaine, Marks, Jeffrey, Marra, Marco A, and McAllister, Cynthia

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Breast Cancer, Clinical Research, Genetics, Clinical Trials and Supportive Activities, Cancer, Antigens, CD, Breast Neoplasms, Cadherins, Carcinoma, Ductal, Breast, Carcinoma, Lobular, Female, Hepatocyte Nuclear Factor 3-alpha, Humans, Models, Molecular, Mutation, Oligonucleotide Array Sequence Analysis, Oncogene Protein v-akt, Transcriptome, TCGA Research Network, Biological Sciences, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Invasive lobular carcinoma (ILC) is the second most prevalent histologic subtype of invasive breast cancer. Here, we comprehensively profiled 817 breast tumors, including 127 ILC, 490 ductal (IDC), and 88 mixed IDC/ILC. Besides E-cadherin loss, the best known ILC genetic hallmark, we identified mutations targeting PTEN, TBX3, and FOXA1 as ILC enriched features. PTEN loss associated with increased AKT phosphorylation, which was highest in ILC among all breast cancer subtypes. Spatially clustered FOXA1 mutations correlated with increased FOXA1 expression and activity. Conversely, GATA3 mutations and high expression characterized luminal A IDC, suggesting differential modulation of ER activity in ILC and IDC. Proliferation and immune-related signatures determined three ILC transcriptional subtypes associated with survival differences. Mixed IDC/ILC cases were molecularly classified as ILC-like and IDC-like revealing no true hybrid features. This multidimensional molecular atlas sheds new light on the genetic bases of ILC and provides potential clinical options.

Published
2015

17. Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas

Author

Brat, Daniel J, Verhaak, Roel GW, Aldape, Kenneth D, Yung, WK Alfred, Salama, Sofie R, Cooper, Lee AD, Rheinbay, Esther, Miller, C Ryan, Vitucci, Mark, Morozova, Olena, Robertson, A Gordon, Noushmehr, Houtan, Laird, Peter W, Cherniack, Andrew D, Akbani, Rehan, Huse, Jason T, Ciriello, Giovanni, Poisson, Laila M, Barnholtz-Sloan, Jill S, Berger, Mitchel S, Brennan, Cameron, Colen, Rivka R, Colman, Howard, Flanders, Adam E, Giannini, Caterina, Grifford, Mia, Iavarone, Antonio, Jain, Rajan, Joseph, Isaac, Kim, Jaegil, Kasaian, Katayoon, Mikkelsen, Tom, Murray, Bradley A, O'Neill, Brian Patrick, Pachter, Lior, Parsons, Donald W, Sougnez, Carrie, Sulman, Erik P, Vandenberg, Scott R, Van Meir, Erwin G, von Deimling, Andreas, Zhang, Hailei, Crain, Daniel, Lau, Kevin, Mallery, David, Morris, Scott, Paulauskis, Joseph, Penny, Robert, Shelton, Troy, Sherman, Mark, Yena, Peggy, Black, Aaron, Bowen, Jay, Dicostanzo, Katie, Gastier-Foster, Julie, Leraas, Kristen M, Lichtenberg, Tara M, Pierson, Christopher R, Ramirez, Nilsa C, Taylor, Cynthia, Weaver, Stephanie, Wise, Lisa, Zmuda, Erik, Davidsen, Tanja, Demchok, John A, Eley, Greg, Ferguson, Martin L, Hutter, Carolyn M, Mills Shaw, Kenna R, Ozenberger, Bradley A, Sheth, Margi, Sofia, Heidi J, Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Zenklusen, Jean Claude, Ayala, Brenda, Baboud, Julien, Chudamani, Sudha, Jensen, Mark A, Liu, Jia, Pihl, Todd, Raman, Rohini, Wan, Yunhu, Wu, Ye, Ally, Adrian, Auman, J Todd, Balasundaram, Miruna, Balu, Saianand, Baylin, Stephen B, Beroukhim, Rameen, Bootwalla, Moiz S, Bowlby, Reanne, Bristow, Christopher A, Brooks, Denise, Butterfield, Yaron, Carlsen, Rebecca, Carter, Scott, Chin, Lynda, and Chu, Andy

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Clinical Research, Human Genome, Brain Cancer, Rare Diseases, Neurosciences, Biotechnology, Cancer Genomics, Genetics, Cancer, Brain Disorders, Adolescent, Adult, Aged, Chromosomes, Human, Pair 1, Chromosomes, Human, Pair 19, Cluster Analysis, DNA, Neoplasm, Female, Genes, p53, Glioblastoma, Glioma, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Mutation, Neoplasm Grading, Proportional Hazards Models, Sequence Analysis, DNA, Signal Transduction, Cancer Genome Atlas Research Network, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundDiffuse low-grade and intermediate-grade gliomas (which together make up the lower-grade gliomas, World Health Organization grades II and III) have highly variable clinical behavior that is not adequately predicted on the basis of histologic class. Some are indolent; others quickly progress to glioblastoma. The uncertainty is compounded by interobserver variability in histologic diagnosis. Mutations in IDH, TP53, and ATRX and codeletion of chromosome arms 1p and 19q (1p/19q codeletion) have been implicated as clinically relevant markers of lower-grade gliomas.MethodsWe performed genomewide analyses of 293 lower-grade gliomas from adults, incorporating exome sequence, DNA copy number, DNA methylation, messenger RNA expression, microRNA expression, and targeted protein expression. These data were integrated and tested for correlation with clinical outcomes.ResultsUnsupervised clustering of mutations and data from RNA, DNA-copy-number, and DNA-methylation platforms uncovered concordant classification of three robust, nonoverlapping, prognostically significant subtypes of lower-grade glioma that were captured more accurately by IDH, 1p/19q, and TP53 status than by histologic class. Patients who had lower-grade gliomas with an IDH mutation and 1p/19q codeletion had the most favorable clinical outcomes. Their gliomas harbored mutations in CIC, FUBP1, NOTCH1, and the TERT promoter. Nearly all lower-grade gliomas with IDH mutations and no 1p/19q codeletion had mutations in TP53 (94%) and ATRX inactivation (86%). The large majority of lower-grade gliomas without an IDH mutation had genomic aberrations and clinical behavior strikingly similar to those found in primary glioblastoma.ConclusionsThe integration of genomewide data from multiple platforms delineated three molecular classes of lower-grade gliomas that were more concordant with IDH, 1p/19q, and TP53 status than with histologic class. Lower-grade gliomas with an IDH mutation either had 1p/19q codeletion or carried a TP53 mutation. Most lower-grade gliomas without an IDH mutation were molecularly and clinically similar to glioblastoma. (Funded by the National Institutes of Health.).

Published
2015

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, Human Genome, Biotechnology, 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. Comprehensive genomic characterization of head and neck squamous cell carcinomas

Author

Lawrence, Michael S, Sougnez, Carrie, Lichtenstein, Lee, Cibulskis, Kristian, Lander, Eric, Gabriel, Stacey B, Getz, Gad, Ally, Adrian, Balasundaram, Miruna, Birol, Inanc, Bowlby, Reanne, Brooks, Denise, Butterfield, Yaron SN, Carlsen, Rebecca, Cheng, Dean, Chu, Andy, Dhalla, Noreen, Guin, Ranabir, Holt, Robert A, Jones, Steven JM, Lee, Darlene, Li, Haiyan I, Marra, Marco A, Mayo, Michael, Moore, Richard A, Mungall, Andrew J, Gordon Robertson, A, Schein, Jacqueline E, Sipahimalani, Payal, Tam, Angela, Thiessen, Nina, Wong, Tina, Protopopov, Alexei, Santoso, Netty, Lee, Semin, Parfenov, Michael, Zhang, Jianhua, Mahadeshwar, Harshad S, Tang, Jiabin, Ren, Xiaojia, Seth, Sahil, Haseley, Psalm, Zeng, Dong, Yang, Lixing, Xu, Andrew W, Song, Xingzhi, Pantazi, Angeliki, Bristow, Christopher A, Hadjipanayis, Angela, Seidman, Jonathan, Chin, Lynda, Park, Peter J, Kucherlapati, Raju, Akbani, Rehan, Casasent, Tod, Liu, Wenbin, Lu, Yiling, Mills, Gordon, Motter, Thomas, Weinstein, John, Diao, Lixia, Wang, Jing, Hong Fan, You, Liu, Jinze, Wang, Kai, Todd Auman, J, Balu, Saianand, Bodenheimer, Thomas, Buda, Elizabeth, Neil Hayes, D, Hoadley, Katherine A, Hoyle, Alan P, Jefferys, Stuart R, Jones, Corbin D, Kimes, Patrick K, Liu, Yufeng, Marron, JS, Meng, Shaowu, Mieczkowski, Piotr A, Mose, Lisle E, Parker, Joel S, Perou, Charles M, Prins, Jan F, Roach, Jeffrey, Shi, Yan, Simons, Janae V, Singh, Darshan, Soloway, Matthew G, Tan, Donghui, Veluvolu, Umadevi, Walter, Vonn, Waring, Scot, Wilkerson, Matthew D, Wu, Junyuan, Zhao, Ni, Cherniack, Andrew D, Hammerman, Peter S, Tward, Aaron D, Sekhar Pedamallu, Chandra, and Saksena, Gordon

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Oncology and Carcinogenesis, Human Genome, Biotechnology, Dental/Oral and Craniofacial Disease, Cancer, 2.1 Biological and endogenous factors, Aetiology, Good Health and Well Being, Carcinoma, Squamous Cell, DNA Copy Number Variations, DNA, Neoplasm, Female, Gene Expression Regulation, Neoplastic, Genome, Human, Genomics, Head and Neck Neoplasms, Humans, Male, Molecular Targeted Therapy, Mutation, Oncogenes, RNA, Neoplasm, Signal Transduction, Squamous Cell Carcinoma of Head and Neck, Transcription Factors, Cancer Genome Atlas Network, General Science & Technology
Abstract

The Cancer Genome Atlas profiled 279 head and neck squamous cell carcinomas (HNSCCs) to provide a comprehensive landscape of somatic genomic alterations. Here we show that human-papillomavirus-associated tumours are dominated by helical domain mutations of the oncogene PIK3CA, novel alterations involving loss of TRAF3, and amplification of the cell cycle gene E2F1. Smoking-related HNSCCs demonstrate near universal loss-of-function TP53 mutations and CDKN2A inactivation with frequent copy number alterations including amplification of 3q26/28 and 11q13/22. A subgroup of oral cavity tumours with favourable clinical outcomes displayed infrequent copy number alterations in conjunction with activating mutations of HRAS or PIK3CA, coupled with inactivating mutations of CASP8, NOTCH1 and TP53. Other distinct subgroups contained loss-of-function alterations of the chromatin modifier NSD1, WNT pathway genes AJUBA and FAT1, and activation of oxidative stress factor NFE2L2, mainly in laryngeal tumours. Therapeutic candidate alterations were identified in most HNSCCs.

Published
2015

20. Characterization of HPV and host genome interactions in primary head and neck cancers

Author

Parfenov, Michael, Pedamallu, Chandra Sekhar, Gehlenborg, Nils, Freeman, Samuel S, Danilova, Ludmila, Bristow, Christopher A, Lee, Semin, Hadjipanayis, Angela G, Ivanova, Elena V, Wilkerson, Matthew D, Protopopov, Alexei, Yang, Lixing, Seth, Sahil, Song, Xingzhi, Tang, Jiabin, Ren, Xiaojia, Zhang, Jianhua, Pantazi, Angeliki, Santoso, Netty, Xu, Andrew W, Mahadeshwar, Harshad, Wheeler, David A, Haddad, Robert I, Jung, Joonil, Ojesina, Akinyemi I, Issaeva, Natalia, Yarbrough, Wendell G, Hayes, D Neil, Grandis, Jennifer R, El-Naggar, Adel K, Meyerson, Matthew, Park, Peter J, Chin, Lynda, Seidman, JG, Hammerman, Peter S, Kucherlapati, Raju, Ally, Adrian, Balasundaram, Miruna, Birol, Inanc, Bowlby, Reanne, Butterfield, Yaron SN, Carlsen, Rebecca, Cheng, Dean, Chu, Andy, Dhalla, Noreen, Guin, Ranabir, Holt, Robert A, Jones, Steven JM, Lee, Darlene, Li, Haiyan I, Marra, Marco A, Mayo, Michael, Moore, Richard A, Mungall, Andrew J, Robertson, A Gordon, Schein, Jacqueline E, Sipahimalani, Payal, Tam, Angela, Thiessen, Nina, Wong, Tina, Mahadeshwar, Harshad S, Haseley, Psalm, Zeng, Dong, Bristow, Christopher, Hadjipanayis, Angela, Seidman, Jonathan, Akbani, Rehan, Casasent, Tod, Liu, Wenbin, Lu, Yiling, Mills, Gordon, Motter, Thomas, Weinstein, John, Diao, Lixia, Wang, Jing, Fan, You Hong, Liu, Jinze, Wang, Kai, Auman, J Todd, Balu, Saianand, Bodenheimer, Tom, Buda, Elizabeth, Hoadley, Katherine A, and Hoyle, Alan P

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Bioinformatics and Computational Biology, Genetics, Oncology and Carcinogenesis, Rare Diseases, Human Genome, Sexually Transmitted Infections, Cervical Cancer, Infectious Diseases, Dental/Oral and Craniofacial Disease, HIV/AIDS, Cancer, 2.2 Factors relating to the physical environment, Aetiology, 2.1 Biological and endogenous factors, Infection, Base Sequence, DNA Methylation, Gene Expression Regulation, Neoplastic, Genes, Neoplasm, Genome, Human, Head and Neck Neoplasms, Host-Pathogen Interactions, Humans, Molecular Sequence Data, Papillomaviridae, Virus Integration, cancer, head and neck, papilloma virus, genome rearrangement, integration sites, Cancer Genome Atlas Network
Abstract

Previous studies have established that a subset of head and neck tumors contains human papillomavirus (HPV) sequences and that HPV-driven head and neck cancers display distinct biological and clinical features. HPV is known to drive cancer by the actions of the E6 and E7 oncoproteins, but the molecular architecture of HPV infection and its interaction with the host genome in head and neck cancers have not been comprehensively described. We profiled a cohort of 279 head and neck cancers with next generation RNA and DNA sequencing and show that 35 (12.5%) tumors displayed evidence of high-risk HPV types 16, 33, or 35. Twenty-five cases had integration of the viral genome into one or more locations in the human genome with statistical enrichment for genic regions. Integrations had a marked impact on the human genome and were associated with alterations in DNA copy number, mRNA transcript abundance and splicing, and both inter- and intrachromosomal rearrangements. Many of these events involved genes with documented roles in cancer. Cancers with integrated vs. nonintegrated HPV displayed different patterns of DNA methylation and both human and viral gene expressions. Together, these data provide insight into the mechanisms by which HPV interacts with the human genome beyond expression of viral oncoproteins and suggest that specific integration events are an integral component of viral oncogenesis.

Published
2014

21. Depletion of Carcinoma-Associated Fibroblasts and Fibrosis Induces Immunosuppression and Accelerates Pancreas Cancer with Reduced Survival

Author

Özdemir, Berna C, Pentcheva-Hoang, Tsvetelina, Carstens, Julienne L, Zheng, Xiaofeng, Wu, Chia-Chin, Simpson, Tyler R, Laklai, Hanane, Sugimoto, Hikaru, Kahlert, Christoph, Novitskiy, Sergey V, De Jesus-Acosta, Ana, Sharma, Padmanee, Heidari, Pedram, Mahmood, Umar, Chin, Lynda, Moses, Harold L, Weaver, Valerie M, Maitra, Anirban, Allison, James P, LeBleu, Valerie S, and Kalluri, Raghu

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Rare Diseases, Digestive Diseases, Pancreatic Cancer, Cancer, 2.1 Biological and endogenous factors, Aetiology, Animals, Carcinoma, Pancreatic Ductal, Disease Models, Animal, Fibroblasts, Fibrosis, Humans, Immune Tolerance, Mice, Mice, Transgenic, Pancreatic Neoplasms, Survival Analysis, Neurosciences, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is associated with marked fibrosis and stromal myofibroblasts, but their functional contribution remains unknown. Transgenic mice with the ability to delete αSMA(+) myofibroblasts in pancreatic cancer were generated. Depletion starting at either noninvasive precursor (pancreatic intraepithelial neoplasia) or the PDAC stage led to invasive, undifferentiated tumors with enhanced hypoxia, epithelial-to-mesenchymal transition, and cancer stem cells, with diminished animal survival. In PDAC patients, fewer myofibroblasts in their tumors also correlated with reduced survival. Suppressed immune surveillance with increased CD4(+)Foxp3(+) Tregs was observed in myofibroblast-depleted mouse tumors. Although myofibroblast-depleted tumors did not respond to gemcitabine, anti-CTLA4 immunotherapy reversed disease acceleration and prolonged animal survival. This study underscores the need for caution in targeting carcinoma-associated fibroblasts in PDAC.

Published
2014

22. Double Minute Chromosomes in Glioblastoma Multiforme Are Revealed by Precise Reconstruction of Oncogenic Amplicons

Author

Sanborn, J Zachary, Salama, Sofie R, Grifford, Mia, Brennan, Cameron W, Mikkelsen, Tom, Jhanwar, Suresh, Katzman, Sol, Chin, Lynda, and Haussler, David

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Bioinformatics and Computational Biology, Genetics, Oncology and Carcinogenesis, Cancer, Human Genome, Brain Disorders, Brain Cancer, Biotechnology, Rare Diseases, Pediatric Research Initiative, Aetiology, 2.1 Biological and endogenous factors, Biomarkers, Tumor, Brain, Brain Neoplasms, Case-Control Studies, Chromosome Aberrations, Chromosome Mapping, Chromosomes, Human, Cohort Studies, Gene Dosage, Genome, Human, Glioblastoma, Humans, In Situ Hybridization, Fluorescence, RNA, Messenger, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Sequence Analysis, DNA, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

DNA sequencing offers a powerful tool in oncology based on the precise definition of structural rearrangements and copy number in tumor genomes. Here, we describe the development of methods to compute copy number and detect structural variants to locally reconstruct highly rearranged regions of the tumor genome with high precision from standard, short-read, paired-end sequencing datasets. We find that circular assemblies are the most parsimonious explanation for a set of highly amplified tumor regions in a subset of glioblastoma multiforme samples sequenced by The Cancer Genome Atlas (TCGA) consortium, revealing evidence for double minute chromosomes in these tumors. Further, we find that some samples harbor multiple circular amplicons and, in some cases, further rearrangements occurred after the initial amplicon-generating event. Fluorescence in situ hybridization analysis offered an initial confirmation of the presence of double minute chromosomes. Gene content in these assemblies helps identify likely driver oncogenes for these amplicons. RNA-seq data available for one double minute chromosome offered additional support for our local tumor genome assemblies, and identified the birth of a novel exon made possible through rearranged sequences present in the double minute chromosomes. Our method was also useful for analysis of a larger set of glioblastoma multiforme tumors for which exome sequencing data are available, finding evidence for oncogenic double minute chromosomes in more than 20% of clinical specimens examined, a frequency consistent with previous estimates.

Published
2013

23. 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 Disorders, Cancer, Biotechnology, Cancer Genomics, Neurosciences, Precision Medicine, Human Genome, Brain Cancer, Orphan Drug, Rare Diseases, 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

24. PAF promotes stemness and radioresistance of glioma stem cells

Author

Ong, Derrick Sek Tong, Hu, Baoli, Ho, Yan Wing, Sauvé, Charles-Etienne Gabriel, Bristow, Christopher A., Wang, Qianghu, Multani, Asha S., Chen, Peiwen, Nezi, Luigi, Jiang, Shan, Gorman, Claire Elizabeth, Monasterio, Marta Moreno, Koul, Dimpy, Marchesini, Matteo, Colla, Simona, Jin, Eun-Jung, Sulman, Erik P., Spring, Denise J., Yung, Wai-Kwan Alfred, Verhaak, Roel G. W., Chin, Lynda, Wang, Y. Alan, and DePinho, Ronald A.

Published
2017

25. Integrated genomic characterization of endometrial carcinoma

Author

Getz, Gad, Gabriel, Stacey B, Cibulskis, Kristian, Lander, Eric, Sivachenko, Andrey, Sougnez, Carrie, Lawrence, Mike, Kandoth, Cyriac, Dooling, David, Fulton, Robert, Fulton, Lucinda, Kalicki-Veizer, Joelle, McLellan, Michael D, O’Laughlin, Michelle, Schmidt, Heather, Wilson, Richard K, Ye, Kai, Ding, Li, Mardis, Elaine R, Ally, Adrian, Balasundaram, Miruna, Birol, Inanc, Butterfield, Yaron SN, Carlsen, Rebecca, Carter, Candace, Chu, Andy, Chuah, Eric, Chun, Hye-Jung E, Dhalla, Noreen, Guin, Ranabir, Hirst, Carrie, Holt, Robert A, Jones, Steven JM, Lee, Darlene, Li, Haiyan I, Marra, Marco A, Mayo, Michael, Moore, Richard A, Mungall, Andrew J, Plettner, Patrick, Schein, Jacqueline E, Sipahimalani, Payal, Tam, Angela, Varhol, Richard J, Gordon Robertson, A, Cherniack, Andrew D, Pashtan, Itai, Saksena, Gordon, Onofrio, Robert C, Schumacher, Steven E, Tabak, Barbara, Carter, Scott L, Hernandez, Bryan, Gentry, Jeff, Salvesen, Helga B, Ardlie, Kristin, Winckler, Wendy, Beroukhim, Rameen, Meyerson, Matthew, Hadjipanayis, Angela, Lee, Semin, Mahadeshwar, Harshad S, Park, Peter, Protopopov, Alexei, Ren, Xiaojia, Seth, Sahil, Song, Xingzhi, Tang, Jiabin, Xi, Ruibin, Yang, Lixing, Zeng, Dong, Kucherlapati, Raju, Chin, Lynda, Zhang, Jianhua, Todd Auman, J, Balu, Saianand, Bodenheimer, Tom, Buda, Elizabeth, Neil Hayes, D, Hoyle, Alan P, Jefferys, Stuart R, Jones, Corbin D, Meng, Shaowu, Mieczkowski, Piotr A, Mose, Lisle E, Parker, Joel S, Perou, Charles M, Roach, Jeff, Shi, Yan, Simons, Janae V, Soloway, Mathew G, Tan, Donghui, Topal, Michael D, Waring, Scot, Wu, Junyuan, Hoadley, Katherine A, Baylin, Stephen B, and Bootwalla, Moiz S

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Oncology and Carcinogenesis, Reproductive Medicine, Human Genome, Cancer, Uterine Cancer, Biotechnology, Breast Neoplasms, Chromosome Aberrations, DNA Copy Number Variations, DNA Mutational Analysis, DNA Polymerase II, DNA-Binding Proteins, Endometrial Neoplasms, Exome, Female, Gene Expression Regulation, Neoplastic, Genome, Human, Genomics, Humans, Ovarian Neoplasms, Poly-ADP-Ribose Binding Proteins, Signal Transduction, Transcription Factors, Cancer Genome Atlas Research Network, General Science & Technology
Abstract

We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine serous tumours and ∼25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, and frequent TP53 mutations. Most endometrioid tumours had few copy number alterations or TP53 mutations, but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A and KRAS and novel mutations in the SWI/SNF chromatin remodelling complex gene ARID5B. A subset of endometrioid tumours that we identified had a markedly increased transversion mutation frequency and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours.

Published
2013

26. Comprehensive genomic characterization of squamous cell lung cancers

Author

Hammerman, Peter S, Lawrence, Michael S, Voet, Douglas, Jing, Rui, Cibulskis, Kristian, Sivachenko, Andrey, Stojanov, Petar, McKenna, Aaron, Lander, Eric S, Gabriel, Stacey, Getz, Gad, Sougnez, Carrie, Imielinski, Marcin, Helman, Elena, Hernandez, Bryan, Pho, Nam H, Meyerson, Matthew, Chu, Andy, Chun, Hye-Jung E, Mungall, Andrew J, Pleasance, Erin, Gordon Robertson, A, Sipahimalani, Payal, Stoll, Dominik, Balasundaram, Miruna, Birol, Inanc, Butterfield, Yaron SN, Chuah, Eric, Coope, Robin JN, Corbett, Richard, Dhalla, Noreen, Guin, Ranabir, He, An, Hirst, Carrie, Hirst, Martin, Holt, Robert A, Lee, Darlene, Li, Haiyan I, Mayo, Michael, Moore, Richard A, Mungall, Karen, Ming Nip, Ka, Olshen, Adam, Schein, Jacqueline E, Slobodan, Jared R, Tam, Angela, Thiessen, Nina, Varhol, Richard, Zeng, Thomas, Zhao, Yongjun, Jones, Steven JM, Marra, Marco A, Saksena, Gordon, Cherniack, Andrew D, Schumacher, Stephen E, Tabak, Barbara, Carter, Scott L, Nguyen, Huy, Onofrio, Robert C, Crenshaw, Andrew, Ardlie, Kristin, Beroukhim, Rameen, Winckler, Wendy, Protopopov, Alexei, Zhang, Jianhua, Hadjipanayis, Angela, Lee, Semin, Xi, Ruibin, Yang, Lixing, Ren, Xiaojia, Zhang, Hailei, Shukla, Sachet, Chen, Peng-Chieh, Haseley, Psalm, Lee, Eunjung, Chin, Lynda, Park, Peter J, Kucherlapati, Raju, Socci, Nicholas D, Liang, Yupu, Schultz, Nikolaus, Borsu, Laetitia, Lash, Alex E, Viale, Agnes, Sander, Chris, Ladanyi, Marc, Todd Auman, J, Hoadley, Katherine A, Wilkerson, Matthew D, Shi, Yan, Liquori, Christina, Meng, Shaowu, Li, Ling, Turman, Yidi J, Topal, Michael D, and Tan, Donghui

Subjects
Human Genome, Biotechnology, Genetics, Rare Diseases, Cancer, Lung Cancer, Lung, Aetiology, 2.1 Biological and endogenous factors, Adenocarcinoma, Adenocarcinoma of Lung, Carcinoma, Squamous Cell, DNA Mutational Analysis, Gene Deletion, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Genes, p16, Genes, p53, Genome, Human, Genomics, Humans, Lung Neoplasms, Molecular Targeted Therapy, Mutation, Mutation Rate, Phosphatidylinositol 3-Kinases, Signal Transduction, Cancer Genome Atlas Research Network, General Science & Technology
Abstract

Lung squamous cell carcinoma is a common type of lung cancer, causing approximately 400,000 deaths per year worldwide. Genomic alterations in squamous cell lung cancers have not been comprehensively characterized, and no molecularly targeted agents have been specifically developed for its treatment. As part of The Cancer Genome Atlas, here we profile 178 lung squamous cell carcinomas to provide a comprehensive landscape of genomic and epigenomic alterations. We show that the tumour type is characterized by complex genomic alterations, with a mean of 360 exonic mutations, 165 genomic rearrangements, and 323 segments of copy number alteration per tumour. We find statistically recurrent mutations in 11 genes, including mutation of TP53 in nearly all specimens. Previously unreported loss-of-function mutations are seen in the HLA-A class I major histocompatibility gene. Significantly altered pathways included NFE2L2 and KEAP1 in 34%, squamous differentiation genes in 44%, phosphatidylinositol-3-OH kinase pathway genes in 47%, and CDKN2A and RB1 in 72% of tumours. We identified a potential therapeutic target in most tumours, offering new avenues of investigation for the treatment of squamous cell lung cancers.

Published
2012

27. High-Resolution Genomic Profiles of Human Lung Cancer

Author

Tonon, Giovanni, Wong, Kwok-Kin, Maulik, Gautam, Brennan, Cameron, Feng, Bin, Zhang, Yunyu, Khatry, Deepak B., Protopopov, Alexei, You, Mingjian James, Aguirre, Andrew J., Martin, Eric S., Yang, Zhaohui, Ji, Hongbin, Chin, Lynda, DePinho, Ronald A., and Cavenee, Webster K.

Published
2005

28. International network of cancer genome projects

Author

Hudson (Chairperson), Thomas J, Anderson, Warwick, Aretz, Axel, Barker, Anna D, Bell, Cindy, Bernabé, Rosa R, Bhan, MK, Calvo, Fabien, Eerola, Iiro, Gerhard, Daniela S, Guttmacher, Alan, Guyer, Mark, Hemsley, Fiona M, Jennings, Jennifer L, Kerr, David, Klatt, Peter, Kolar, Patrik, Kusuda, Jun, Lane, David P, Laplace, Frank, Lu, Youyong, Nettekoven, Gerd, Ozenberger, Brad, Peterson, Jane, Rao, TS, Remacle, Jacques, Schafer, Alan J, Shibata, Tatsuhiro, Stratton, Michael R, Vockley, Joseph G, Watanabe, Koichi, Yang, Huanming, Yuen, Matthew MF, Knoppers (Leader), Bartha M, Bobrow, Martin, Cambon-Thomsen, Anne, Dressler, Lynn G, Dyke, Stephanie OM, Joly, Yann, Kato, Kazuto, Kennedy, Karen L, Nicolás, Pilar, Parker, Michael J, Rial-Sebbag, Emmanuelle, Romeo-Casabona, Carlos M, Shaw, Kenna M, Wallace, Susan, Wiesner, Georgia L, Zeps, Nikolajs, Lichter (Leader), Peter, Biankin, Andrew V, Chabannon, Christian, Chin, Lynda, Clément, Bruno, de Alava, Enrique, Degos, Françoise, Ferguson, Martin L, Geary, Peter, Hayes, D Neil, Hudson, Thomas J, Johns, Amber L, Kasprzyk, Arek, Nakagawa, Hidewaki, Penny, Robert, Piris, Miguel A, Sarin, Rajiv, Scarpa, Aldo, van de Vijver, Marc, Futreal (Leader), P Andrew, Aburatani, Hiroyuki, Bayés, Mónica, Bowtell, David DL, Campbell, Peter J, Estivill, Xavier, Grimmond, Sean M, Gut, Ivo, Hirst, Martin, López-Otín, Carlos, Majumder, Partha, Marra, Marco, McPherson, John D, Ning, Zemin, Puente, Xose S, Ruan, Yijun, Stunnenberg, Hendrik G, Swerdlow, Harold, Velculescu, Victor E, Wilson, Richard K, Xue, Hong H, Yang, Liu, Spellman (Leader), Paul T, Bader, Gary D, Boutros, Paul C, and Flicek, Paul

Subjects
Cancer, Genetics, Human Genome, DNA Methylation, DNA Mutational Analysis, Databases, Genetic, Genes, Neoplasm, Genetics, Medical, Genome, Human, Genomics, Humans, Intellectual Property, International Cooperation, Mutation, Neoplasms, International Cancer Genome Consortium, General Science & Technology
Abstract

The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.

Published
2010

29. International network of cancer genome projects.

Author

International Cancer Genome Consortium, Hudson, Thomas J, Anderson, Warwick, Artez, Axel, Barker, Anna D, Bell, Cindy, Bernabé, Rosa R, Bhan, MK, Calvo, Fabien, Eerola, Iiro, Gerhard, Daniela S, Guttmacher, Alan, Guyer, Mark, Hemsley, Fiona M, Jennings, Jennifer L, Kerr, David, Klatt, Peter, Kolar, Patrik, Kusada, Jun, Lane, David P, Laplace, Frank, Youyong, Lu, Nettekoven, Gerd, Ozenberger, Brad, Peterson, Jane, Rao, TS, Remacle, Jacques, Schafer, Alan J, Shibata, Tatsuhiro, Stratton, Michael R, Vockley, Joseph G, Watanabe, Koichi, Yang, Huanming, Yuen, Matthew MF, Knoppers, Bartha M, Bobrow, Martin, Cambon-Thomsen, Anne, Dressler, Lynn G, Dyke, Stephanie OM, Joly, Yann, Kato, Kazuto, Kennedy, Karen L, Nicolás, Pilar, Parker, Michael J, Rial-Sebbag, Emmanuelle, Romeo-Casabona, Carlos M, Shaw, Kenna M, Wallace, Susan, Wiesner, Georgia L, Zeps, Nikolajs, Lichter, Peter, Biankin, Andrew V, Chabannon, Christian, Chin, Lynda, Clément, Bruno, de Alava, Enrique, Degos, Françoise, Ferguson, Martin L, Geary, Peter, Hayes, D Neil, Johns, Amber L, Kasprzyk, Arek, Nakagawa, Hidewaki, Penny, Robert, Piris, Miguel A, Sarin, Rajiv, Scarpa, Aldo, van de Vijver, Marc, Futreal, P Andrew, Aburatani, Hiroyuki, Bayés, Mónica, Botwell, David DL, Campbell, Peter J, Estivill, Xavier, Grimmond, Sean M, Gut, Ivo, Hirst, Martin, López-Otín, Carlos, Majumder, Partha, Marra, Marco, McPherson, John D, Ning, Zemin, Puente, Xose S, Ruan, Yijun, Stunnenberg, Hendrik G, Swerdlow, Harold, Velculescu, Victor E, Wilson, Richard K, Xue, Hong H, Yang, Liu, Spellman, Paul T, Bader, Gary D, and Boutros, Paul C

Subjects
International Cancer Genome Consortium, Humans, Neoplasms, DNA Mutational Analysis, Genetics, Medical, Genomics, DNA Methylation, Mutation, Genome, Human, International Cooperation, Intellectual Property, Databases, Genetic, Genes, Neoplasm, Genetics, Medical, Genome, Human, Databases, Genetic, Genes, Neoplasm, General Science & Technology
Abstract

The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.

Published
2010

31. High-Resolution Characterization of the Pancreatic Adenocarcinoma Genome

Author

Aguirre, Andrew J., Brennan, Cameron, Bailey, Gerald, Sinha, Raktim, Feng, Bin, Leo, Christopher, Zhang, Yunyu, Zhang, Jean, Gans, Joseph D., Bardeesy, Nabeel, Cauwels, Craig, Cordon-Cardo, Carlos, Redston, Mark S., DePinho, Ronald A., Chin, Lynda, and Cantley, Lewis C.

Published
2004

32. Data from Biomarker Accessible and Chemically Addressable Mechanistic Subtypes of BRAF Melanoma

Author

Eskiocak, Banu, primary, McMillan, Elizabeth A., primary, Mendiratta, Saurabh, primary, Kollipara, Rahul K., primary, Zhang, Hailei, primary, Humphries, Caroline G., primary, Wang, Changguang, primary, Garcia-Rodriguez, Jose, primary, Ding, Ming, primary, Zaman, Aubhishek, primary, Rosales, Tracy I., primary, Eskiocak, Ugur, primary, Smith, Michael P., primary, Sudderth, Jessica, primary, Komurov, Kakajan, primary, Deberardinis, Ralph J., primary, Wellbrock, Claudia, primary, Davies, Michael A., primary, Wargo, Jennifer A., primary, Yu, Yonghao, primary, De Brabander, Jef K., primary, Williams, Noelle S., primary, Chin, Lynda, primary, Rizos, Helen, primary, Long, Georgina V., primary, Kittler, Ralf, primary, and White, Michael A., primary

Published
2023
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33. Data from Targeting YAP-Dependent MDSC Infiltration Impairs Tumor Progression

Author

Wang, Guocan, primary, Lu, Xin, primary, Dey, Prasenjit, primary, Deng, Pingna, primary, Wu, Chia Chin, primary, Jiang, Shan, primary, Fang, Zhuangna, primary, Zhao, Kun, primary, Konaparthi, Ramakrishna, primary, Hua, Sujun, primary, Zhang, Jianhua, primary, Li-Ning-Tapia, Elsa M., primary, Kapoor, Avnish, primary, Wu, Chang-Jiun, primary, Patel, Neelay Bhaskar, primary, Guo, Zhenglin, primary, Ramamoorthy, Vandhana, primary, Tieu, Trang N., primary, Heffernan, Tim, primary, Zhao, Di, primary, Shang, Xiaoying, primary, Khadka, Sunada, primary, Hou, Pingping, primary, Hu, Baoli, primary, Jin, Eun-Jung, primary, Yao, Wantong, primary, Pan, Xiaolu, primary, Ding, Zhihu, primary, Shi, Yanxia, primary, Li, Liren, primary, Chang, Qing, primary, Troncoso, Patricia, primary, Logothetis, Christopher J., primary, McArthur, Mark J., primary, Chin, Lynda, primary, Wang, Y. Alan, primary, and DePinho, Ronald A., primary

Published
2023
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34. Supplementary Figure Legends from Analysis of Immune Signatures in Longitudinal Tumor Samples Yields Insight into Biomarkers of Response and Mechanisms of Resistance to Immune Checkpoint Blockade

Author

Chen, Pei-Ling, primary, Roh, Whijae, primary, Reuben, Alexandre, primary, Cooper, Zachary A., primary, Spencer, Christine N., primary, Prieto, Peter A., primary, Miller, John P., primary, Bassett, Roland L., primary, Gopalakrishnan, Vancheswaran, primary, Wani, Khalida, primary, De Macedo, Mariana Petaccia, primary, Austin-Breneman, Jacob L., primary, Jiang, Hong, primary, Chang, Qing, primary, Reddy, Sangeetha M., primary, Chen, Wei-Shen, primary, Tetzlaff, Michael T., primary, Broaddus, Russell J., primary, Davies, Michael A., primary, Gershenwald, Jeffrey E., primary, Haydu, Lauren, primary, Lazar, Alexander J., primary, Patel, Sapna P., primary, Hwu, Patrick, primary, Hwu, Wen-Jen, primary, Diab, Adi, primary, Glitza, Isabella C., primary, Woodman, Scott E., primary, Vence, Luis M., primary, Wistuba, Ignacio I., primary, Amaria, Rodabe N., primary, Kwong, Lawrence N., primary, Prieto, Victor, primary, Davis, R. Eric, primary, Ma, Wencai, primary, Overwijk, Willem W., primary, Sharpe, Arlene H., primary, Hu, Jianhua, primary, Futreal, P. Andrew, primary, Blando, Jorge, primary, Sharma, Padmanee, primary, Allison, James P., primary, Chin, Lynda, primary, and Wargo, Jennifer A., primary

Published
2023
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35. Supplementary Tables S1-S15 from Biomarker Accessible and Chemically Addressable Mechanistic Subtypes of BRAF Melanoma

Author

Eskiocak, Banu, primary, McMillan, Elizabeth A., primary, Mendiratta, Saurabh, primary, Kollipara, Rahul K., primary, Zhang, Hailei, primary, Humphries, Caroline G., primary, Wang, Changguang, primary, Garcia-Rodriguez, Jose, primary, Ding, Ming, primary, Zaman, Aubhishek, primary, Rosales, Tracy I., primary, Eskiocak, Ugur, primary, Smith, Michael P., primary, Sudderth, Jessica, primary, Komurov, Kakajan, primary, Deberardinis, Ralph J., primary, Wellbrock, Claudia, primary, Davies, Michael A., primary, Wargo, Jennifer A., primary, Yu, Yonghao, primary, De Brabander, Jef K., primary, Williams, Noelle S., primary, Chin, Lynda, primary, Rizos, Helen, primary, Long, Georgina V., primary, Kittler, Ralf, primary, and White, Michael A., primary

Published
2023
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36. Supplementary Tables 1 - 11 from Analysis of Immune Signatures in Longitudinal Tumor Samples Yields Insight into Biomarkers of Response and Mechanisms of Resistance to Immune Checkpoint Blockade

Author

Chen, Pei-Ling, primary, Roh, Whijae, primary, Reuben, Alexandre, primary, Cooper, Zachary A., primary, Spencer, Christine N., primary, Prieto, Peter A., primary, Miller, John P., primary, Bassett, Roland L., primary, Gopalakrishnan, Vancheswaran, primary, Wani, Khalida, primary, De Macedo, Mariana Petaccia, primary, Austin-Breneman, Jacob L., primary, Jiang, Hong, primary, Chang, Qing, primary, Reddy, Sangeetha M., primary, Chen, Wei-Shen, primary, Tetzlaff, Michael T., primary, Broaddus, Russell J., primary, Davies, Michael A., primary, Gershenwald, Jeffrey E., primary, Haydu, Lauren, primary, Lazar, Alexander J., primary, Patel, Sapna P., primary, Hwu, Patrick, primary, Hwu, Wen-Jen, primary, Diab, Adi, primary, Glitza, Isabella C., primary, Woodman, Scott E., primary, Vence, Luis M., primary, Wistuba, Ignacio I., primary, Amaria, Rodabe N., primary, Kwong, Lawrence N., primary, Prieto, Victor, primary, Davis, R. Eric, primary, Ma, Wencai, primary, Overwijk, Willem W., primary, Sharpe, Arlene H., primary, Hu, Jianhua, primary, Futreal, P. Andrew, primary, Blando, Jorge, primary, Sharma, Padmanee, primary, Allison, James P., primary, Chin, Lynda, primary, and Wargo, Jennifer A., primary

Published
2023
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37. Supplementary Methods, Figure Legends, Figures S1 - S7 from Targeting YAP-Dependent MDSC Infiltration Impairs Tumor Progression

Author

Wang, Guocan, primary, Lu, Xin, primary, Dey, Prasenjit, primary, Deng, Pingna, primary, Wu, Chia Chin, primary, Jiang, Shan, primary, Fang, Zhuangna, primary, Zhao, Kun, primary, Konaparthi, Ramakrishna, primary, Hua, Sujun, primary, Zhang, Jianhua, primary, Li-Ning-Tapia, Elsa M., primary, Kapoor, Avnish, primary, Wu, Chang-Jiun, primary, Patel, Neelay Bhaskar, primary, Guo, Zhenglin, primary, Ramamoorthy, Vandhana, primary, Tieu, Trang N., primary, Heffernan, Tim, primary, Zhao, Di, primary, Shang, Xiaoying, primary, Khadka, Sunada, primary, Hou, Pingping, primary, Hu, Baoli, primary, Jin, Eun-Jung, primary, Yao, Wantong, primary, Pan, Xiaolu, primary, Ding, Zhihu, primary, Shi, Yanxia, primary, Li, Liren, primary, Chang, Qing, primary, Troncoso, Patricia, primary, Logothetis, Christopher J., primary, McArthur, Mark J., primary, Chin, Lynda, primary, Wang, Y. Alan, primary, and DePinho, Ronald A., primary

Published
2023
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38. Supplementary Text, Figure Legends, Figures S1-S12 from Biomarker Accessible and Chemically Addressable Mechanistic Subtypes of BRAF Melanoma

Author

Eskiocak, Banu, primary, McMillan, Elizabeth A., primary, Mendiratta, Saurabh, primary, Kollipara, Rahul K., primary, Zhang, Hailei, primary, Humphries, Caroline G., primary, Wang, Changguang, primary, Garcia-Rodriguez, Jose, primary, Ding, Ming, primary, Zaman, Aubhishek, primary, Rosales, Tracy I., primary, Eskiocak, Ugur, primary, Smith, Michael P., primary, Sudderth, Jessica, primary, Komurov, Kakajan, primary, Deberardinis, Ralph J., primary, Wellbrock, Claudia, primary, Davies, Michael A., primary, Wargo, Jennifer A., primary, Yu, Yonghao, primary, De Brabander, Jef K., primary, Williams, Noelle S., primary, Chin, Lynda, primary, Rizos, Helen, primary, Long, Georgina V., primary, Kittler, Ralf, primary, and White, Michael A., primary

Published
2023
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39. 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
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40. 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
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41. Supplementary Methods from Biomarker Accessible and Chemically Addressable Mechanistic Subtypes of BRAF Melanoma

Author

Eskiocak, Banu, primary, McMillan, Elizabeth A., primary, Mendiratta, Saurabh, primary, Kollipara, Rahul K., primary, Zhang, Hailei, primary, Humphries, Caroline G., primary, Wang, Changguang, primary, Garcia-Rodriguez, Jose, primary, Ding, Ming, primary, Zaman, Aubhishek, primary, Rosales, Tracy I., primary, Eskiocak, Ugur, primary, Smith, Michael P., primary, Sudderth, Jessica, primary, Komurov, Kakajan, primary, Deberardinis, Ralph J., primary, Wellbrock, Claudia, primary, Davies, Michael A., primary, Wargo, Jennifer A., primary, Yu, Yonghao, primary, De Brabander, Jef K., primary, Williams, Noelle S., primary, Chin, Lynda, primary, Rizos, Helen, primary, Long, Georgina V., primary, Kittler, Ralf, primary, and White, Michael A., primary

Published
2023
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42. Supplementary Table 1 from Dual Roles of RNF2 in Melanoma Progression

Author

Rai, Kunal, primary, Akdemir, Kadir C., primary, Kwong, Lawrence N., primary, Fiziev, Petko, primary, Wu, Chang-Jiun, primary, Keung, Emily Z., primary, Sharma, Sneha, primary, Samant, Neha S., primary, Williams, Maura, primary, Axelrad, Jacob B., primary, Shah, Amiksha, primary, Yang, Dong, primary, Grimm, Elizabeth A., primary, Barton, Michelle C., primary, Milton, Denai R., primary, Heffernan, Timothy P., primary, Horner, James W., primary, Ekmekcioglu, Suhendan, primary, Lazar, Alexander J., primary, Ernst, Jason, primary, and Chin, Lynda, primary

Published
2023
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43. Supplementary Tables 1-2, Figures 1-8 from PTEN Is a Major Tumor Suppressor in Pancreatic Ductal Adenocarcinoma and Regulates an NF-κB–Cytokine Network

Author

Ying, Haoqiang, primary, Elpek, Kutlu G., primary, Vinjamoori, Anant, primary, Zimmerman, Stephanie M., primary, Chu, Gerald C., primary, Yan, Haiyan, primary, Fletcher-Sananikone, Eliot, primary, Zhang, Hailei, primary, Liu, Yingchun, primary, Wang, Wei, primary, Ren, Xiaojia, primary, Zheng, Hongwu, primary, Kimmelman, Alec C., primary, Paik, Ji-hye, primary, Lim, Carol, primary, Perry, Samuel R., primary, Jiang, Shan, primary, Malinn, Brian, primary, Protopopov, Alexei, primary, Colla, Simona, primary, Xiao, Yonghong, primary, Hezel, Aram F., primary, Bardeesy, Nabeel, primary, Turley, Shannon J., primary, Wang, Y. Alan, primary, Chin, Lynda, primary, Thayer, Sarah P., primary, and DePinho, Ronald A., primary

Published
2023
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44. Supplementary Methods, Figure Legends, Table Legends from Dual Roles of RNF2 in Melanoma Progression

Author

Rai, Kunal, primary, Akdemir, Kadir C., primary, Kwong, Lawrence N., primary, Fiziev, Petko, primary, Wu, Chang-Jiun, primary, Keung, Emily Z., primary, Sharma, Sneha, primary, Samant, Neha S., primary, Williams, Maura, primary, Axelrad, Jacob B., primary, Shah, Amiksha, primary, Yang, Dong, primary, Grimm, Elizabeth A., primary, Barton, Michelle C., primary, Milton, Denai R., primary, Heffernan, Timothy P., primary, Horner, James W., primary, Ekmekcioglu, Suhendan, primary, Lazar, Alexander J., primary, Ernst, Jason, primary, and Chin, Lynda, primary

Published
2023
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45. Supplementary Table 3 from Dual Roles of RNF2 in Melanoma Progression

Author

Rai, Kunal, primary, Akdemir, Kadir C., primary, Kwong, Lawrence N., primary, Fiziev, Petko, primary, Wu, Chang-Jiun, primary, Keung, Emily Z., primary, Sharma, Sneha, primary, Samant, Neha S., primary, Williams, Maura, primary, Axelrad, Jacob B., primary, Shah, Amiksha, primary, Yang, Dong, primary, Grimm, Elizabeth A., primary, Barton, Michelle C., primary, Milton, Denai R., primary, Heffernan, Timothy P., primary, Horner, James W., primary, Ekmekcioglu, Suhendan, primary, Lazar, Alexander J., primary, Ernst, Jason, primary, and Chin, Lynda, primary

Published
2023
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46. Supplementary Table S7 from Targeting YAP-Dependent MDSC Infiltration Impairs Tumor Progression

Author

Wang, Guocan, primary, Lu, Xin, primary, Dey, Prasenjit, primary, Deng, Pingna, primary, Wu, Chia Chin, primary, Jiang, Shan, primary, Fang, Zhuangna, primary, Zhao, Kun, primary, Konaparthi, Ramakrishna, primary, Hua, Sujun, primary, Zhang, Jianhua, primary, Li-Ning-Tapia, Elsa M., primary, Kapoor, Avnish, primary, Wu, Chang-Jiun, primary, Patel, Neelay Bhaskar, primary, Guo, Zhenglin, primary, Ramamoorthy, Vandhana, primary, Tieu, Trang N., primary, Heffernan, Tim, primary, Zhao, Di, primary, Shang, Xiaoying, primary, Khadka, Sunada, primary, Hou, Pingping, primary, Hu, Baoli, primary, Jin, Eun-Jung, primary, Yao, Wantong, primary, Pan, Xiaolu, primary, Ding, Zhihu, primary, Shi, Yanxia, primary, Li, Liren, primary, Chang, Qing, primary, Troncoso, Patricia, primary, Logothetis, Christopher J., primary, McArthur, Mark J., primary, Chin, Lynda, primary, Wang, Y. Alan, primary, and DePinho, Ronald A., primary

Published
2023
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47. Supplementary Figures 1 - 13 from Analysis of Immune Signatures in Longitudinal Tumor Samples Yields Insight into Biomarkers of Response and Mechanisms of Resistance to Immune Checkpoint Blockade

Author

Chen, Pei-Ling, primary, Roh, Whijae, primary, Reuben, Alexandre, primary, Cooper, Zachary A., primary, Spencer, Christine N., primary, Prieto, Peter A., primary, Miller, John P., primary, Bassett, Roland L., primary, Gopalakrishnan, Vancheswaran, primary, Wani, Khalida, primary, De Macedo, Mariana Petaccia, primary, Austin-Breneman, Jacob L., primary, Jiang, Hong, primary, Chang, Qing, primary, Reddy, Sangeetha M., primary, Chen, Wei-Shen, primary, Tetzlaff, Michael T., primary, Broaddus, Russell J., primary, Davies, Michael A., primary, Gershenwald, Jeffrey E., primary, Haydu, Lauren, primary, Lazar, Alexander J., primary, Patel, Sapna P., primary, Hwu, Patrick, primary, Hwu, Wen-Jen, primary, Diab, Adi, primary, Glitza, Isabella C., primary, Woodman, Scott E., primary, Vence, Luis M., primary, Wistuba, Ignacio I., primary, Amaria, Rodabe N., primary, Kwong, Lawrence N., primary, Prieto, Victor, primary, Davis, R. Eric, primary, Ma, Wencai, primary, Overwijk, Willem W., primary, Sharpe, Arlene H., primary, Hu, Jianhua, primary, Futreal, P. Andrew, primary, Blando, Jorge, primary, Sharma, Padmanee, primary, Allison, James P., primary, Chin, Lynda, primary, and Wargo, Jennifer A., primary

Published
2023
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48. Supplementary Table 2 from Dual Roles of RNF2 in Melanoma Progression

Author

Rai, Kunal, primary, Akdemir, Kadir C., primary, Kwong, Lawrence N., primary, Fiziev, Petko, primary, Wu, Chang-Jiun, primary, Keung, Emily Z., primary, Sharma, Sneha, primary, Samant, Neha S., primary, Williams, Maura, primary, Axelrad, Jacob B., primary, Shah, Amiksha, primary, Yang, Dong, primary, Grimm, Elizabeth A., primary, Barton, Michelle C., primary, Milton, Denai R., primary, Heffernan, Timothy P., primary, Horner, James W., primary, Ekmekcioglu, Suhendan, primary, Lazar, Alexander J., primary, Ernst, Jason, primary, and Chin, Lynda, primary

Published
2023
Full Text
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49. 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
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50. Data from Dual Roles of RNF2 in Melanoma Progression

Author

Rai, Kunal, primary, Akdemir, Kadir C., primary, Kwong, Lawrence N., primary, Fiziev, Petko, primary, Wu, Chang-Jiun, primary, Keung, Emily Z., primary, Sharma, Sneha, primary, Samant, Neha S., primary, Williams, Maura, primary, Axelrad, Jacob B., primary, Shah, Amiksha, primary, Yang, Dong, primary, Grimm, Elizabeth A., primary, Barton, Michelle C., primary, Milton, Denai R., primary, Heffernan, Timothy P., primary, Horner, James W., primary, Ekmekcioglu, Suhendan, primary, Lazar, Alexander J., primary, Ernst, Jason, primary, and Chin, Lynda, primary

Published
2023
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