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1,094 results on '"Cherniack, Andrew D."'

1. Author Correction: Molecular profiling of 888 pediatric tumors informs future precision trials and data-sharing initiatives in pediatric cancer

Author

Forrest, Suzanne J., Gupta, Hersh, Ward, Abigail, Li, Yvonne Y., Doan, Duong, Al-Ibraheemi, Alyaa, Alexandrescu, Sanda, Bandopadhayay, Pratiti, Shusterman, Suzanne, Mullen, Elizabeth A., Collins, Natalie B., Chi, Susan N., Wright, Karen D., Kumari, Priti, Mazor, Tali, Ligon, Keith L., Shivdasani, Priyanka, Manam, Monica, MacConaill, Laura E., Ceca, Evelina, Benich, Sidney N., London, Wendy B., Schilsky, Richard L., Bruinooge, Suanna S., Guidry Auvil, Jaime M., Cerami, Ethan, Rollins, Barrett J., Meyerson, Matthew L., Lindeman, Neal I., Johnson, Bruce E., Cherniack, Andrew D., Church, Alanna J., and Janeway, Katherine A.

Published
2024
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2. Molecular profiling of 888 pediatric tumors informs future precision trials and data-sharing initiatives in pediatric cancer

Author

Forrest, Suzanne J., Gupta, Hersh, Ward, Abigail, Li, Yvonne Y., Doan, Duong, Al-Ibraheemi, Alyaa, Alexandrescu, Sanda, Bandopadhayay, Pratiti, Shusterman, Suzanne, Mullen, Elizabeth A., Collins, Natalie B., Chi, Susan N., Wright, Karen D., Kumari, Priti, Mazor, Tali, Ligon, Keith L., Shivdasani, Priyanka, Manam, Monica, MacConaill, Laura E., Ceca, Evelina, Benich, Sidney N., London, Wendy B., Schilsky, Richard L., Bruinooge, Suanna S., Guidry Auvil, Jaime M., Cerami, Ethan, Rollins, Barrett J., Meyerson, Matthew L., Lindeman, Neal I., Johnson, Bruce E., Cherniack, Andrew D., Church, Alanna J., and Janeway, Katherine A.

Published
2024
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3. Author Correction: Comprehensive mutational scanning of EGFR reveals TKI sensitivities of extracellular domain mutants

Author

Hayes, Tikvah K., Aquilanti, Elisa, Persky, Nicole S., Yang, Xiaoping, Kim, Erica E., Brenan, Lisa, Goodale, Amy B., Alan, Douglas, Sharpe, Ted, Shue, Robert E., Westlake, Lindsay, Golomb, Lior, Silverman, Brianna R., Morris, Myshal D., Fisher, Ty Running, Beyene, Eden, Li, Yvonne Y., Cherniack, Andrew D., Piccioni, Federica, Hicks, J. Kevin, Chi, Andrew S., Cahill, Daniel P., Dietrich, Jorg, Batchelor, Tracy T., Root, David E., Johannessen, Cory M., and Meyerson, Matthew

Published
2024
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4. Comprehensive mutational scanning of EGFR reveals TKI sensitivities of extracellular domain mutants

Author

Hayes, Tikvah K., Aquilanti, Elisa, Persky, Nicole S., Yang, Xiaoping, Kim, Erica E., Brenan, Lisa, Goodale, Amy B., Alan, Douglas, Sharpe, Ted, Shue, Robert E., Westlake, Lindsay, Golomb, Lior, Silverman, Brianna R., Morris, Myshal D., Fisher, Ty Running, Beyene, Eden, Li, Yvonne Y., Cherniack, Andrew D., Piccioni, Federica, Hicks, J. Kevin, Chi, Andrew S., Cahill, Daniel P., Dietrich, Jorg, Batchelor, Tracy T., Root, David E., Johannessen, Cory M., and Meyerson, Matthew

Published
2024
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5. Analysis of germline-driven ancestry-associated gene expression in cancers

Author

Chambwe, Nyasha, Sayaman, Rosalyn W, Hu, Donglei, Huntsman, Scott, Network, The Cancer Genome Analysis, Carrot-Zhang, Jian, Berger, Ashton C, Han, Seunghun, Meyerson, Matthew, Damrauer, Jeffrey S, Hoadley, Katherine A, Felau, Ina, Demchok, John A, Mensah, Michael KA, Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Knijnenburg, Theo A, Robertson, A Gordon, Yau, Christina, Benz, Christopher, Huang, Kuan-lin, Newberg, Justin Y, Frampton, Garrett M, Mashl, R Jay, Ding, Li, Romanel, Alessandro, Demichelis, Francesca, Zhou, Wanding, Laird, Peter W, Shen, Hui, Wong, Christopher K, Stuart, Joshua M, Lazar, Alexander J, Le, Xiuning, Oak, Ninad, Kemal, Anab, Caesar-Johnson, Samantha, Zenklusen, Jean C, Ziv, Elad, Beroukhim, Rameen, and Cherniack, Andrew D

Subjects
Biological Sciences, Health Sciences, Genetics, Human Genome, Biotechnology, Cancer, Good Health and Well Being, Gene Expression, Germ Cells, Humans, Neoplasms, Quantitative Trait Loci, RNA, Messenger, Cancer Genome Analysis Network, Bioinformatics, Computer sciences, Genomics, RNAseq, Sequence analysis
Abstract

Differential mRNA expression between ancestry groups can be explained by both genetic and environmental factors. We outline a computational workflow to determine the extent to which germline genetic variation explains cancer-specific molecular differences across ancestry groups. Using multi-omics datasets from The Cancer Genome Atlas (TCGA), we enumerate ancestry-informative markers colocalized with cancer-type-specific expression quantitative trait loci (e-QTLs) at ancestry-associated genes. This approach is generalizable to other settings with paired germline genotyping and mRNA expression data for a multi-ethnic cohort. For complete details on the use and execution of this protocol, please refer to Carrot-Zhang et al. (2020), Robertson et al. (2021), and Sayaman et al. (2021).

Published
2022

6. Author Correction: Comprehensive genomic characterization of HER2-low and HER2-0 breast cancer

Author

Tarantino, Paolo, Gupta, Hersh, Hughes, Melissa E., Files, Janet, Strauss, Sarah, Kirkner, Gregory, Feeney, Anne-Marie, Li, Yvonne, Garrido-Castro, Ana C., Barroso-Sousa, Romualdo, Bychkovsky, Brittany L., DiLascio, Simona, Sholl, Lynette, MacConaill, Laura, Lindeman, Neal, Johnson, Bruce E., Meyerson, Matthew, Jeselsohn, Rinath, Qiu, Xintao, Li, Rong, Long, Henry, Winer, Eric P., Dillon, Deborah, Curigliano, Giuseppe, Cherniack, Andrew D., Tolaney, Sara M., and Lin, Nancy U.

Published
2023
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7. Comprehensive genomic characterization of HER2-low and HER2-0 breast cancer

Author

Tarantino, Paolo, Gupta, Hersh, Hughes, Melissa E., Files, Janet, Strauss, Sarah, Kirkner, Gregory, Feeney, Anne-Marie, Li, Yvonne, Garrido-Castro, Ana C., Barroso-Sousa, Romualdo, Bychkovsky, Brittany L., DiLascio, Simona, Sholl, Lynette, MacConaill, Laura, Lindeman, Neal, Johnson, Bruce E., Meyerson, Matthew, Jeselsohn, Rinath, Qiu, Xintao, Li, Rong, Long, Henry, Winer, Eric P., Dillon, Deborah, Curigliano, Giuseppe, Cherniack, Andrew D., Tolaney, Sara M., and Lin, Nancy U.

Published
2023
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11. Impact of Aneuploidy and Chromosome 9p Loss on Tumor Immune Microenvironment and Immune Checkpoint Inhibitor Efficacy in NSCLC

Author

Alessi, Joao V., Wang, Xinan, Elkrief, Arielle, Ricciuti, Biagio, Li, Yvonne Y., Gupta, Hersh, Spurr, Liam F., Rizvi, Hira, Luo, Jia, Pecci, Federica, Lamberti, Giuseppe, Recondo, Gonzalo, Venkatraman, Deepti, Di Federico, Alessandro, Gandhi, Malini M., Vaz, Victor R., Nishino, Mizuki, Sholl, Lynette M., Cherniack, Andrew D., Ladanyi, Marc, Price, Adam, Richards, Allison L., Donoghue, Mark, Lindsay, James, Sharma, Bijaya, Turner, Madison M., Pfaff, Kathleen L., Felt, Kristen D., Rodig, Scott J., Lin, Xihong, Meyerson, Matthew L., Johnson, Bruce E., Christiani, David C., Schoenfeld, Adam J., and Awad, Mark M.

Published
2023
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12. Whole-genome characterization of lung adenocarcinomas lacking the RTK/RAS/RAF pathway.

Author

Carrot-Zhang, Jian, Yao, Xiaotong, Devarakonda, Siddhartha, Deshpande, Aditya, Damrauer, Jeffrey S, Silva, Tiago Chedraoui, Wong, Christopher K, Choi, Hyo Young, Felau, Ina, Robertson, A Gordon, Castro, Mauro AA, Bao, Lisui, Rheinbay, Esther, Liu, Eric Minwei, Trieu, Tuan, Haan, David, Yau, Christina, Hinoue, Toshinori, Liu, Yuexin, Shapira, Ofer, Kumar, Kiran, Mungall, Karen L, Zhang, Hailei, Lee, Jake June-Koo, Berger, Ashton, Gao, Galen F, Zhitomirsky, Binyamin, Liang, Wen-Wei, Zhou, Meng, Moorthi, Sitapriya, Berger, Alice H, Collisson, Eric A, Zody, Michael C, Ding, Li, Cherniack, Andrew D, Getz, Gad, Elemento, Olivier, Benz, Christopher C, Stuart, Josh, Zenklusen, JC, Beroukhim, Rameen, Chang, Jason C, Campbell, Joshua D, Hayes, D Neil, Yang, Lixing, Laird, Peter W, Weinstein, John N, Kwiatkowski, David J, Tsao, Ming S, Travis, William D, Khurana, Ekta, Berman, Benjamin P, Hoadley, Katherine A, Robine, Nicolas, TCGA Research Network, Meyerson, Matthew, Govindan, Ramaswamy, and Imielinski, Marcin

Subjects
TCGA Research Network, TCGA, driver, genome analysis, lung adenocarcinoma, noncoding, oncogene, precision oncology, structural variation, tumor suppressor, whole genome sequencing, Biochemistry and Cell Biology, Medical Physiology
Abstract

RTK/RAS/RAF pathway alterations (RPAs) are a hallmark of lung adenocarcinoma (LUAD). In this study, we use whole-genome sequencing (WGS) of 85 cases found to be RPA(-) by previous studies from The Cancer Genome Atlas (TCGA) to characterize the minority of LUADs lacking apparent alterations in this pathway. We show that WGS analysis uncovers RPA(+) in 28 (33%) of the 85 samples. Among the remaining 57 cases, we observe focal deletions targeting the promoter or transcription start site of STK11 (n = 7) or KEAP1 (n = 3), and promoter mutations associated with the increased expression of ILF2 (n = 6). We also identify complex structural variations associated with high-level copy number amplifications. Moreover, an enrichment of focal deletions is found in TP53 mutant cases. Our results indicate that RPA(-) cases demonstrate tumor suppressor deletions and genome instability, but lack unique or recurrent genetic lesions compensating for the lack of RPAs. Larger WGS studies of RPA(-) cases are required to understand this important LUAD subset.

Published
2021

13. Comprehensive Analysis of Genetic Ancestry and Its Molecular Correlates in Cancer

Author

Carrot-Zhang, Jian, Chambwe, Nyasha, Damrauer, Jeffrey S, Knijnenburg, Theo A, Robertson, A Gordon, Yau, Christina, Zhou, Wanding, Berger, Ashton C, Huang, Kuan-lin, Newberg, Justin Y, Mashl, R Jay, Romanel, Alessandro, Sayaman, Rosalyn W, Demichelis, Francesca, Felau, Ina, Frampton, Garrett M, Han, Seunghun, Hoadley, Katherine A, Kemal, Anab, Laird, Peter W, Lazar, Alexander J, Le, Xiuning, Oak, Ninad, Shen, Hui, Wong, Christopher K, Zenklusen, Jean C, Ziv, Elad, Network, Cancer Genome Atlas Analysis, Aguet, Francois, Ding, Li, Demchok, John A, Mensah, Michael KA, Caesar-Johnson, Samantha, Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Alfoldi, Jessica, Karczewski, Konrad J, MacArthur, Daniel G, Meyerson, Matthew, Benz, Christopher, Stuart, Joshua M, Cherniack, Andrew D, and Beroukhim, Rameen

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Genetics, Human Genome, Clinical Research, Cancer, Biotechnology, DNA Methylation, DNA-Binding Proteins, Ethnicity, F-Box-WD Repeat-Containing Protein 7, Gene Expression Regulation, Neoplastic, Genetic Predisposition to Disease, Genetics, Population, Genome, Human, Genomics, High-Throughput Nucleotide Sequencing, Humans, MicroRNAs, Mutation, Neoplasm Proteins, Neoplasms, Transcription Factors, Von Hippel-Lindau Tumor Suppressor Protein, Cancer Genome Atlas Analysis Network, TCGA, admixture, ancestry, cancer, eQTL, genomics, mRNA, methylation, miRNA, mutation, Neurosciences, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

We evaluated ancestry effects on mutation rates, DNA methylation, and mRNA and miRNA expression among 10,678 patients across 33 cancer types from The Cancer Genome Atlas. We demonstrated that cancer subtypes and ancestry-related technical artifacts are important confounders that have been insufficiently accounted for. Once accounted for, ancestry-associated differences spanned all molecular features and hundreds of genes. Biologically significant differences were usually tissue specific but not specific to cancer. However, admixture and pathway analyses suggested some of these differences are causally related to cancer. Specific findings included increased FBXW7 mutations in patients of African origin, decreased VHL and PBRM1 mutations in renal cancer patients of African origin, and decreased immune activity in bladder cancer patients of East Asian origin.

Published
2020

14. Molecular profiling identifies targeted therapy opportunities in pediatric solid cancer

Author

Church, Alanna J., Corson, Laura B., Kao, Pei-Chi, Imamovic-Tuco, Alma, Reidy, Deirdre, Doan, Duong, Kang, Wenjun, Pinto, Navin, Maese, Luke, Laetsch, Theodore W., Kim, AeRang, Colace, Susan I., Macy, Margaret E., Applebaum, Mark A., Bagatell, Rochelle, Sabnis, Amit J., Weiser, Daniel A., Glade-Bender, Julia L., Homans, Alan C., Hipps, John, Harris, Haley, Manning, Danielle, Al-Ibraheemi, Alyaa, Li, Yvonne, Gupta, Hersh, Cherniack, Andrew D., Lo, Ying-Chun, Strand, Gianna R., Lee, Lobin A., Pinches, R. Seth, Lazo De La Vega, Lorena, Harden, Maegan V., Lennon, Niall J., Choi, Seong, Comeau, Hannah, Harris, Marian H., Forrest, Suzanne J., Clinton, Catherine M., Crompton, Brian D., Kamihara, Junne, MacConaill, Laura E., Volchenboum, Samuel L., Lindeman, Neal I., Van Allen, Eliezer, DuBois, Steven G., London, Wendy B., and Janeway, Katherine A.

Published
2022
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15. The Immune Landscape of Cancer

Author

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

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

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

Published
2019

16. Next-generation characterization of the Cancer Cell Line Encyclopedia

Author

Ghandi, Mahmoud, Huang, Franklin W, Jané-Valbuena, Judit, Kryukov, Gregory V, Lo, Christopher C, McDonald, E Robert, Barretina, Jordi, Gelfand, Ellen T, Bielski, Craig M, Li, Haoxin, Hu, Kevin, Andreev-Drakhlin, Alexander Y, Kim, Jaegil, Hess, Julian M, Haas, Brian J, Aguet, François, Weir, Barbara A, Rothberg, Michael V, Paolella, Brenton R, Lawrence, Michael S, Akbani, Rehan, Lu, Yiling, Tiv, Hong L, Gokhale, Prafulla C, de Weck, Antoine, Mansour, Ali Amin, Oh, Coyin, Shih, Juliann, Hadi, Kevin, Rosen, Yanay, Bistline, Jonathan, Venkatesan, Kavitha, Reddy, Anupama, Sonkin, Dmitriy, Liu, Manway, Lehar, Joseph, Korn, Joshua M, Porter, Dale A, Jones, Michael D, Golji, Javad, Caponigro, Giordano, Taylor, Jordan E, Dunning, Caitlin M, Creech, Amanda L, Warren, Allison C, McFarland, James M, Zamanighomi, Mahdi, Kauffmann, Audrey, Stransky, Nicolas, Imielinski, Marcin, Maruvka, Yosef E, Cherniack, Andrew D, Tsherniak, Aviad, Vazquez, Francisca, Jaffe, Jacob D, Lane, Andrew A, Weinstock, David M, Johannessen, Cory M, Morrissey, Michael P, Stegmeier, Frank, Schlegel, Robert, Hahn, William C, Getz, Gad, Mills, Gordon B, Boehm, Jesse S, Golub, Todd R, Garraway, Levi A, and Sellers, William R

Subjects
Genetics, Human Genome, Lung, Cancer, Biotechnology, Lung Cancer, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Antineoplastic Agents, Biomarkers, Tumor, Cell Line, Tumor, DNA Methylation, Drug Resistance, Neoplasm, Ethnicity, Gene Editing, Histones, Humans, MicroRNAs, Molecular Targeted Therapy, Neoplasms, Protein Array Analysis, RNA Splicing, General Science & Technology
Abstract

Large panels of comprehensively characterized human cancer models, including the Cancer Cell Line Encyclopedia (CCLE), have provided a rigorous framework with which to study genetic variants, candidate targets, and small-molecule and biological therapeutics and to identify new marker-driven cancer dependencies. To improve our understanding of the molecular features that contribute to cancer phenotypes, including drug responses, here we have expanded the characterizations of cancer cell lines to include genetic, RNA splicing, DNA methylation, histone H3 modification, microRNA expression and reverse-phase protein array data for 1,072 cell lines from individuals of various lineages and ethnicities. Integration of these data with functional characterizations such as drug-sensitivity, short hairpin RNA knockdown and CRISPR-Cas9 knockout data reveals potential targets for cancer drugs and associated biomarkers. Together, this dataset and an accompanying public data portal provide a resource for the acceleration of cancer research using model cancer cell lines.

Published
2019

17. Integrative Molecular Characterization of Malignant Pleural Mesothelioma

Author

Hmeljak, Julija, Sanchez-Vega, Francisco, Hoadley, Katherine A, Shih, Juliann, Stewart, Chip, Heiman, David, Tarpey, Patrick, Danilova, Ludmila, Drill, Esther, Gibb, Ewan A, Bowlby, Reanne, Kanchi, Rupa, Osmanbeyoglu, Hatice U, Sekido, Yoshitaka, Takeshita, Jumpei, Newton, Yulia, Graim, Kiley, Gupta, Manaswi, Gay, Carl M, Diao, Lixia, Gibbs, David L, Thorsson, Vesteinn, Iype, Lisa, Kantheti, Havish, Severson, David T, Ravegnini, Gloria, Desmeules, Patrice, Jungbluth, Achim A, Travis, William D, Dacic, Sanja, Chirieac, Lucian R, Galateau-Sallé, Françoise, Fujimoto, Junya, Husain, Aliya N, Silveira, Henrique C, Rusch, Valerie W, Rintoul, Robert C, Pass, Harvey, Kindler, Hedy, Zauderer, Marjorie G, Kwiatkowski, David J, Bueno, Raphael, Tsao, Anne S, Creaney, Jenette, Lichtenberg, Tara, Leraas, Kristen, Bowen, Jay, Felau, Ina, Zenklusen, Jean Claude, Akbani, Rehan, Cherniack, Andrew D, Byers, Lauren A, Noble, Michael S, Fletcher, Jonathan A, Robertson, A Gordon, Shen, Ronglai, Aburatani, Hiroyuki, Robinson, Bruce W, Campbell, Peter, Ladanyi, Marc, Ally, Adrian, Anur, Pavana, Armenia, Joshua, Auman, J Todd, Balasundaram, Miruna, Balu, Saianand, Baylin, Stephen B, Becich, Michael, Behrens, Carmen, Beroukhim, Rameen, Bielski, Craig, Bodenheimer, Tom, Bootwalla, Moiz S, Brooks, Denise, Byers, Lauren Averett, Cárcano, Flávio M, Carlsen, Rebecca, Carvalho, Andre L, Cheung, Dorothy, Chirieac, Lucian, Cho, Juok, Chuah, Eric, Chudamani, Sudha, Cibulskis, Carrie, Cope, Leslie, Crain, Daniel, Curley, Erin, Rienzo, Assunta De, DeFreitas, Timothy, Demchok, John A, and Dhalla, Noreen

Subjects
Rare Diseases, Lung Cancer, Biotechnology, Lung, Cancer, Human Genome, Genetics, 2.1 Biological and endogenous factors, Aetiology, Good Health and Well Being, Aged, Biomarkers, Tumor, Female, Histone-Lysine N-Methyltransferase, Humans, Kaplan-Meier Estimate, Lung Neoplasms, Male, Mesothelioma, Middle Aged, Mutation, Pleural Neoplasms, Prognosis, Protein Methyltransferases, Tumor Suppressor Proteins, Ubiquitin Thiolesterase, TCGA Research Network, Oncology and Carcinogenesis
Abstract

Malignant pleural mesothelioma (MPM) is a highly lethal cancer of the lining of the chest cavity. To expand our understanding of MPM, we conducted a comprehensive integrated genomic study, including the most detailed analysis of BAP1 alterations to date. We identified histology-independent molecular prognostic subsets, and defined a novel genomic subtype with TP53 and SETDB1 mutations and extensive loss of heterozygosity. We also report strong expression of the immune-checkpoint gene VISTA in epithelioid MPM, strikingly higher than in other solid cancers, with implications for the immune response to MPM and for its immunotherapy. Our findings highlight new avenues for further investigation of MPM biology and novel therapeutic options. SIGNIFICANCE: Through a comprehensive integrated genomic study of 74 MPMs, we provide a deeper understanding of histology-independent determinants of aggressive behavior, define a novel genomic subtype with TP53 and SETDB1 mutations and extensive loss of heterozygosity, and discovered strong expression of the immune-checkpoint gene VISTA in epithelioid MPM.See related commentary by Aggarwal and Albelda, p. 1508.This article is highlighted in the In This Issue feature, p. 1494.

Published
2018

19. Diminished Efficacy of Programmed Death-(Ligand)1 Inhibition in STK11- and KEAP1-Mutant Lung Adenocarcinoma Is Affected by KRAS Mutation Status

Author

Ricciuti, Biagio, Arbour, Kathryn C., Lin, Jessica J., Vajdi, Amir, Vokes, Natalie, Hong, Lingzhi, Zhang, Jianjun, Tolstorukov, Michael Y., Li, Yvonne Y., Spurr, Liam F., Cherniack, Andrew D., Recondo, Gonzalo, Lamberti, Giuseppe, Wang, Xinan, Venkatraman, Deepti, Alessi, Joao V., Vaz, Victor R., Rizvi, Hira, Egger, Jacklynn, Plodkowski, Andrew J., Khosrowjerdi, Sara, Digumarthy, Subba, Park, Hyesun, Vaz, Nuno, Nishino, Mizuki, Sholl, Lynette M., Barbie, David, Altan, Mehmet, Heymach, John V., Skoulidis, Ferdinandos, Gainor, Justin F., Hellmann, Matthew D., and Awad, Mark M.

Published
2022
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20. A Pan-Cancer Analysis Reveals High-Frequency Genetic Alterations in Mediators of Signaling by the TGF-β Superfamily

Author

Korkut, Anil, Zaidi, Sobia, Kanchi, Rupa S, Rao, Shuyun, Gough, Nancy R, Schultz, Andre, Li, Xubin, Lorenzi, Philip L, Berger, Ashton C, Robertson, Gordon, Kwong, Lawrence N, Datto, Mike, Roszik, Jason, Ling, Shiyun, Ravikumar, Visweswaran, Manyam, Ganiraju, Rao, Arvind, Shelley, Simon, Liu, Yuexin, Ju, Zhenlin, Hansel, Donna, de Velasco, Guillermo, Pennathur, Arjun, Andersen, Jesper B, O'Rourke, Colm J, Ohshiro, Kazufumi, Jogunoori, Wilma, Nguyen, Bao-Ngoc, Li, Shulin, Osmanbeyoglu, Hatice U, Ajani, Jaffer A, Mani, Sendurai A, Houseman, Andres, Wiznerowicz, Maciej, Chen, Jian, Gu, Shoujun, Ma, Wencai, Zhang, Jiexin, Tong, Pan, Cherniack, Andrew D, Deng, Chuxia, Resar, Linda, Network, The Cancer Genome Atlas Research, Caesar-Johnson, Samantha J, Demchok, John A, Felau, Ina, Kasapi, Melpomeni, Ferguson, Martin L, Hutter, Carolyn M, Sofia, Heidi J, Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Zenklusen, Jean C, Zhang, Jiashan, Chudamani, Sudha, Liu, Jia, Lolla, Laxmi, Naresh, Rashi, Pihl, Todd, Sun, Qiang, Wan, Yunhu, Wu, Ye, Cho, Juok, DeFreitas, Timothy, Frazer, Scott, Gehlenborg, Nils, Getz, Gad, Heiman, David I, Kim, Jaegil, Lawrence, Michael S, Lin, Pei, Meier, Sam, Noble, Michael S, Saksena, Gordon, Voet, Doug, Zhang, Hailei, Bernard, Brady, Chambwe, Nyasha, Dhankani, Varsha, Knijnenburg, Theo, Kramer, Roger, Leinonen, Kalle, Miller, Michael, Reynolds, Sheila, Shmulevich, Ilya, Thorsson, Vesteinn, Zhang, Wei, Akbani, Rehan, Broom, Bradley M, Hegde, Apurva M, Li, Jun, Liang, Han, Liu, Wenbin, and Lu, Yiling

Subjects
Biological Sciences, Genetics, Cancer, Cancer Genomics, Human Genome, Biotechnology, 2.1 Biological and endogenous factors, Bone Morphogenetic Protein 5, DNA Methylation, Humans, MicroRNAs, Mutation Rate, Neoplasms, Receptor, Transforming Growth Factor-beta Type I, Signal Transduction, Smad Proteins, Transforming Growth Factor beta, Cancer Genome Atlas Research Network, DNA methylation, Pan-Cancer, TCGA, TGF-β, TGF-β pathway, The Cancer Genome Atlas, cancer, microRNA, mutation hotspot, transcription, Biochemistry and Cell Biology, Biochemistry and cell biology
Abstract

We present an integromic analysis of gene alterations that modulate transforming growth factor β (TGF-β)-Smad-mediated signaling in 9,125 tumor samples across 33 cancer types in The Cancer Genome Atlas (TCGA). Focusing on genes that encode mediators and regulators of TGF-β signaling, we found at least one genomic alteration (mutation, homozygous deletion, or amplification) in 39% of samples, with highest frequencies in gastrointestinal cancers. We identified mutation hotspots in genes that encode TGF-β ligands (BMP5), receptors (TGFBR2, AVCR2A, and BMPR2), and Smads (SMAD2 and SMAD4). Alterations in the TGF-β superfamily correlated positively with expression of metastasis-associated genes and with decreased survival. Correlation analyses showed the contributions of mutation, amplification, deletion, DNA methylation, and miRNA expression to transcriptional activity of TGF-β signaling in each cancer type. This study provides a broad molecular perspective relevant for future functional and therapeutic studies of the diverse cancer pathways mediated by the TGF-β superfamily.

Published
2018

21. Genome-scale analysis identifies paralog lethality as a vulnerability of chromosome 1p loss in cancer

Author

Viswanathan, Srinivas R, Nogueira, Marina F, Buss, Colin G, Krill-Burger, John M, Wawer, Mathias J, Malolepsza, Edyta, Berger, Ashton C, Choi, Peter S, Shih, Juliann, Taylor, Alison M, Tanenbaum, Benjamin, Pedamallu, Chandra Sekhar, Cherniack, Andrew D, Tamayo, Pablo, Strathdee, Craig A, Lage, Kasper, Carr, Steven A, Schenone, Monica, Bhatia, Sangeeta N, Vazquez, Francisca, Tsherniak, Aviad, Hahn, William C, and Meyerson, Matthew

Subjects
Cancer, Pediatric Research Initiative, Lung Cancer, Human Genome, Lung, Biotechnology, Genetics, Aetiology, 2.1 Biological and endogenous factors, Animals, Cell Line, Tumor, Cell Nucleus, Chromosomes, Human, Pair 1, Exons, Female, Gene Deletion, HEK293 Cells, Humans, Karyopherins, Mice, Mice, Nude, Neoplasms, Nuclear Proteins, RNA Splicing, RNA, Small Interfering, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Functional redundancy shared by paralog genes may afford protection against genetic perturbations, but it can also result in genetic vulnerabilities due to mutual interdependency1-5. Here, we surveyed genome-scale short hairpin RNA and CRISPR screening data on hundreds of cancer cell lines and identified MAGOH and MAGOHB, core members of the splicing-dependent exon junction complex, as top-ranked paralog dependencies6-8. MAGOHB is the top gene dependency in cells with hemizygous MAGOH deletion, a pervasive genetic event that frequently occurs due to chromosome 1p loss. Inhibition of MAGOHB in a MAGOH-deleted context compromises viability by globally perturbing alternative splicing and RNA surveillance. Dependency on IPO13, an importin-β receptor that mediates nuclear import of the MAGOH/B-Y14 heterodimer9, is highly correlated with dependency on both MAGOH and MAGOHB. Both MAGOHB and IPO13 represent dependencies in murine xenografts with hemizygous MAGOH deletion. Our results identify MAGOH and MAGOHB as reciprocal paralog dependencies across cancer types and suggest a rationale for targeting the MAGOHB-IPO13 axis in cancers with chromosome 1p deletion.

Published
2018

22. Integrated Molecular Characterization of Testicular Germ Cell Tumors

Author

Shen, Hui, Shih, Juliann, Hollern, Daniel P, Wang, Linghua, Bowlby, Reanne, Tickoo, Satish K, Thorsson, Vésteinn, Mungall, Andrew J, Newton, Yulia, Hegde, Apurva M, Armenia, Joshua, Sánchez-Vega, Francisco, Pluta, John, Pyle, Louise C, Mehra, Rohit, Reuter, Victor E, Godoy, Guilherme, Jones, Jeffrey, Shelley, Carl S, Feldman, Darren R, Vidal, Daniel O, Lessel, Davor, Kulis, Tomislav, Cárcano, Flavio M, Leraas, Kristen M, Lichtenberg, Tara M, Brooks, Denise, Cherniack, Andrew D, Cho, Juok, Heiman, David I, Kasaian, Katayoon, Liu, Minwei, Noble, Michael S, Xi, Liu, Zhang, Hailei, Zhou, Wanding, ZenKlusen, Jean C, Hutter, Carolyn M, Felau, Ina, Zhang, Jiashan, Schultz, Nikolaus, Getz, Gad, Meyerson, Matthew, Stuart, Joshua M, Akbani, Rehan, Wheeler, David, Laird, Peter W, Nathanson, Katherine L, Cortessis, Victoria K, Hoadley, Katherine A, Wheeler, David A, Hughes, Daniel, Covington, Kyle, Jayaseelan, Joy C, Korchina, Viktoriya, Lewis, Lora, Hu, Jianhong, Doddapaneni, HarshaVardhan, Muzny, Donna, Gibbs, Richard, Hollern, Daniel, Vincent, Benjamin G, Chai, Shengjie, Smith, Christof C, Auman, J Todd, Shi, Yan, Meng, Shaowu, Skelly, Tara, Tan, Donghui, Veluvolu, Umadevi, Mieczkowski, Piotr A, Jones, Corbin D, Wilkerson, Matthew D, Balu, Saianand, Bodenheimer, Tom, Hoyle, Alan P, Jefferys, Stuart R, Mose, Lisle E, Simons, Janae V, Soloway, Matthew G, Roach, Jeffrey, Parker, Joel S, Hayes, D Neil, Perou, Charles M, Saksena, Gordon, Cibulskis, Carrie, Schumacher, Steven E, Beroukhim, Rameen, Gabriel, Stacey B, and Ally, Adrian

Subjects
Urologic Diseases, Rare Diseases, Human Genome, Cancer, Biotechnology, Genetics, DNA Copy Number Variations, DNA Methylation, Gene Expression Regulation, Neoplastic, Humans, Male, MicroRNAs, Neoplasms, Germ Cell and Embryonal, Proto-Oncogene Proteins c-kit, Seminoma, Testicular Neoplasms, ras Proteins, Cancer Genome Atlas Research Network, DNA methylation, KIT, The Cancer Genome Atlas, copy number, exome sequencing, miR-375, nonseminoma, seminoma, testicular germ cell tumors, Biochemistry and Cell Biology, Medical Physiology
Abstract

We studied 137 primary testicular germ cell tumors (TGCTs) using high-dimensional assays of genomic, epigenomic, transcriptomic, and proteomic features. These tumors exhibited high aneuploidy and a paucity of somatic mutations. Somatic mutation of only three genes achieved significance-KIT, KRAS, and NRAS-exclusively in samples with seminoma components. Integrated analyses identified distinct molecular patterns that characterized the major recognized histologic subtypes of TGCT: seminoma, embryonal carcinoma, yolk sac tumor, and teratoma. Striking differences in global DNA methylation and microRNA expression between histology subtypes highlight a likely role of epigenomic processes in determining histologic fates in TGCTs. We also identified a subset of pure seminomas defined by KIT mutations, increased immune infiltration, globally demethylated DNA, and decreased KRAS copy number. We report potential biomarkers for risk stratification, such as miRNA specifically expressed in teratoma, and others with molecular diagnostic potential, such as CpH (CpA/CpC/CpT) methylation identifying embryonal carcinomas.

Published
2018

23. Comparative Molecular Analysis of Gastrointestinal Adenocarcinomas

Author

Liu, Yang, Sethi, Nilay S, Hinoue, Toshinori, Schneider, Barbara G, Cherniack, Andrew D, Sanchez-Vega, Francisco, Seoane, Jose A, Farshidfar, Farshad, Bowlby, Reanne, Islam, Mirazul, Kim, Jaegil, Chatila, Walid, Akbani, Rehan, Kanchi, Rupa S, Rabkin, Charles S, Willis, Joseph E, Wang, Kenneth K, McCall, Shannon J, Mishra, Lopa, Ojesina, Akinyemi I, Bullman, Susan, Pedamallu, Chandra Sekhar, Lazar, Alexander J, Sakai, Ryo, Network, The Cancer Genome Atlas Research, Caesar-Johnson, Samantha J, Demchok, John A, Felau, Ina, Kasapi, Melpomeni, Ferguson, Martin L, Hutter, Carolyn M, Sofia, Heidi J, Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Zenklusen, Jean C, Zhang, Jiashan, Chudamani, Sudha, Liu, Jia, Lolla, Laxmi, Naresh, Rashi, Pihl, Todd, Sun, Qiang, Wan, Yunhu, Wu, Ye, Cho, Juok, DeFreitas, Timothy, Frazer, Scott, Gehlenborg, Nils, Getz, Gad, Heiman, David I, Lawrence, Michael S, Lin, Pei, Meier, Sam, Noble, Michael S, Saksena, Gordon, Voet, Doug, Zhang, Hailei, Bernard, Brady, Chambwe, Nyasha, Dhankani, Varsha, Knijnenburg, Theo, Kramer, Roger, Leinonen, Kalle, Liu, Yuexin, Miller, Michael, Reynolds, Sheila, Shmulevich, Ilya, Thorsson, Vesteinn, Zhang, Wei, Broom, Bradley M, Hegde, Apurva M, Ju, Zhenlin, Korkut, Anil, Li, Jun, Liang, Han, Ling, Shiyun, Liu, Wenbin, Lu, Yiling, Mills, Gordon B, Ng, Kwok-Shing, Rao, Arvind, Ryan, Michael, Wang, Jing, Weinstein, John N, Zhang, Jiexin, Abeshouse, Adam, Armenia, Joshua, Chakravarty, Debyani, Chatila, Walid K, Bruijn, Inode, Gao, Jianjiong, Gross, Benjamin E, Heins, Zachary J, Kundra, Ritika, La, Konnor, and Ladanyi, Marc

Subjects
Biological Sciences, Genetics, Rare Diseases, Cancer, Human Genome, Colo-Rectal Cancer, Genetic Testing, Cancer Genomics, Biotechnology, Digestive Diseases, Adenocarcinoma, Aneuploidy, Chromosomal Instability, DNA Methylation, DNA Polymerase II, DNA-Binding Proteins, Epigenesis, Genetic, Female, Gastrointestinal Neoplasms, Gene Regulatory Networks, Heterogeneous-Nuclear Ribonucleoproteins, Humans, Male, Microsatellite Instability, MutL Protein Homolog 1, Mutation, Poly-ADP-Ribose Binding Proteins, Polymorphism, Single Nucleotide, Proto-Oncogene Proteins p21(ras), RNA-Binding Proteins, SOX9 Transcription Factor, Cancer Genome Atlas Research Network, cancer, colon, colorectal, epigenetic, esophagus, genomic, methylation, rectum, stomach, tumor, Neurosciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

We analyzed 921 adenocarcinomas of the esophagus, stomach, colon, and rectum to examine shared and distinguishing molecular characteristics of gastrointestinal tract adenocarcinomas (GIACs). Hypermutated tumors were distinct regardless of cancer type and comprised those enriched for insertions/deletions, representing microsatellite instability cases with epigenetic silencing of MLH1 in the context of CpG island methylator phenotype, plus tumors with elevated single-nucleotide variants associated with mutations in POLE. Tumors with chromosomal instability were diverse, with gastroesophageal adenocarcinomas harboring fragmented genomes associated with genomic doubling and distinct mutational signatures. We identified a group of tumors in the colon and rectum lacking hypermutation and aneuploidy termed genome stable and enriched in DNA hypermethylation and mutations in KRAS, SOX9, and PCBP1.

Published
2018

24. Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

Author

Campbell, Joshua D, Yau, Christina, Bowlby, Reanne, Liu, Yuexin, Brennan, Kevin, Fan, Huihui, Taylor, Alison M, Wang, Chen, Walter, Vonn, Akbani, Rehan, Byers, Lauren Averett, Creighton, Chad J, Coarfa, Cristian, Shih, Juliann, Cherniack, Andrew D, Gevaert, Olivier, Prunello, Marcos, Shen, Hui, Anur, Pavana, Chen, Jianhong, Cheng, Hui, Hayes, D Neil, Bullman, Susan, Pedamallu, Chandra Sekhar, Ojesina, Akinyemi I, Sadeghi, Sara, Mungall, Karen L, Robertson, A Gordon, Benz, Christopher, Schultz, Andre, Kanchi, Rupa S, Gay, Carl M, Hegde, Apurva, Diao, Lixia, Wang, Jing, Ma, Wencai, Sumazin, Pavel, Chiu, Hua-Sheng, Chen, Ting-Wen, Gunaratne, Preethi, Donehower, Larry, Rader, Janet S, Zuna, Rosemary, Al-Ahmadie, Hikmat, Lazar, Alexander J, Flores, Elsa R, Tsai, Kenneth Y, Zhou, Jane H, Rustgi, Anil K, Drill, Esther, Shen, Ronglei, Wong, Christopher K, Network, The Cancer Genome Atlas Research, Caesar-Johnson, Samantha J, Demchok, John A, Felau, Ina, Kasapi, Melpomeni, Ferguson, Martin L, Hutter, Carolyn M, Sofia, Heidi J, Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Zenklusen, Jean C, Zhang, Jiashan, Chudamani, Sudha, Liu, Jia, Lolla, Laxmi, Naresh, Rashi, Pihl, Todd, Sun, Qiang, Wan, Yunhu, Wu, Ye, Cho, Juok, DeFreitas, Timothy, Frazer, Scott, Gehlenborg, Nils, Getz, Gad, Heiman, David I, Kim, Jaegil, Lawrence, Michael S, Lin, Pei, Meier, Sam, Noble, Michael S, Saksena, Gordon, Voet, Doug, Zhang, Hailei, Bernard, Brady, Chambwe, Nyasha, Dhankani, Varsha, Knijnenburg, Theo, Kramer, Roger, Leinonen, Kalle, Miller, Michael, Reynolds, Sheila, Shmulevich, Ilya, Thorsson, Vesteinn, and Zhang, Wei

Subjects
Biological Sciences, Genetics, Human Genome, Sexually Transmitted Infections, Cancer Genomics, Biotechnology, Cancer, Infectious Diseases, 2.1 Biological and endogenous factors, Carcinoma, Squamous Cell, Cell Line, Tumor, DNA Methylation, Epithelial-Mesenchymal Transition, Gene Expression Regulation, Neoplastic, Genomics, Humans, Metabolic Networks and Pathways, Polymorphism, Genetic, Cancer Genome Atlas Research Network, bladder carcinoma with squamous differentiation, cervical squamous cell carcinoma, esophageal squamous cell carcinoma, genomics, head and neck squamous cell carcinoma, human papillomavirus, lung squamous cell carcinoma, proteomics, transcriptomics, Biochemistry and Cell Biology, Medical Physiology, Biological sciences
Abstract

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smoking and/or human papillomavirus (HPV). SCCs harbor 3q, 5p, and other recurrent chromosomal copy-number alterations (CNAs), DNA mutations, and/or aberrant methylation of genes and microRNAs, which are correlated with the expression of multi-gene programs linked to squamous cell stemness, epithelial-to-mesenchymal differentiation, growth, genomic integrity, oxidative damage, death, and inflammation. Low-CNA SCCs tended to be HPV(+) and display hypermethylation with repression of TET1 demethylase and FANCF, previously linked to predisposition to SCC, or harbor mutations affecting CASP8, RAS-MAPK pathways, chromatin modifiers, and immunoregulatory molecules. We uncovered hypomethylation of the alternative promoter that drives expression of the ΔNp63 oncogene and embedded miR944. Co-expression of immune checkpoint, T-regulatory, and Myeloid suppressor cells signatures may explain reduced efficacy of immune therapy. These findings support possibilities for molecular classification and therapeutic approaches.

Published
2018

25. The Immune Landscape of Cancer

Author

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

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

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

Published
2018

26. Perspective on Oncogenic Processes at the End of the Beginning of Cancer Genomics

Author

Ding, Li, Bailey, Matthew H, Porta-Pardo, Eduard, Thorsson, Vesteinn, Colaprico, Antonio, Bertrand, Denis, Gibbs, David L, Weerasinghe, Amila, Huang, Kuan-lin, Tokheim, Collin, Cortés-Ciriano, Isidro, Jayasinghe, Reyka, Chen, Feng, Yu, Lihua, Sun, Sam, Olsen, Catharina, Kim, Jaegil, Taylor, Alison M, Cherniack, Andrew D, Akbani, Rehan, Suphavilai, Chayaporn, Nagarajan, Niranjan, Stuart, Joshua M, Mills, Gordon B, Wyczalkowski, Matthew A, Vincent, Benjamin G, Hutter, Carolyn M, Zenklusen, Jean Claude, Hoadley, Katherine A, Wendl, Michael C, Shmulevich, llya, Lazar, Alexander J, Wheeler, David A, Getz, Gad, Network, The Cancer Genome Atlas Research, Caesar-Johnson, Samantha J, Demchok, John A, Felau, Ina, Kasapi, Melpomeni, Ferguson, Martin L, Sofia, Heidi J, Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Zenklusen, Jean C, Zhang, Jiashan, Chudamani, Sudha, Liu, Jia, Lolla, Laxmi, Naresh, Rashi, Pihl, Todd, Sun, Qiang, Wan, Yunhu, Wu, Ye, Cho, Juok, DeFreitas, Timothy, Frazer, Scott, Gehlenborg, Nils, Heiman, David I, Lawrence, Michael S, Lin, Pei, Meier, Sam, Noble, Michael S, Saksena, Gordon, Voet, Doug, Zhang, Hailei, Bernard, Brady, Chambwe, Nyasha, Dhankani, Varsha, Knijnenburg, Theo, Kramer, Roger, Leinonen, Kalle, Liu, Yuexin, Miller, Michael, Reynolds, Sheila, Shmulevich, Ilya, Zhang, Wei, Broom, Bradley M, Hegde, Apurva M, Ju, Zhenlin, Kanchi, Rupa S, Korkut, Anil, Li, Jun, Liang, Han, Ling, Shiyun, Liu, Wenbin, Lu, Yiling, Ng, Kwok-Shing, Rao, Arvind, Ryan, Michael, Wang, Jing, Weinstein, John N, Zhang, Jiexin, and Abeshouse, Adam

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Bioinformatics and Computational Biology, Genetics, Oncology and Carcinogenesis, Human Genome, Biotechnology, Cancer, Cancer Genomics, 2.1 Biological and endogenous factors, Good Health and Well Being, Carcinogenesis, DNA Repair, Databases, Genetic, Genes, Neoplasm, Genomics, Humans, Metabolic Networks and Pathways, Microsatellite Instability, Mutation, Neoplasms, Transcriptome, Tumor Microenvironment, Cancer Genome Atlas Research Network, TCGA, cancer, cancer genomics, omics, oncogenic process, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

The Cancer Genome Atlas (TCGA) has catalyzed systematic characterization of diverse genomic alterations underlying human cancers. At this historic junction marking the completion of genomic characterization of over 11,000 tumors from 33 cancer types, we present our current understanding of the molecular processes governing oncogenesis. We illustrate our insights into cancer through synthesis of the findings of the TCGA PanCancer Atlas project on three facets of oncogenesis: (1) somatic driver mutations, germline pathogenic variants, and their interactions in the tumor; (2) the influence of the tumor genome and epigenome on transcriptome and proteome; and (3) the relationship between tumor and the microenvironment, including implications for drugs targeting driver events and immunotherapies. These results will anchor future characterization of rare and common tumor types, primary and relapsed tumors, and cancers across ancestry groups and will guide the deployment of clinical genomic sequencing.

Published
2018

27. A Comprehensive Pan-Cancer Molecular Study of Gynecologic and Breast Cancers

Author

Berger, Ashton C, Korkut, Anil, Kanchi, Rupa S, Hegde, Apurva M, Lenoir, Walter, Liu, Wenbin, Liu, Yuexin, Fan, Huihui, Shen, Hui, Ravikumar, Visweswaran, Rao, Arvind, Schultz, Andre, Li, Xubin, Sumazin, Pavel, Williams, Cecilia, Mestdagh, Pieter, Gunaratne, Preethi H, Yau, Christina, Bowlby, Reanne, Robertson, A Gordon, Tiezzi, Daniel G, Wang, Chen, Cherniack, Andrew D, Godwin, Andrew K, Kuderer, Nicole M, Rader, Janet S, Zuna, Rosemary E, Sood, Anil K, Lazar, Alexander J, Ojesina, Akinyemi I, Adebamowo, Clement, Adebamowo, Sally N, Baggerly, Keith A, Chen, Ting-Wen, Chiu, Hua-Sheng, Lefever, Steve, Liu, Liang, MacKenzie, Karen, Orsulic, Sandra, Roszik, Jason, Shelley, Carl Simon, Song, Qianqian, Vellano, Christopher P, Wentzensen, Nicolas, Network, The Cancer Genome Atlas Research, Caesar-Johnson, Samantha J, Demchok, John A, Felau, Ina, Kasapi, Melpomeni, Ferguson, Martin L, Hutter, Carolyn M, Sofia, Heidi J, Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Zenklusen, Jean C, Zhang, Jiashan, Chudamani, Sudha, Liu, Jia, Lolla, Laxmi, Naresh, Rashi, Pihl, Todd, Sun, Qiang, Wan, Yunhu, Wu, Ye, Cho, Juok, DeFreitas, Timothy, Frazer, Scott, Gehlenborg, Nils, Getz, Gad, Heiman, David I, Kim, Jaegil, Lawrence, Michael S, Lin, Pei, Meier, Sam, Noble, Michael S, Saksena, Gordon, Voet, Doug, Zhang, Hailei, Bernard, Brady, Chambwe, Nyasha, Dhankani, Varsha, Knijnenburg, Theo, Kramer, Roger, Leinonen, Kalle, Miller, Michael, Reynolds, Sheila, Shmulevich, Ilya, Thorsson, Vesteinn, Zhang, Wei, Akbani, Rehan, Broom, Bradley M, Ju, Zhenlin, Li, Jun, Liang, Han, and Ling, Shiyun

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Breast Cancer, Genetics, Precision Medicine, Cancer Genomics, Women's Health, Cancer, Human Genome, 4.1 Discovery and preclinical testing of markers and technologies, Breast Neoplasms, DNA Copy Number Variations, Databases, Genetic, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Gene Regulatory Networks, Genetic Predisposition to Disease, Genital Neoplasms, Female, Humans, Mutation, Organ Specificity, Prognosis, RNA, Long Noncoding, Receptors, Estrogen, Cancer Genome Atlas Research Network, TCGA, The Cancer Genome Atlas, breast cancer, cervical cancer, gynecologic cancer, omics, ovarian cancer, pan-gynecologic, uterine cancer, uterine carcinosarcoma, Neurosciences, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

We analyzed molecular data on 2,579 tumors from The Cancer Genome Atlas (TCGA) of four gynecological types plus breast. Our aims were to identify shared and unique molecular features, clinically significant subtypes, and potential therapeutic targets. We found 61 somatic copy-number alterations (SCNAs) and 46 significantly mutated genes (SMGs). Eleven SCNAs and 11 SMGs had not been identified in previous TCGA studies of the individual tumor types. We found functionally significant estrogen receptor-regulated long non-coding RNAs (lncRNAs) and gene/lncRNA interaction networks. Pathway analysis identified subtypes with high leukocyte infiltration, raising potential implications for immunotherapy. Using 16 key molecular features, we identified five prognostic subtypes and developed a decision tree that classified patients into the subtypes based on just six features that are assessable in clinical laboratories.

Published
2018

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

Author

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

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

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

Published
2018

29. Pathogenic Germline Variants in 10,389 Adult Cancers

Author

Huang, Kuan-lin, Mashl, R Jay, Wu, Yige, Ritter, Deborah I, Wang, Jiayin, Oh, Clara, Paczkowska, Marta, Reynolds, Sheila, Wyczalkowski, Matthew A, Oak, Ninad, Scott, Adam D, Krassowski, Michal, Cherniack, Andrew D, Houlahan, Kathleen E, Jayasinghe, Reyka, Wang, Liang-Bo, Zhou, Daniel Cui, Liu, Di, Cao, Song, Kim, Young Won, Koire, Amanda, McMichael, Joshua F, Hucthagowder, Vishwanathan, Kim, Tae-Beom, Hahn, Abigail, Wang, Chen, McLellan, Michael D, Al-Mulla, Fahd, Johnson, Kimberly J, Network, The Cancer Genome Atlas Research, Caesar-Johnson, Samantha J, Demchok, John A, Felau, Ina, Kasapi, Melpomeni, Ferguson, Martin L, Hutter, Carolyn M, Sofia, Heidi J, Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Zenklusen, Jean C, Zhang, Jiashan, Chudamani, Sudha, Liu, Jia, Lolla, Laxmi, Naresh, Rashi, Pihl, Todd, Sun, Qiang, Wan, Yunhu, Wu, Ye, Cho, Juok, DeFreitas, Timothy, Frazer, Scott, Gehlenborg, Nils, Getz, Gad, Heiman, David I, Kim, Jaegil, Lawrence, Michael S, Lin, Pei, Meier, Sam, Noble, Michael S, Saksena, Gordon, Voet, Doug, Zhang, Hailei, Bernard, Brady, Chambwe, Nyasha, Dhankani, Varsha, Knijnenburg, Theo, Kramer, Roger, Leinonen, Kalle, Liu, Yuexin, Miller, Michael, Shmulevich, Ilya, Thorsson, Vesteinn, Zhang, Wei, Akbani, Rehan, Broom, Bradley M, Hegde, Apurva M, Ju, Zhenlin, Kanchi, Rupa S, Korkut, Anil, Li, Jun, Liang, Han, Ling, Shiyun, Liu, Wenbin, Lu, Yiling, Mills, Gordon B, Ng, Kwok-Shing, Rao, Arvind, Ryan, Michael, Wang, Jing, Weinstein, John N, Zhang, Jiexin, Abeshouse, Adam, Armenia, Joshua, Chakravarty, Debyani, Chatila, Walid K, de Bruijn, Ino, and Gao, Jianjiong

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Oncology and Carcinogenesis, Cancer, Rare Diseases, Prevention, Cancer Genomics, Human Genome, 2.1 Biological and endogenous factors, DNA Copy Number Variations, Databases, Genetic, Gene Deletion, Gene Frequency, Genetic Predisposition to Disease, Genotype, Germ Cells, Germ-Line Mutation, Humans, Loss of Heterozygosity, Mutation, Missense, Neoplasms, Polymorphism, Single Nucleotide, Proto-Oncogene Proteins c-met, Proto-Oncogene Proteins c-ret, Tumor Suppressor Proteins, Cancer Genome Atlas Research Network, LOH, cancer predisposition, germline and somatic genomes, variant pathogenicity, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

We conducted the largest investigation of predisposition variants in cancer to date, discovering 853 pathogenic or likely pathogenic variants in 8% of 10,389 cases from 33 cancer types. Twenty-one genes showed single or cross-cancer associations, including novel associations of SDHA in melanoma and PALB2 in stomach adenocarcinoma. The 659 predisposition variants and 18 additional large deletions in tumor suppressors, including ATM, BRCA1, and NF1, showed low gene expression and frequent (43%) loss of heterozygosity or biallelic two-hit events. We also discovered 33 such variants in oncogenes, including missenses in MET, RET, and PTPN11 associated with high gene expression. We nominated 47 additional predisposition variants from prioritized VUSs supported by multiple evidences involving case-control frequency, loss of heterozygosity, expression effect, and co-localization with mutations and modified residues. Our integrative approach links rare predisposition variants to functional consequences, informing future guidelines of variant classification and germline genetic testing in cancer.

Published
2018

30. Machine Learning Detects Pan-cancer Ras Pathway Activation in The Cancer Genome Atlas

Author

Way, Gregory P, Sanchez-Vega, Francisco, La, Konnor, Armenia, Joshua, Chatila, Walid K, Luna, Augustin, Sander, Chris, Cherniack, Andrew D, Mina, Marco, Ciriello, Giovanni, Schultz, Nikolaus, Network, The Cancer Genome Atlas Research, Caesar-Johnson, Samantha J, Demchok, John A, Felau, Ina, Kasapi, Melpomeni, Ferguson, Martin L, Hutter, Carolyn M, Sofia, Heidi J, Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Zenklusen, Jean C, Zhang, Jiashan, Chudamani, Sudha, Liu, Jia, Lolla, Laxmi, Naresh, Rashi, Pihl, Todd, Sun, Qiang, Wan, Yunhu, Wu, Ye, Cho, Juok, DeFreitas, Timothy, Frazer, Scott, Gehlenborg, Nils, Getz, Gad, Heiman, David I, Kim, Jaegil, Lawrence, Michael S, Lin, Pei, Meier, Sam, Noble, Michael S, Saksena, Gordon, Voet, Doug, Zhang, Hailei, Bernard, Brady, Chambwe, Nyasha, Dhankani, Varsha, Knijnenburg, Theo, Kramer, Roger, Leinonen, Kalle, Liu, Yuexin, Miller, Michael, Reynolds, Sheila, Shmulevich, Ilya, Thorsson, Vesteinn, Zhang, Wei, Akbani, Rehan, Broom, Bradley M, Hegde, Apurva M, Ju, Zhenlin, Kanchi, Rupa S, Korkut, Anil, Li, Jun, Liang, Han, Ling, Shiyun, Liu, Wenbin, Lu, Yiling, Mills, Gordon B, Ng, Kwok-Shing, Rao, Arvind, Ryan, Michael, Wang, Jing, Weinstein, John N, Zhang, Jiexin, Abeshouse, Adam, Chakravarty, Debyani, de Bruijn, Ino, Gao, Jianjiong, Gross, Benjamin E, Heins, Zachary J, Kundra, Ritika, Ladanyi, Marc, Nissan, Moriah G, Ochoa, Angelica, Phillips, Sarah M, Reznik, Ed, Sheridan, Robert, Sumer, S Onur, Sun, Yichao, Taylor, Barry S, and Wang, Jioajiao

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Genetics, Machine Learning and Artificial Intelligence, Networking and Information Technology R&D (NITRD), Cancer Genomics, Cancer, Precision Medicine, Human Genome, Good Health and Well Being, Cell Line, Tumor, Gene Expression Regulation, Neoplastic, Genome, Human, Humans, Machine Learning, Neoplasms, Signal Transduction, ras Proteins, Cancer Genome Atlas Research Network, Gene expression, HRAS, KRAS, NF1, NRAS, Ras, TCGA, drug sensitivity, machine learning, pan-cancer, Biochemistry and Cell Biology, Medical Physiology, Biological sciences
Abstract

Precision oncology uses genomic evidence to match patients with treatment but often fails to identify all patients who may respond. The transcriptome of these "hidden responders" may reveal responsive molecular states. We describe and evaluate a machine-learning approach to classify aberrant pathway activity in tumors, which may aid in hidden responder identification. The algorithm integrates RNA-seq, copy number, and mutations from 33 different cancer types across The Cancer Genome Atlas (TCGA) PanCanAtlas project to predict aberrant molecular states in tumors. Applied to the Ras pathway, the method detects Ras activation across cancer types and identifies phenocopying variants. The model, trained on human tumors, can predict response to MEK inhibitors in wild-type Ras cell lines. We also present data that suggest that multiple hits in the Ras pathway confer increased Ras activity. The transcriptome is underused in precision oncology and, combined with machine learning, can aid in the identification of hidden responders.

Published
2018

31. An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

Author

Liu, Jianfang, Lichtenberg, Tara, Hoadley, Katherine A, Poisson, Laila M, Lazar, Alexander J, Cherniack, Andrew D, Kovatich, Albert J, Benz, Christopher C, Levine, Douglas A, Lee, Adrian V, Omberg, Larsson, Wolf, Denise M, Shriver, Craig D, Thorsson, Vesteinn, Network, The Cancer Genome Atlas Research, Caesar-Johnson, Samantha J, Demchok, John A, Felau, Ina, Kasapi, Melpomeni, Ferguson, Martin L, Hutter, Carolyn M, Sofia, Heidi J, Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Zenklusen, Jean C, Zhang, Jiashan, Chudamani, Sudha, Liu, Jia, Lolla, Laxmi, Naresh, Rashi, Pihl, Todd, Sun, Qiang, Wan, Yunhu, Wu, Ye, Cho, Juok, DeFreitas, Timothy, Frazer, Scott, Gehlenborg, Nils, Getz, Gad, Heiman, David I, Kim, Jaegil, Lawrence, Michael S, Lin, Pei, Meier, Sam, Noble, Michael S, Saksena, Gordon, Voet, Doug, Zhang, Hailei, Bernard, Brady, Chambwe, Nyasha, Dhankani, Varsha, Knijnenburg, Theo, Kramer, Roger, Leinonen, Kalle, Liu, Yuexin, Miller, Michael, Reynolds, Sheila, Shmulevich, Ilya, Zhang, Wei, Akbani, Rehan, Broom, Bradley M, Hegde, Apurva M, Ju, Zhenlin, Kanchi, Rupa S, Korkut, Anil, Li, Jun, Liang, Han, Ling, Shiyun, Liu, Wenbin, Lu, Yiling, Mills, Gordon B, Ng, Kwok-Shing, Rao, Arvind, Ryan, Michael, Wang, Jing, Weinstein, John N, Zhang, Jiexin, Abeshouse, Adam, Armenia, Joshua, Chakravarty, Debyani, Chatila, Walid K, de Bruijn, Ino, Gao, Jianjiong, Gross, Benjamin E, Heins, Zachary J, Kundra, Ritika, La, Konnor, Ladanyi, Marc, Luna, Augustin, Nissan, Moriah G, Ochoa, Angelica, Phillips, Sarah M, Reznik, Ed, Sanchez-Vega, Francisco, Sander, Chris, Schultz, Nikolaus, Sheridan, Robert, and Sumer, S Onur

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Human Genome, Genetics, Cancer Genomics, Women's Health, Networking and Information Technology R&D (NITRD), Cancer, Biotechnology, Precision Medicine, Good Health and Well Being, Databases, Genetic, Genomics, Humans, Kaplan-Meier Estimate, Neoplasms, Proportional Hazards Models, Cancer Genome Atlas Research Network, Cox proportional hazards regression model, TCGA, The Cancer Genome Atlas, clinical data resource, disease-free interval, disease-specific survival, follow-up time, overall survival, progression-free interval, translational research, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale.

Published
2018

32. Genomic and Molecular Landscape of DNA Damage Repair Deficiency across The Cancer Genome Atlas

Author

Knijnenburg, Theo A, Wang, Linghua, Zimmermann, Michael T, Chambwe, Nyasha, Gao, Galen F, Cherniack, Andrew D, Fan, Huihui, Shen, Hui, Way, Gregory P, Greene, Casey S, Liu, Yuexin, Akbani, Rehan, Feng, Bin, Donehower, Lawrence A, Miller, Chase, Shen, Yang, Karimi, Mostafa, Chen, Haoran, Kim, Pora, Jia, Peilin, Shinbrot, Eve, Zhang, Shaojun, Liu, Jianfang, Hu, Hai, Bailey, Matthew H, Yau, Christina, Wolf, Denise, Zhao, Zhongming, Weinstein, John N, Li, Lei, Ding, Li, Mills, Gordon B, Laird, Peter W, Wheeler, David A, Shmulevich, Ilya, Network, The Cancer Genome Atlas Research, Caesar-Johnson, Samantha J, Demchok, John A, Felau, Ina, Kasapi, Melpomeni, Ferguson, Martin L, Hutter, Carolyn M, Sofia, Heidi J, Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Zenklusen, Jean C, Zhang, Jiashan, Chudamani, Sudha, Liu, Jia, Lolla, Laxmi, Naresh, Rashi, Pihl, Todd, Sun, Qiang, Wan, Yunhu, Wu, Ye, Cho, Juok, DeFreitas, Timothy, Frazer, Scott, Gehlenborg, Nils, Getz, Gad, Heiman, David I, Kim, Jaegil, Lawrence, Michael S, Lin, Pei, Meier, Sam, Noble, Michael S, Saksena, Gordon, Voet, Doug, Zhang, Hailei, Bernard, Brady, Dhankani, Varsha, Knijnenburg, Theo, Kramer, Roger, Leinonen, Kalle, Miller, Michael, Reynolds, Sheila, Thorsson, Vesteinn, Zhang, Wei, Broom, Bradley M, Hegde, Apurva M, Ju, Zhenlin, Kanchi, Rupa S, Korkut, Anil, Li, Jun, Liang, Han, Ling, Shiyun, Liu, Wenbin, Lu, Yiling, Ng, Kwok-Shing, Rao, Arvind, Ryan, Michael, Wang, Jing, and Zhang, Jiexin

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Genetics, Cancer Genomics, Human Genome, Women's Health, Rare Diseases, Cancer, Ovarian Cancer, Orphan Drug, 2.1 Biological and endogenous factors, Cell Line, Tumor, DNA Damage, Gene Silencing, Genome, Human, Humans, Loss of Heterozygosity, Machine Learning, Mutation, Neoplasms, Recombinational DNA Repair, Tumor Suppressor Proteins, Cancer Genome Atlas Research Network, DNA damage footprints, DNA damage repair, The Cancer Genome Atlas PanCanAtlas project, epigenetic silencing, integrative statistical analysis, mutational signatures, protein structure analysis, somatic copy-number alterations, somatic mutations, Biochemistry and Cell Biology, Medical Physiology, Biological sciences
Abstract

DNA damage repair (DDR) pathways modulate cancer risk, progression, and therapeutic response. We systematically analyzed somatic alterations to provide a comprehensive view of DDR deficiency across 33 cancer types. Mutations with accompanying loss of heterozygosity were observed in over 1/3 of DDR genes, including TP53 and BRCA1/2. Other prevalent alterations included epigenetic silencing of the direct repair genes EXO5, MGMT, and ALKBH3 in ∼20% of samples. Homologous recombination deficiency (HRD) was present at varying frequency in many cancer types, most notably ovarian cancer. However, in contrast to ovarian cancer, HRD was associated with worse outcomes in several other cancers. Protein structure-based analyses allowed us to predict functional consequences of rare, recurrent DDR mutations. A new machine-learning-based classifier developed from gene expression data allowed us to identify alterations that phenocopy deleterious TP53 mutations. These frequent DDR gene alterations in many human cancers have functional consequences that may determine cancer progression and guide therapy.

Published
2018

33. Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Author

Schaub, Franz X, Dhankani, Varsha, Berger, Ashton C, Trivedi, Mihir, Richardson, Anne B, Shaw, Reid, Zhao, Wei, Zhang, Xiaoyang, Ventura, Andrea, Liu, Yuexin, Ayer, Donald E, Hurlin, Peter J, Cherniack, Andrew D, Eisenman, Robert N, Bernard, Brady, Grandori, Carla, Network, The Cancer Genome Atlas, Caesar-Johnson, Samantha J, Demchok, John A, Felau, Ina, Kasapi, Melpomeni, Ferguson, Martin L, Hutter, Carolyn M, Sofia, Heidi J, Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Zenklusen, Jean C, Zhang, Jiashan, Chudamani, Sudha, Liu, Jia, Lolla, Laxmi, Naresh, Rashi, Pihl, Todd, Sun, Qiang, Wan, Yunhu, Wu, Ye, Cho, Juok, DeFreitas, Timothy, Frazer, Scott, Gehlenborg, Nils, Getz, Gad, Heiman, David I, Kim, Jaegil, Lawrence, Michael S, Lin, Pei, Meier, Sam, Noble, Michael S, Saksena, Gordon, Voet, Doug, Zhang, Hailei, Chambwe, Nyasha, Knijnenburg, Theo, Kramer, Roger, Leinonen, Kalle, Miller, Michael, Reynolds, Sheila, Shmulevich, Ilya, Thorsson, Vesteinn, Zhang, Wei, Akbani, Rehan, Broom, Bradley M, Hegde, Apurva M, Ju, Zhenlin, Kanchi, Rupa S, Korkut, Anil, Li, Jun, Liang, Han, Ling, Shiyun, Liu, Wenbin, Lu, Yiling, Mills, Gordon B, Ng, Kwok-Shing, Rao, Arvind, Ryan, Michael, Wang, Jing, Weinstein, John N, Zhang, Jiexin, Abeshouse, Adam, Armenia, Joshua, Chakravarty, Debyani, Chatila, Walid K, de Bruijn, Ino, Gao, Jianjiong, Gross, Benjamin E, Heins, Zachary J, Kundra, Ritika, La, Konnor, Ladanyi, Marc, Luna, Augustin, Nissan, Moriah G, Ochoa, Angelica, Phillips, Sarah M, Reznik, Ed, Sanchez-Vega, Francisco, Sander, Chris, and Schultz, Nikolaus

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Cancer Genomics, Human Genome, Cancer, Genetics, Biotechnology, 2.1 Biological and endogenous factors, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Basic Helix-Loop-Helix Transcription Factors, Biomarkers, Tumor, Carcinogenesis, Chromatin, Computational Biology, Genes, myc, Genomics, Humans, Neoplasms, Oncogenes, Proteomics, Proto-Oncogene Proteins c-myc, Repressor Proteins, Signal Transduction, Transcription Factors, Cancer Genome Atlas Network, MAX, MNT, MYC genomic alterations, TCGA, The Cancer Genome Atlas, Biochemistry and Cell Biology, Biochemistry and cell biology
Abstract

Although the MYC oncogene has been implicated in cancer, a systematic assessment of alterations of MYC, related transcription factors, and co-regulatory proteins, forming the proximal MYC network (PMN), across human cancers is lacking. Using computational approaches, we define genomic and proteomic features associated with MYC and the PMN across the 33 cancers of The Cancer Genome Atlas. Pan-cancer, 28% of all samples had at least one of the MYC paralogs amplified. In contrast, the MYC antagonists MGA and MNT were the most frequently mutated or deleted members, proposing a role as tumor suppressors. MYC alterations were mutually exclusive with PIK3CA, PTEN, APC, or BRAF alterations, suggesting that MYC is a distinct oncogenic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such as immune response and growth factor signaling; chromatin, translation, and DNA replication/repair were conserved pan-cancer. This analysis reveals insights into MYC biology and is a reference for biomarkers and therapeutics for cancers with alterations of MYC or the PMN.

Published
2018

34. 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

35. 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

36. Supplementary Figure 1 from RAS/RAF Comutation and ERBB2 Copy Number Modulates HER2 Heterogeneity and Responsiveness to HER2-directed Therapy in Colorectal Cancer

Author

Singh, Harshabad, primary, Sahgal, Pranshu, primary, Kapner, Kevin, primary, Corsello, Steven M., primary, Gupta, Hersh, primary, Gujrathi, Rahul, primary, Li, Yvonne Y., primary, Cherniack, Andrew D., primary, El Alam, Raquelle, primary, Kerfoot, Joseph, primary, Andrews, Elizabeth, primary, Lee, Annette, primary, Nambiar, Chetan, primary, Hannigan, Alison M., primary, Remland, Joshua, primary, Brais, Lauren, primary, Leahy, Meghan E., primary, Rubinson, Douglas A., primary, Schlechter, Benjamin L., primary, Meyerson, Matthew, primary, Kuang, Yanan, primary, Paweletz, Cloud P., primary, Lee, Jessica K., primary, Quintanilha, Julia C.F., primary, Aguirre, Andrew J., primary, Perez, Kimberly J., primary, Huffman, Brandon M., primary, Rossi, Humberto, primary, Abrams, Thomas A., primary, Kabraji, Sheheryar, primary, Trusolino, Livio, primary, Bertotti, Andrea, primary, Sicinska, Ewa T., primary, Parikh, Aparna R., primary, Wolpin, Brian M., primary, Schrock, Alexa B., primary, Giannakis, Marios, primary, Ng, Kimmie, primary, Meyerhardt, Jeffrey A., primary, Hornick, Jason L., primary, Sethi, Nilay S., primary, and Cleary, James M., primary

Published
2024
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37. Supplementary Table 1 from RAS/RAF Comutation and ERBB2 Copy Number Modulates HER2 Heterogeneity and Responsiveness to HER2-directed Therapy in Colorectal Cancer

Author

Singh, Harshabad, primary, Sahgal, Pranshu, primary, Kapner, Kevin, primary, Corsello, Steven M., primary, Gupta, Hersh, primary, Gujrathi, Rahul, primary, Li, Yvonne Y., primary, Cherniack, Andrew D., primary, El Alam, Raquelle, primary, Kerfoot, Joseph, primary, Andrews, Elizabeth, primary, Lee, Annette, primary, Nambiar, Chetan, primary, Hannigan, Alison M., primary, Remland, Joshua, primary, Brais, Lauren, primary, Leahy, Meghan E., primary, Rubinson, Douglas A., primary, Schlechter, Benjamin L., primary, Meyerson, Matthew, primary, Kuang, Yanan, primary, Paweletz, Cloud P., primary, Lee, Jessica K., primary, Quintanilha, Julia C.F., primary, Aguirre, Andrew J., primary, Perez, Kimberly J., primary, Huffman, Brandon M., primary, Rossi, Humberto, primary, Abrams, Thomas A., primary, Kabraji, Sheheryar, primary, Trusolino, Livio, primary, Bertotti, Andrea, primary, Sicinska, Ewa T., primary, Parikh, Aparna R., primary, Wolpin, Brian M., primary, Schrock, Alexa B., primary, Giannakis, Marios, primary, Ng, Kimmie, primary, Meyerhardt, Jeffrey A., primary, Hornick, Jason L., primary, Sethi, Nilay S., primary, and Cleary, James M., primary

Published
2024
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38. Supplementary Table 8 from RAS/RAF Comutation and ERBB2 Copy Number Modulates HER2 Heterogeneity and Responsiveness to HER2-directed Therapy in Colorectal Cancer

Author

Singh, Harshabad, primary, Sahgal, Pranshu, primary, Kapner, Kevin, primary, Corsello, Steven M., primary, Gupta, Hersh, primary, Gujrathi, Rahul, primary, Li, Yvonne Y., primary, Cherniack, Andrew D., primary, El Alam, Raquelle, primary, Kerfoot, Joseph, primary, Andrews, Elizabeth, primary, Lee, Annette, primary, Nambiar, Chetan, primary, Hannigan, Alison M., primary, Remland, Joshua, primary, Brais, Lauren, primary, Leahy, Meghan E., primary, Rubinson, Douglas A., primary, Schlechter, Benjamin L., primary, Meyerson, Matthew, primary, Kuang, Yanan, primary, Paweletz, Cloud P., primary, Lee, Jessica K., primary, Quintanilha, Julia C.F., primary, Aguirre, Andrew J., primary, Perez, Kimberly J., primary, Huffman, Brandon M., primary, Rossi, Humberto, primary, Abrams, Thomas A., primary, Kabraji, Sheheryar, primary, Trusolino, Livio, primary, Bertotti, Andrea, primary, Sicinska, Ewa T., primary, Parikh, Aparna R., primary, Wolpin, Brian M., primary, Schrock, Alexa B., primary, Giannakis, Marios, primary, Ng, Kimmie, primary, Meyerhardt, Jeffrey A., primary, Hornick, Jason L., primary, Sethi, Nilay S., primary, and Cleary, James M., primary

Published
2024
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39. Supplementary Table 5 from RAS/RAF Comutation and ERBB2 Copy Number Modulates HER2 Heterogeneity and Responsiveness to HER2-directed Therapy in Colorectal Cancer

Author

Singh, Harshabad, primary, Sahgal, Pranshu, primary, Kapner, Kevin, primary, Corsello, Steven M., primary, Gupta, Hersh, primary, Gujrathi, Rahul, primary, Li, Yvonne Y., primary, Cherniack, Andrew D., primary, El Alam, Raquelle, primary, Kerfoot, Joseph, primary, Andrews, Elizabeth, primary, Lee, Annette, primary, Nambiar, Chetan, primary, Hannigan, Alison M., primary, Remland, Joshua, primary, Brais, Lauren, primary, Leahy, Meghan E., primary, Rubinson, Douglas A., primary, Schlechter, Benjamin L., primary, Meyerson, Matthew, primary, Kuang, Yanan, primary, Paweletz, Cloud P., primary, Lee, Jessica K., primary, Quintanilha, Julia C.F., primary, Aguirre, Andrew J., primary, Perez, Kimberly J., primary, Huffman, Brandon M., primary, Rossi, Humberto, primary, Abrams, Thomas A., primary, Kabraji, Sheheryar, primary, Trusolino, Livio, primary, Bertotti, Andrea, primary, Sicinska, Ewa T., primary, Parikh, Aparna R., primary, Wolpin, Brian M., primary, Schrock, Alexa B., primary, Giannakis, Marios, primary, Ng, Kimmie, primary, Meyerhardt, Jeffrey A., primary, Hornick, Jason L., primary, Sethi, Nilay S., primary, and Cleary, James M., primary

Published
2024
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40. Supplementary Figure 5 from RAS/RAF Comutation and ERBB2 Copy Number Modulates HER2 Heterogeneity and Responsiveness to HER2-directed Therapy in Colorectal Cancer

Author

Singh, Harshabad, primary, Sahgal, Pranshu, primary, Kapner, Kevin, primary, Corsello, Steven M., primary, Gupta, Hersh, primary, Gujrathi, Rahul, primary, Li, Yvonne Y., primary, Cherniack, Andrew D., primary, El Alam, Raquelle, primary, Kerfoot, Joseph, primary, Andrews, Elizabeth, primary, Lee, Annette, primary, Nambiar, Chetan, primary, Hannigan, Alison M., primary, Remland, Joshua, primary, Brais, Lauren, primary, Leahy, Meghan E., primary, Rubinson, Douglas A., primary, Schlechter, Benjamin L., primary, Meyerson, Matthew, primary, Kuang, Yanan, primary, Paweletz, Cloud P., primary, Lee, Jessica K., primary, Quintanilha, Julia C.F., primary, Aguirre, Andrew J., primary, Perez, Kimberly J., primary, Huffman, Brandon M., primary, Rossi, Humberto, primary, Abrams, Thomas A., primary, Kabraji, Sheheryar, primary, Trusolino, Livio, primary, Bertotti, Andrea, primary, Sicinska, Ewa T., primary, Parikh, Aparna R., primary, Wolpin, Brian M., primary, Schrock, Alexa B., primary, Giannakis, Marios, primary, Ng, Kimmie, primary, Meyerhardt, Jeffrey A., primary, Hornick, Jason L., primary, Sethi, Nilay S., primary, and Cleary, James M., primary

Published
2024
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41. Supplementary Table 2 from RAS/RAF Comutation and ERBB2 Copy Number Modulates HER2 Heterogeneity and Responsiveness to HER2-directed Therapy in Colorectal Cancer

Author

Singh, Harshabad, primary, Sahgal, Pranshu, primary, Kapner, Kevin, primary, Corsello, Steven M., primary, Gupta, Hersh, primary, Gujrathi, Rahul, primary, Li, Yvonne Y., primary, Cherniack, Andrew D., primary, El Alam, Raquelle, primary, Kerfoot, Joseph, primary, Andrews, Elizabeth, primary, Lee, Annette, primary, Nambiar, Chetan, primary, Hannigan, Alison M., primary, Remland, Joshua, primary, Brais, Lauren, primary, Leahy, Meghan E., primary, Rubinson, Douglas A., primary, Schlechter, Benjamin L., primary, Meyerson, Matthew, primary, Kuang, Yanan, primary, Paweletz, Cloud P., primary, Lee, Jessica K., primary, Quintanilha, Julia C.F., primary, Aguirre, Andrew J., primary, Perez, Kimberly J., primary, Huffman, Brandon M., primary, Rossi, Humberto, primary, Abrams, Thomas A., primary, Kabraji, Sheheryar, primary, Trusolino, Livio, primary, Bertotti, Andrea, primary, Sicinska, Ewa T., primary, Parikh, Aparna R., primary, Wolpin, Brian M., primary, Schrock, Alexa B., primary, Giannakis, Marios, primary, Ng, Kimmie, primary, Meyerhardt, Jeffrey A., primary, Hornick, Jason L., primary, Sethi, Nilay S., primary, and Cleary, James M., primary

Published
2024
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42. Supplementary Table 9 from RAS/RAF Comutation and ERBB2 Copy Number Modulates HER2 Heterogeneity and Responsiveness to HER2-directed Therapy in Colorectal Cancer

Author

Singh, Harshabad, primary, Sahgal, Pranshu, primary, Kapner, Kevin, primary, Corsello, Steven M., primary, Gupta, Hersh, primary, Gujrathi, Rahul, primary, Li, Yvonne Y., primary, Cherniack, Andrew D., primary, El Alam, Raquelle, primary, Kerfoot, Joseph, primary, Andrews, Elizabeth, primary, Lee, Annette, primary, Nambiar, Chetan, primary, Hannigan, Alison M., primary, Remland, Joshua, primary, Brais, Lauren, primary, Leahy, Meghan E., primary, Rubinson, Douglas A., primary, Schlechter, Benjamin L., primary, Meyerson, Matthew, primary, Kuang, Yanan, primary, Paweletz, Cloud P., primary, Lee, Jessica K., primary, Quintanilha, Julia C.F., primary, Aguirre, Andrew J., primary, Perez, Kimberly J., primary, Huffman, Brandon M., primary, Rossi, Humberto, primary, Abrams, Thomas A., primary, Kabraji, Sheheryar, primary, Trusolino, Livio, primary, Bertotti, Andrea, primary, Sicinska, Ewa T., primary, Parikh, Aparna R., primary, Wolpin, Brian M., primary, Schrock, Alexa B., primary, Giannakis, Marios, primary, Ng, Kimmie, primary, Meyerhardt, Jeffrey A., primary, Hornick, Jason L., primary, Sethi, Nilay S., primary, and Cleary, James M., primary

Published
2024
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43. Supplementary Table 7 from RAS/RAF Comutation and ERBB2 Copy Number Modulates HER2 Heterogeneity and Responsiveness to HER2-directed Therapy in Colorectal Cancer

Author

Singh, Harshabad, primary, Sahgal, Pranshu, primary, Kapner, Kevin, primary, Corsello, Steven M., primary, Gupta, Hersh, primary, Gujrathi, Rahul, primary, Li, Yvonne Y., primary, Cherniack, Andrew D., primary, El Alam, Raquelle, primary, Kerfoot, Joseph, primary, Andrews, Elizabeth, primary, Lee, Annette, primary, Nambiar, Chetan, primary, Hannigan, Alison M., primary, Remland, Joshua, primary, Brais, Lauren, primary, Leahy, Meghan E., primary, Rubinson, Douglas A., primary, Schlechter, Benjamin L., primary, Meyerson, Matthew, primary, Kuang, Yanan, primary, Paweletz, Cloud P., primary, Lee, Jessica K., primary, Quintanilha, Julia C.F., primary, Aguirre, Andrew J., primary, Perez, Kimberly J., primary, Huffman, Brandon M., primary, Rossi, Humberto, primary, Abrams, Thomas A., primary, Kabraji, Sheheryar, primary, Trusolino, Livio, primary, Bertotti, Andrea, primary, Sicinska, Ewa T., primary, Parikh, Aparna R., primary, Wolpin, Brian M., primary, Schrock, Alexa B., primary, Giannakis, Marios, primary, Ng, Kimmie, primary, Meyerhardt, Jeffrey A., primary, Hornick, Jason L., primary, Sethi, Nilay S., primary, and Cleary, James M., primary

Published
2024
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44. Supplementary Figure 6 from RAS/RAF Comutation and ERBB2 Copy Number Modulates HER2 Heterogeneity and Responsiveness to HER2-directed Therapy in Colorectal Cancer

Author

Singh, Harshabad, primary, Sahgal, Pranshu, primary, Kapner, Kevin, primary, Corsello, Steven M., primary, Gupta, Hersh, primary, Gujrathi, Rahul, primary, Li, Yvonne Y., primary, Cherniack, Andrew D., primary, El Alam, Raquelle, primary, Kerfoot, Joseph, primary, Andrews, Elizabeth, primary, Lee, Annette, primary, Nambiar, Chetan, primary, Hannigan, Alison M., primary, Remland, Joshua, primary, Brais, Lauren, primary, Leahy, Meghan E., primary, Rubinson, Douglas A., primary, Schlechter, Benjamin L., primary, Meyerson, Matthew, primary, Kuang, Yanan, primary, Paweletz, Cloud P., primary, Lee, Jessica K., primary, Quintanilha, Julia C.F., primary, Aguirre, Andrew J., primary, Perez, Kimberly J., primary, Huffman, Brandon M., primary, Rossi, Humberto, primary, Abrams, Thomas A., primary, Kabraji, Sheheryar, primary, Trusolino, Livio, primary, Bertotti, Andrea, primary, Sicinska, Ewa T., primary, Parikh, Aparna R., primary, Wolpin, Brian M., primary, Schrock, Alexa B., primary, Giannakis, Marios, primary, Ng, Kimmie, primary, Meyerhardt, Jeffrey A., primary, Hornick, Jason L., primary, Sethi, Nilay S., primary, and Cleary, James M., primary

Published
2024
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45. Supplementary Table 3 from RAS/RAF Comutation and ERBB2 Copy Number Modulates HER2 Heterogeneity and Responsiveness to HER2-directed Therapy in Colorectal Cancer

Author

Singh, Harshabad, primary, Sahgal, Pranshu, primary, Kapner, Kevin, primary, Corsello, Steven M., primary, Gupta, Hersh, primary, Gujrathi, Rahul, primary, Li, Yvonne Y., primary, Cherniack, Andrew D., primary, El Alam, Raquelle, primary, Kerfoot, Joseph, primary, Andrews, Elizabeth, primary, Lee, Annette, primary, Nambiar, Chetan, primary, Hannigan, Alison M., primary, Remland, Joshua, primary, Brais, Lauren, primary, Leahy, Meghan E., primary, Rubinson, Douglas A., primary, Schlechter, Benjamin L., primary, Meyerson, Matthew, primary, Kuang, Yanan, primary, Paweletz, Cloud P., primary, Lee, Jessica K., primary, Quintanilha, Julia C.F., primary, Aguirre, Andrew J., primary, Perez, Kimberly J., primary, Huffman, Brandon M., primary, Rossi, Humberto, primary, Abrams, Thomas A., primary, Kabraji, Sheheryar, primary, Trusolino, Livio, primary, Bertotti, Andrea, primary, Sicinska, Ewa T., primary, Parikh, Aparna R., primary, Wolpin, Brian M., primary, Schrock, Alexa B., primary, Giannakis, Marios, primary, Ng, Kimmie, primary, Meyerhardt, Jeffrey A., primary, Hornick, Jason L., primary, Sethi, Nilay S., primary, and Cleary, James M., primary

Published
2024
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46. Supplementary Methods 1 from RAS/RAF Comutation and ERBB2 Copy Number Modulates HER2 Heterogeneity and Responsiveness to HER2-directed Therapy in Colorectal Cancer

Author

Singh, Harshabad, primary, Sahgal, Pranshu, primary, Kapner, Kevin, primary, Corsello, Steven M., primary, Gupta, Hersh, primary, Gujrathi, Rahul, primary, Li, Yvonne Y., primary, Cherniack, Andrew D., primary, El Alam, Raquelle, primary, Kerfoot, Joseph, primary, Andrews, Elizabeth, primary, Lee, Annette, primary, Nambiar, Chetan, primary, Hannigan, Alison M., primary, Remland, Joshua, primary, Brais, Lauren, primary, Leahy, Meghan E., primary, Rubinson, Douglas A., primary, Schlechter, Benjamin L., primary, Meyerson, Matthew, primary, Kuang, Yanan, primary, Paweletz, Cloud P., primary, Lee, Jessica K., primary, Quintanilha, Julia C.F., primary, Aguirre, Andrew J., primary, Perez, Kimberly J., primary, Huffman, Brandon M., primary, Rossi, Humberto, primary, Abrams, Thomas A., primary, Kabraji, Sheheryar, primary, Trusolino, Livio, primary, Bertotti, Andrea, primary, Sicinska, Ewa T., primary, Parikh, Aparna R., primary, Wolpin, Brian M., primary, Schrock, Alexa B., primary, Giannakis, Marios, primary, Ng, Kimmie, primary, Meyerhardt, Jeffrey A., primary, Hornick, Jason L., primary, Sethi, Nilay S., primary, and Cleary, James M., primary

Published
2024
Full Text
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47. Supplementary Figure 3 from RAS/RAF Comutation and ERBB2 Copy Number Modulates HER2 Heterogeneity and Responsiveness to HER2-directed Therapy in Colorectal Cancer

Author

Singh, Harshabad, primary, Sahgal, Pranshu, primary, Kapner, Kevin, primary, Corsello, Steven M., primary, Gupta, Hersh, primary, Gujrathi, Rahul, primary, Li, Yvonne Y., primary, Cherniack, Andrew D., primary, El Alam, Raquelle, primary, Kerfoot, Joseph, primary, Andrews, Elizabeth, primary, Lee, Annette, primary, Nambiar, Chetan, primary, Hannigan, Alison M., primary, Remland, Joshua, primary, Brais, Lauren, primary, Leahy, Meghan E., primary, Rubinson, Douglas A., primary, Schlechter, Benjamin L., primary, Meyerson, Matthew, primary, Kuang, Yanan, primary, Paweletz, Cloud P., primary, Lee, Jessica K., primary, Quintanilha, Julia C.F., primary, Aguirre, Andrew J., primary, Perez, Kimberly J., primary, Huffman, Brandon M., primary, Rossi, Humberto, primary, Abrams, Thomas A., primary, Kabraji, Sheheryar, primary, Trusolino, Livio, primary, Bertotti, Andrea, primary, Sicinska, Ewa T., primary, Parikh, Aparna R., primary, Wolpin, Brian M., primary, Schrock, Alexa B., primary, Giannakis, Marios, primary, Ng, Kimmie, primary, Meyerhardt, Jeffrey A., primary, Hornick, Jason L., primary, Sethi, Nilay S., primary, and Cleary, James M., primary

Published
2024
Full Text
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48. Supplementary Table 6 from RAS/RAF Comutation and ERBB2 Copy Number Modulates HER2 Heterogeneity and Responsiveness to HER2-directed Therapy in Colorectal Cancer

Author

Singh, Harshabad, primary, Sahgal, Pranshu, primary, Kapner, Kevin, primary, Corsello, Steven M., primary, Gupta, Hersh, primary, Gujrathi, Rahul, primary, Li, Yvonne Y., primary, Cherniack, Andrew D., primary, El Alam, Raquelle, primary, Kerfoot, Joseph, primary, Andrews, Elizabeth, primary, Lee, Annette, primary, Nambiar, Chetan, primary, Hannigan, Alison M., primary, Remland, Joshua, primary, Brais, Lauren, primary, Leahy, Meghan E., primary, Rubinson, Douglas A., primary, Schlechter, Benjamin L., primary, Meyerson, Matthew, primary, Kuang, Yanan, primary, Paweletz, Cloud P., primary, Lee, Jessica K., primary, Quintanilha, Julia C.F., primary, Aguirre, Andrew J., primary, Perez, Kimberly J., primary, Huffman, Brandon M., primary, Rossi, Humberto, primary, Abrams, Thomas A., primary, Kabraji, Sheheryar, primary, Trusolino, Livio, primary, Bertotti, Andrea, primary, Sicinska, Ewa T., primary, Parikh, Aparna R., primary, Wolpin, Brian M., primary, Schrock, Alexa B., primary, Giannakis, Marios, primary, Ng, Kimmie, primary, Meyerhardt, Jeffrey A., primary, Hornick, Jason L., primary, Sethi, Nilay S., primary, and Cleary, James M., primary

Published
2024
Full Text
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49. Supplementary Figure 2 from RAS/RAF Comutation and ERBB2 Copy Number Modulates HER2 Heterogeneity and Responsiveness to HER2-directed Therapy in Colorectal Cancer

Author

Singh, Harshabad, primary, Sahgal, Pranshu, primary, Kapner, Kevin, primary, Corsello, Steven M., primary, Gupta, Hersh, primary, Gujrathi, Rahul, primary, Li, Yvonne Y., primary, Cherniack, Andrew D., primary, El Alam, Raquelle, primary, Kerfoot, Joseph, primary, Andrews, Elizabeth, primary, Lee, Annette, primary, Nambiar, Chetan, primary, Hannigan, Alison M., primary, Remland, Joshua, primary, Brais, Lauren, primary, Leahy, Meghan E., primary, Rubinson, Douglas A., primary, Schlechter, Benjamin L., primary, Meyerson, Matthew, primary, Kuang, Yanan, primary, Paweletz, Cloud P., primary, Lee, Jessica K., primary, Quintanilha, Julia C.F., primary, Aguirre, Andrew J., primary, Perez, Kimberly J., primary, Huffman, Brandon M., primary, Rossi, Humberto, primary, Abrams, Thomas A., primary, Kabraji, Sheheryar, primary, Trusolino, Livio, primary, Bertotti, Andrea, primary, Sicinska, Ewa T., primary, Parikh, Aparna R., primary, Wolpin, Brian M., primary, Schrock, Alexa B., primary, Giannakis, Marios, primary, Ng, Kimmie, primary, Meyerhardt, Jeffrey A., primary, Hornick, Jason L., primary, Sethi, Nilay S., primary, and Cleary, James M., primary

Published
2024
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50. Supplementary Table 4 from RAS/RAF Comutation and ERBB2 Copy Number Modulates HER2 Heterogeneity and Responsiveness to HER2-directed Therapy in Colorectal Cancer

Author

Singh, Harshabad, primary, Sahgal, Pranshu, primary, Kapner, Kevin, primary, Corsello, Steven M., primary, Gupta, Hersh, primary, Gujrathi, Rahul, primary, Li, Yvonne Y., primary, Cherniack, Andrew D., primary, El Alam, Raquelle, primary, Kerfoot, Joseph, primary, Andrews, Elizabeth, primary, Lee, Annette, primary, Nambiar, Chetan, primary, Hannigan, Alison M., primary, Remland, Joshua, primary, Brais, Lauren, primary, Leahy, Meghan E., primary, Rubinson, Douglas A., primary, Schlechter, Benjamin L., primary, Meyerson, Matthew, primary, Kuang, Yanan, primary, Paweletz, Cloud P., primary, Lee, Jessica K., primary, Quintanilha, Julia C.F., primary, Aguirre, Andrew J., primary, Perez, Kimberly J., primary, Huffman, Brandon M., primary, Rossi, Humberto, primary, Abrams, Thomas A., primary, Kabraji, Sheheryar, primary, Trusolino, Livio, primary, Bertotti, Andrea, primary, Sicinska, Ewa T., primary, Parikh, Aparna R., primary, Wolpin, Brian M., primary, Schrock, Alexa B., primary, Giannakis, Marios, primary, Ng, Kimmie, primary, Meyerhardt, Jeffrey A., primary, Hornick, Jason L., primary, Sethi, Nilay S., primary, and Cleary, James M., primary

Published
2024
Full Text
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