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1. Therapy-induced APOBEC3A drives evolution of persistent cancer cells

Author

Isozaki, Hideko, Sakhtemani, Ramin, Abbasi, Ammal, Nikpour, Naveed, Stanzione, Marcello, Oh, Sunwoo, Langenbucher, Adam, Monroe, Susanna, Su, Wenjia, Cabanos, Heidie Frisco, Siddiqui, Faria M, Phan, Nicole, Jalili, Pégah, Timonina, Daria, Bilton, Samantha, Gomez-Caraballo, Maria, Archibald, Hannah L, Nangia, Varuna, Dionne, Kristin, Riley, Amanda, Lawlor, Matthew, Banwait, Mandeep Kaur, Cobb, Rosemary G, Zou, Lee, Dyson, Nicholas J, Ott, Christopher J, Benes, Cyril, Getz, Gad, Chan, Chang S, Shaw, Alice T, Gainor, Justin F, Lin, Jessica J, Sequist, Lecia V, Piotrowska, Zofia, Yeap, Beow Y, Engelman, Jeffrey A, Lee, Jake June-Koo, Maruvka, Yosef E, Buisson, Rémi, Lawrence, Michael S, and Hata, Aaron N

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Genetics, Lung Cancer, Cancer, Lung, Aetiology, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, 2.1 Biological and endogenous factors, Good Health and Well Being, Humans, Cytidine Deaminase, DNA Breaks, Double-Stranded, Genomic Instability, Lung Neoplasms, Molecular Targeted Therapy, Mutation, Drug Resistance, Neoplasm, General Science & Technology
Abstract

Acquired drug resistance to anticancer targeted therapies remains an unsolved clinical problem. Although many drivers of acquired drug resistance have been identified1-4, the underlying molecular mechanisms shaping tumour evolution during treatment are incompletely understood. Genomic profiling of patient tumours has implicated apolipoprotein B messenger RNA editing catalytic polypeptide-like (APOBEC) cytidine deaminases in tumour evolution; however, their role during therapy and the development of acquired drug resistance is undefined. Here we report that lung cancer targeted therapies commonly used in the clinic can induce cytidine deaminase APOBEC3A (A3A), leading to sustained mutagenesis in drug-tolerant cancer cells persisting during therapy. Therapy-induced A3A promotes the formation of double-strand DNA breaks, increasing genomic instability in drug-tolerant persisters. Deletion of A3A reduces APOBEC mutations and structural variations in persister cells and delays the development of drug resistance. APOBEC mutational signatures are enriched in tumours from patients with lung cancer who progressed after extended responses to targeted therapies. This study shows that induction of A3A in response to targeted therapies drives evolution of drug-tolerant persister cells, suggesting that suppression of A3A expression or activity may represent a potential therapeutic strategy in the prevention or delay of acquired resistance to lung cancer targeted therapy.

Published
2023

2. Analyses of non-coding somatic drivers in 2,658 cancer whole genomes.

Author

Rheinbay, Esther, Nielsen, Morten Muhlig, Abascal, Federico, Wala, Jeremiah A, Shapira, Ofer, Tiao, Grace, Hornshøj, Henrik, Hess, Julian M, Juul, Randi Istrup, Lin, Ziao, Feuerbach, Lars, Sabarinathan, Radhakrishnan, Madsen, Tobias, Kim, Jaegil, Mularoni, Loris, Shuai, Shimin, Lanzós, Andrés, Herrmann, Carl, Maruvka, Yosef E, Shen, Ciyue, Amin, Samirkumar B, Bandopadhayay, Pratiti, Bertl, Johanna, Boroevich, Keith A, Busanovich, John, Carlevaro-Fita, Joana, Chakravarty, Dimple, Chan, Calvin Wing Yiu, Craft, David, Dhingra, Priyanka, Diamanti, Klev, Fonseca, Nuno A, Gonzalez-Perez, Abel, Guo, Qianyun, Hamilton, Mark P, Haradhvala, Nicholas J, Hong, Chen, Isaev, Keren, Johnson, Todd A, Juul, Malene, Kahles, Andre, Kahraman, Abdullah, Kim, Youngwook, Komorowski, Jan, Kumar, Kiran, Kumar, Sushant, Lee, Donghoon, Lehmann, Kjong-Van, Li, Yilong, Liu, Eric Minwei, Lochovsky, Lucas, Park, Keunchil, Pich, Oriol, Roberts, Nicola D, Saksena, Gordon, Schumacher, Steven E, Sidiropoulos, Nikos, Sieverling, Lina, Sinnott-Armstrong, Nasa, Stewart, Chip, Tamborero, David, Tubio, Jose MC, Umer, Husen M, Uusküla-Reimand, Liis, Wadelius, Claes, Wadi, Lina, Yao, Xiaotong, Zhang, Cheng-Zhong, Zhang, Jing, Haber, James E, Hobolth, Asger, Imielinski, Marcin, Kellis, Manolis, Lawrence, Michael S, von Mering, Christian, Nakagawa, Hidewaki, Raphael, Benjamin J, Rubin, Mark A, Sander, Chris, Stein, Lincoln D, Stuart, Joshua M, Tsunoda, Tatsuhiko, Wheeler, David A, Johnson, Rory, Reimand, Jüri, Gerstein, Mark, Khurana, Ekta, Campbell, Peter J, López-Bigas, Núria, PCAWG Drivers and Functional Interpretation Working Group, PCAWG Structural Variation Working Group, Weischenfeldt, Joachim, Beroukhim, Rameen, Martincorena, Iñigo, Pedersen, Jakob Skou, Getz, Gad, and PCAWG Consortium

Subjects
PCAWG Drivers and Functional Interpretation Working Group, PCAWG Structural Variation Working Group, PCAWG Consortium, Humans, Neoplasms, Gene Expression Regulation, Neoplastic, Mutation, Genome, Human, Databases, Genetic, DNA Breaks, INDEL Mutation, Genome-Wide Association Study, Gene Expression Regulation, Neoplastic, Genome, Human, Databases, Genetic, General Science & Technology
Abstract

The discovery of drivers of cancer has traditionally focused on protein-coding genes1-4. Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658 genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium5 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). For point mutations, we developed a statistically rigorous strategy for combining significance levels from multiple methods of driver discovery that overcomes the limitations of individual methods. For structural variants, we present two methods of driver discovery, and identify regions that are significantly affected by recurrent breakpoints and recurrent somatic juxtapositions. Our analyses confirm previously reported drivers6,7, raise doubts about others and identify novel candidates, including point mutations in the 5' region of TP53, in the 3' untranslated regions of NFKBIZ and TOB1, focal deletions in BRD4 and rearrangements in the loci of AKR1C genes. We show that although point mutations and structural variants that drive cancer are less frequent in non-coding genes and regulatory sequences than in protein-coding genes, additional examples of these drivers will be found as more cancer genomes become available.

Published
2020

3. 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

4. Comprehensive genomic characterization of head and neck squamous cell carcinomas

Author

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

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

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

Published
2015

5. Comprehensive molecular characterization of gastric adenocarcinoma

Author

Bass, Adam J, Thorsson, Vesteinn, Shmulevich, Ilya, Reynolds, Sheila M, Miller, Michael, Bernard, Brady, Hinoue, Toshinori, Laird, Peter W, Curtis, Christina, Shen, Hui, Weisenberger, Daniel J, Schultz, Nikolaus, Shen, Ronglai, Weinhold, Nils, Kelsen, David P, Bowlby, Reanne, Chu, Andy, Kasaian, Katayoon, Mungall, Andrew J, Robertson, A Gordon, Sipahimalani, Payal, Cherniack, Andrew, Getz, Gad, Liu, Yingchun, Noble, Michael S, Pedamallu, Chandra, Sougnez, Carrie, Taylor-Weiner, Amaro, Akbani, Rehan, Lee, Ju-Seog, Liu, Wenbin, Mills, Gordon B, Yang, Da, Zhang, Wei, Pantazi, Angeliki, Parfenov, Michael, Gulley, Margaret, Piazuelo, M Blanca, Schneider, Barbara G, Kim, Jihun, Boussioutas, Alex, Sheth, Margi, Demchok, John A, Rabkin, Charles S, Willis, Joseph E, Ng, Sam, Garman, Katherine, Beer, David G, Pennathur, Arjun, Raphael, Benjamin J, Wu, Hsin-Ta, Odze, Robert, Kim, Hark K, Bowen, Jay, Leraas, Kristen M, Lichtenberg, Tara M, Weaver, Stephanie, McLellan, Michael, Wiznerowicz, Maciej, Sakai, Ryo, Lawrence, Michael S, Cibulskis, Kristian, Lichtenstein, Lee, Fisher, Sheila, Gabriel, Stacey B, Lander, Eric S, Ding, Li, Niu, Beifang, Ally, Adrian, Balasundaram, Miruna, Birol, Inanc, Brooks, Denise, Butterfield, Yaron SN, Carlsen, Rebecca, Chu, Justin, Chuah, Eric, Chun, Hye-Jung E, Clarke, Amanda, Dhalla, Noreen, Guin, Ranabir, Holt, Robert A, Jones, Steven JM, Lee, Darlene, Li, Haiyan A, Lim, Emilia, Ma, Yussanne, Marra, Marco A, Mayo, Michael, Moore, Richard A, Mungall, Karen L, Ming Nip, Ka, and Schein, Jacqueline E

Subjects
Genetics, Digestive Diseases, Genetic Testing, Human Genome, Rare Diseases, Cancer, Good Health and Well Being, Adenocarcinoma, Female, Gene Expression Regulation, Neoplastic, Genome, Human, Herpesvirus 4, Human, Humans, Male, Mutation, Proteome, Stomach Neoplasms, Cancer Genome Atlas Research Network, General Science & Technology
Abstract

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

Published
2014

6. Comprehensive molecular profiling of lung adenocarcinoma

Author

Collisson, Eric A, Campbell, Joshua D, Brooks, Angela N, Berger, Alice H, Lee, William, Chmielecki, Juliann, Beer, David G, Cope, Leslie, Creighton, Chad J, Danilova, Ludmila, Ding, Li, Getz, Gad, Hammerman, Peter S, Neil Hayes, D, Hernandez, Bryan, Herman, James G, Heymach, John V, Jurisica, Igor, Kucherlapati, Raju, Kwiatkowski, David, Ladanyi, Marc, Robertson, Gordon, Schultz, Nikolaus, Shen, Ronglai, Sinha, Rileen, Sougnez, Carrie, Tsao, Ming-Sound, Travis, William D, Weinstein, John N, Wigle, Dennis A, Wilkerson, Matthew D, Chu, Andy, Cherniack, Andrew D, Hadjipanayis, Angela, Rosenberg, Mara, Weisenberger, Daniel J, Laird, Peter W, Radenbaugh, Amie, Ma, Singer, Stuart, Joshua M, Averett Byers, Lauren, Baylin, Stephen B, Govindan, Ramaswamy, Meyerson, Matthew, Gabriel, Stacey B, Cibulskis, Kristian, Kim, Jaegil, Stewart, Chip, Lichtenstein, Lee, Lander, Eric S, Lawrence, Michael S, Kandoth, Cyriac, Fulton, Robert, Fulton, Lucinda L, McLellan, Michael D, Wilson, Richard K, Ye, Kai, Fronick, Catrina C, Maher, Christopher A, Miller, Christopher A, Wendl, Michael C, Cabanski, Christopher, Mardis, Elaine, Wheeler, David, Balasundaram, Miruna, Butterfield, Yaron SN, Carlsen, Rebecca, Chuah, Eric, Dhalla, Noreen, Guin, Ranabir, Hirst, Carrie, Lee, Darlene, Li, Haiyan I, Mayo, Michael, Moore, Richard A, Mungall, Andrew J, Schein, Jacqueline E, Sipahimalani, Payal, Tam, Angela, Varhol, Richard, Gordon Robertson, A, Wye, Natasja, Thiessen, Nina, Holt, Robert A, Jones, Steven JM, Marra, Marco A, Imielinski, Marcin, Onofrio, Robert C, Hodis, Eran, and Zack, Travis

Subjects
Rare Diseases, Genetics, Biotechnology, Clinical Research, Lung Cancer, Human Genome, Cancer, Lung, Aetiology, 2.1 Biological and endogenous factors, Adenocarcinoma, Adenocarcinoma of Lung, Cell Cycle Proteins, Female, Gene Dosage, Gene Expression Regulation, Neoplastic, Genomics, Humans, Lung Neoplasms, Male, Molecular Typing, Mutation, Oncogenes, Sex Factors, Transcriptome, Cancer Genome Atlas Research Network, General Science & Technology
Abstract

Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis.

Published
2014

7. Comprehensive genomic characterization of squamous cell lung cancers

Author

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

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

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

Published
2012

8. Medulloblastoma exome sequencing uncovers subtype-specific somatic mutations.

Author

Pugh, Trevor J, Weeraratne, Shyamal Dilhan, Archer, Tenley C, Pomeranz Krummel, Daniel A, Auclair, Daniel, Bochicchio, James, Carneiro, Mauricio O, Carter, Scott L, Cibulskis, Kristian, Erlich, Rachel L, Greulich, Heidi, Lawrence, Michael S, Lennon, Niall J, McKenna, Aaron, Meldrim, James, Ramos, Alex H, Ross, Michael G, Russ, Carsten, Shefler, Erica, Sivachenko, Andrey, Sogoloff, Brian, Stojanov, Petar, Tamayo, Pablo, Mesirov, Jill P, Amani, Vladimir, Teider, Natalia, Sengupta, Soma, Francois, Jessica Pierre, Northcott, Paul A, Taylor, Michael D, Yu, Furong, Crabtree, Gerald R, Kautzman, Amanda G, Gabriel, Stacey B, Getz, Gad, Jäger, Natalie, Jones, David TW, Lichter, Peter, Pfister, Stefan M, Roberts, Thomas M, Meyerson, Matthew, Pomeroy, Scott L, and Cho, Yoon-Jae

Subjects
Humans, Medulloblastoma, Cerebellar Neoplasms, DNA Helicases, Histone-Lysine N-Methyltransferase, Intracellular Signaling Peptides and Proteins, DNA-Binding Proteins, Receptors, Cell Surface, Neoplasm Proteins, Proto-Oncogene Proteins, Nuclear Proteins, Transcription Factors, Repressor Proteins, Signal Transduction, Protein Structure, Tertiary, Mutation, Genome, Human, Models, Molecular, Child, Tumor Suppressor Protein p53, Wnt Proteins, beta Catenin, TCF Transcription Factors, Hedgehog Proteins, DEAD-box RNA Helicases, Promoter Regions, Genetic, LIM Domain Proteins, Exome, Patched Receptors, Patched-1 Receptor, Histone Methyltransferases, Brain Disorders, Pediatric Cancer, Cancer, Human Genome, Biotechnology, Pediatric, Brain Cancer, Rare Diseases, Genetics, Neurosciences, Genetic Testing, Aetiology, 2.1 Biological and endogenous factors, General Science & Technology
Abstract

Medulloblastomas are the most common malignant brain tumours in children. Identifying and understanding the genetic events that drive these tumours is critical for the development of more effective diagnostic, prognostic and therapeutic strategies. Recently, our group and others described distinct molecular subtypes of medulloblastoma on the basis of transcriptional and copy number profiles. Here we use whole-exome hybrid capture and deep sequencing to identify somatic mutations across the coding regions of 92 primary medulloblastoma/normal pairs. Overall, medulloblastomas have low mutation rates consistent with other paediatric tumours, with a median of 0.35 non-silent mutations per megabase. We identified twelve genes mutated at statistically significant frequencies, including previously known mutated genes in medulloblastoma such as CTNNB1, PTCH1, MLL2, SMARCA4 and TP53. Recurrent somatic mutations were newly identified in an RNA helicase gene, DDX3X, often concurrent with CTNNB1 mutations, and in the nuclear co-repressor (N-CoR) complex genes GPS2, BCOR and LDB1. We show that mutant DDX3X potentiates transactivation of a TCF promoter and enhances cell viability in combination with mutant, but not wild-type, β-catenin. Together, our study reveals the alteration of WNT, hedgehog, histone methyltransferase and now N-CoR pathways across medulloblastomas and within specific subtypes of this disease, and nominates the RNA helicase DDX3X as a component of pathogenic β-catenin signalling in medulloblastoma.

Published
2012

9. Comprehensive genomic characterization defines human glioblastoma genes and core pathways

Author

McLendon, Roger, Friedman, Allan, Bigner, Darrell, Van Meir, Erwin G, Brat, Daniel J, M. Mastrogianakis, Gena, Olson, Jeffrey J, Mikkelsen, Tom, Lehman, Norman, Aldape, Ken, Alfred Yung, WK, Bogler, Oliver, VandenBerg, Scott, Berger, Mitchel, Prados, Michael, Muzny, Donna, Morgan, Margaret, Scherer, Steve, Sabo, Aniko, Nazareth, Lynn, Lewis, Lora, Hall, Otis, Zhu, Yiming, Ren, Yanru, Alvi, Omar, Yao, Jiqiang, Hawes, Alicia, Jhangiani, Shalini, Fowler, Gerald, San Lucas, Anthony, Kovar, Christie, Cree, Andrew, Dinh, Huyen, Santibanez, Jireh, Joshi, Vandita, Gonzalez-Garay, Manuel L, Miller, Christopher A, Milosavljevic, Aleksandar, Donehower, Larry, Wheeler, David A, Gibbs, Richard A, Cibulskis, Kristian, Sougnez, Carrie, Fennell, Tim, Mahan, Scott, Wilkinson, Jane, Ziaugra, Liuda, Onofrio, Robert, Bloom, Toby, Nicol, Rob, Ardlie, Kristin, Baldwin, Jennifer, Gabriel, Stacey, Lander, Eric S, Ding, Li, Fulton, Robert S, McLellan, Michael D, Wallis, John, Larson, David E, Shi, Xiaoqi, Abbott, Rachel, Fulton, Lucinda, Chen, Ken, Koboldt, Daniel C, Wendl, Michael C, Meyer, Rick, Tang, Yuzhu, Lin, Ling, Osborne, John R, Dunford-Shore, Brian H, Miner, Tracie L, Delehaunty, Kim, Markovic, Chris, Swift, Gary, Courtney, William, Pohl, Craig, Abbott, Scott, Hawkins, Amy, Leong, Shin, Haipek, Carrie, Schmidt, Heather, Wiechert, Maddy, Vickery, Tammi, Scott, Sacha, Dooling, David J, Chinwalla, Asif, Weinstock, George M, Mardis, Elaine R, Wilson, Richard K, Getz, Gad, Winckler, Wendy, Verhaak, Roel GW, Lawrence, Michael S, O’Kelly, Michael, Robinson, Jim, Alexe, Gabriele, Beroukhim, Rameen, Carter, Scott, Chiang, Derek, and Gould, Josh

Subjects
Cancer, Human Genome, Genetic Testing, Brain Cancer, Genetics, Brain Disorders, Biotechnology, Rare Diseases, Aetiology, 2.1 Biological and endogenous factors, Adolescent, Adult, Aged, Aged, 80 and over, Brain Neoplasms, DNA Methylation, DNA Modification Methylases, DNA Repair, DNA Repair Enzymes, Female, Gene Dosage, Gene Expression Regulation, Neoplastic, Genes, Tumor Suppressor, Genes, erbB-1, Genome, Human, Genomics, Glioblastoma, Humans, Male, Middle Aged, Models, Molecular, Mutation, Neurofibromin 1, Phosphatidylinositol 3-Kinases, Protein Structure, Tertiary, Retrospective Studies, Signal Transduction, Tumor Suppressor Proteins, Cancer Genome Atlas Research Network, General Science & Technology
Abstract

Human cancer cells typically harbour multiple chromosomal aberrations, nucleotide substitutions and epigenetic modifications that drive malignant transformation. The Cancer Genome Atlas (TCGA) pilot project aims to assess the value of large-scale multi-dimensional analysis of these molecular characteristics in human cancer and to provide the data rapidly to the research community. Here we report the interim integrative analysis of DNA copy number, gene expression and DNA methylation aberrations in 206 glioblastomas--the most common type of adult brain cancer--and nucleotide sequence aberrations in 91 of the 206 glioblastomas. This analysis provides new insights into the roles of ERBB2, NF1 and TP53, uncovers frequent mutations of the phosphatidylinositol-3-OH kinase regulatory subunit gene PIK3R1, and provides a network view of the pathways altered in the development of glioblastoma. Furthermore, integration of mutation, DNA methylation and clinical treatment data reveals a link between MGMT promoter methylation and a hypermutator phenotype consequent to mismatch repair deficiency in treated glioblastomas, an observation with potential clinical implications. Together, these findings establish the feasibility and power of TCGA, demonstrating that it can rapidly expand knowledge of the molecular basis of cancer.

Published
2008

10. Integrated genomic and molecular characterization of cervical cancer

Author

Burk, Robert D., Chen, Zigui, Saller, Charles, Tarvin, Katherine, Carvalho, Andre L., Scapulatempo-Neto, Cristovam, Silveira, Henrique C., Fregnani, Jos H., Creighton, Chad J., Anderson, Matthew L., Castro, Patricia, Wang, Sophia S., Yau, Christina, Benz, Christopher, Robertson, A. Gordon, Mungall, Karen, Lim, Lynette, Bowlby, Reanne, Sadeghi, Sara, Brooks, Denise, Sipahimalani, Payal, Mar, Richard, Ally, Adrian, Clarke, Amanda, Mungall, Andrew J., Tam, Angela, Lee, Darlene, Chuah, Eric, Schein, Jacqueline E., Tse, Kane, Kasaian, Katayoon, Ma, Yussanne, Marra, Marco A., Mayo, Michael, Balasundaram, Miruna, Thiessen, Nina, Dhalla, Noreen, Carlsen, Rebecca, Moore, Richard A., Holt, Robert A., Jones, Steven J. M., Wong, Tina, Pantazi, Angeliki, Parfenov, Michael, Kucherlapati, Raju, Hadjipanayis, Angela, Seidman, Jonathan, Kucherlapati, Melanie, Ren, Xiaojia, Xu, Andrew W., Yang, Lixing, Park, Peter J., Lee, Semin, Rabeno, Brenda, Huelsenbeck-Dill, Lori, Borowsky, Mark, Cadungog, Mark, Iacocca, Mary, Petrelli, Nicholas, Swanson, Patricia, Ojesina, Akinyemi I., Le, Xuan, Sandusky, George, Adebamowo, Sally N., Akeredolu, Teniola, Adebamowo, Clement, Reynolds, Sheila M., Shmulevich, Ilya, Shelton, Candace, Crain, Daniel, Mallery, David, Curley, Erin, Gardner, Johanna, Penny, Robert, Morris, Scott, Shelton, Troy, Liu, Jia, Lolla, Laxmi, Chudamani, Sudha, Wu, Ye, Birrer, Michael, McLellan, Michael D., Bailey, Matthew H., Miller, Christopher A., Wyczalkowski, Matthew A., Fulton, Robert S., Fronick, Catrina C., Lu, Charles, Mardis, Elaine R., Appelbaum, Elizabeth L., Schmidt, Heather K., Fulton, Lucinda A., Cordes, Matthew G., Li, Tiandao, Ding, Li, Wilson, Richard K., Rader, Janet S., Behmaram, Behnaz, Uyar, Denise, Bradley, William, Wrangle, John, Pastore, Alessandro, Levine, Douglas A., Dao, Fanny, Gao, Jianjiong, Schultz, Nikolaus, Sander, Chris, Ladanyi, Marc, Einstein, Mark, Teeter, Randall, Benz, Stephen, Wentzensen, Nicolas, Felau, Ina, Zenklusen, Jean C., Bodelon, Clara, Demchok, John A., Yang, Liming, Sheth, Margi, Ferguson, Martin L., Tarnuzzer, Roy, Yang, Hannah, Schiffman, Mark, Zhang, Jiashan, Wang, Zhining, Davidsen, Tanja, Olaniyan, Olayinka, Hutter, Carolyn M., Sofia, Heidi J., Gordenin, Dmitry A., Chan, Kin, Roberts, Steven A., Klimczak, Leszek J., Van Waes, Carter, Chen, Zhong, Saleh, Anthony D., Cheng, Hui, Parfitt, Jeremy, Bartlett, John, Albert, Monique, Arnaout, Angel, Sekhon, Harman, Gilbert, Sebastien, Peto, Myron, Myers, Jerome, Harr, Jodi, Eckman, John, Bergsten, Julie, Tucker, Kelinda, Zach, Leigh Anne, Karlan, Beth Y., Lester, Jenny, Orsulic, Sandra, Sun, Qiang, Naresh, Rashi, Pihl, Todd, Wan, Yunhu, Zaren, Howard, Sapp, Jennifer, Miller, Judy, Drwiega, Paul, Murray, Bradley A., Zhang, Hailei, Cherniack, Andrew D., Sougnez, Carrie, Pedamallu, Chandra Sekhar, Lichtenstein, Lee, Meyerson, Matthew, Noble, Michael S., Heiman, David I., Voet, Doug, Getz, Gad, Saksena, Gordon, Kim, Jaegil, Shih, Juliann, Cho, Juok, Lawrence, Michael S., Gehlenborg, Nils, Lin, Pei, Beroukhim, Rameen, Frazer, Scott, Gabriel, Stacey B., Schumacher, Steven E., Leraas, Kristen M., Lichtenberg, Tara M., Zmuda, Erik, Bowen, Jay, Frick, Jessica, Gastier-Foster, Julie M., Wise, Lisa, Gerken, Mark, Ramirez, Nilsa C., Danilova, Ludmila, Cope, Leslie, Baylin, Stephen B., Salvesen, Helga B., Vellano, Christopher P., Ju, Zhenlin, Diao, Lixia, Zhao, Hao, Chong, Zechen, Ryan, Michael C., Martinez-Ledesma, Emmanuel, Verhaak, Roeland G., Averett Byers, Lauren, Yuan, Yuan, Chen, Ken, Ling, Shiyun, Mills, Gordon B., Lu, Yiling, Akbani, Rehan, Seth, Sahil, Liang, Han, Wang, Jing, Han, Leng, Weinstein, John N., Bristow, Christopher A., Zhang, Wei, Mahadeshwar, Harshad S., Sun, Huandong, Tang, Jiabin, Zhang, Jianhua, Song, Xingzhi, Protopopov, Alexei, Shaw, Kenna R. Mills, Chin, Lynda, Olabode, Oluwole, DiSaia, Philip, Radenbaugh, Amie, Haussler, David, Zhu, Jingchun, Stuart, Josh, Chalise, Prabhakar, Koestler, Devin, Fridley, Brooke L., Godwin, Andrew K., Madan, Rashna, Ciriello, Giovanni, Martinez, Cathleen, Higgins, Kelly, Bocklage, Therese, Auman, J. Todd, Perou, Charles M., Tan, Donghui, Parker, Joel S., Hoadley, Katherine A., Wilkerson, Matthew D., Mieczkowski, Piotr A., Skelly, Tara, Veluvolu, Umadevi, Hayes, D. Neil, Rathmell, W. Kimryn, Hoyle, Alan P., Simons, Janae V., Wu, Junyuan, Mose, Lisle E., Soloway, Matthew G., Balu, Saianand, Meng, Shaowu, Jefferys, Stuart R., Bodenheimer, Tom, Shi, Yan, Roach, Jeffrey, Thorne, Leigh B., Boice, Lori, Huang, Mei, Jones, Corbin D., Zuna, Rosemary, Walker, Joan, Gunderson, Camille, Snowbarger, Carie, Brown, David, Moxley, Katherine, Moore, Kathleen, Andrade, Kelsi, Landrum, Lisa, Mannel, Robert, McMeekin, Scott, Johnson, Starla, Nelson, Tina, Elishaev, Esther, Dhir, Rajiv, Edwards, Robert, Bhargava, Rohit, Tiezzi, Daniel G., Andrade, Jurandyr M., Noushmehr, Houtan, Gilberto Carlotti, Carlos, Jr, Tirapelli, Daniela Pretti da Cunha, Weisenberger, Daniel J., Van Den Berg, David J., Maglinte, Dennis T., Bootwalla, Moiz S., Lai, Phillip H., Triche, Timothy, Jr, Swisher, Elizabeth M., Agnew, Kathy J., Shelley, Carl Simon, Laird, Peter W., Schwarz, Julie, Grigsby, Perry, and Mutch, David

Subjects
Cervical cancer -- Genetic aspects -- Care and treatment -- Causes of, Gene mutation -- Health aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Cervical cancer remains one of the leading causes of cancer-related deaths worldwide. Here we report the extensive molecular characterization of 228 primary cervical cancers, one of the largest comprehensive genomic studies of cervical cancer to date. We observed notable APOBEC mutagenesis patterns and identified SHKBP1, ERBB3, CASP8, HLA-A and TGFBR2 as novel significantly mutated genes in cervical cancer. We also discovered amplifications in immune targets CD274 (also known as PD-L1) and PDCD1LG2 (also known as PD-L2), and the BCAR4 long non-coding RNA, which has been associated with response to lapatinib. Integration of human papilloma virus (HPV) was observed in all HPV18-related samples and 76% of HPV16-related samples, and was associated with structural aberrations and increased target-gene expression. We identified a unique set of endometrial-like cervical cancers, comprised predominantly of HPV-negative tumours with relatively high frequencies of KRAS, ARID1A and PTEN mutations. Integrative clustering of 178 samples identified keratin-low squamous, keratin-high squamous and adenocarcinoma-rich subgroups. These molecular analyses reveal new potential therapeutic targets for cervical cancers., Author(s): The Cancer Genome Atlas Research Network; Albert Einstein College of Medicine; Robert D. Burk [1]; Zigui Chen [1]; Analytical Biological Services; Charles Saller [2]; Katherine Tarvin [2]; Barretos Cancer [...]

Published
2017
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11. Integrated genomic characterization of oesophageal carcinoma

Author

Kim, Jihun, Bowlby, Reanne, Mungall, Andrew J., Robertson, Gordon A., Odze, Robert D., Cherniack, Andrew D., Shih, Juliann, Pedamallu, Chandra Sekhar, Cibulskis, Carrie, Dunford, Andrew, Meier, Samuel R., Kim, Jaegil, Raphael, Benjamin J., Wu, Hsin-Ta, Wong, Alexandra M., Willis, Joseph E., Bass, Adam J., Derks, Sarah, Garman, Katherine, McCall, Shannon J., Wiznerowicz, Maciej, Pantazi, Angeliki, Parfenov, Michael, Thorsson, Vésteinn, Shmulevich, Ilya, Dhankani, Varsha, Miller, Michael, Sakai, Ryo, Wang, Kenneth, Schultz, Nikolaus, Shen, Ronglai, Arora, Arshi, Weinhold, Nils, Sánchez-Vega, Francisco, Kelsen, David P., Zhang, Julia, Felau, Ina, Demchok, John, Rabkin, Charles S., Camargo, Constanza M., Zenklusen, Jean Claude, Bowen, Jay, Leraas, Kristen, Lichtenberg, Tara M., Curtis, Christina, Seoane, Jose A., Ojesina, Akinyemi I., Beer, David G., Gulley, Margaret L., Pennathur, Arjun, Luketich, James D., Zhou, Zhongren, Weisenberger, Daniel J., Akbani, Rehan, Lee, Ju-Seog, Liu, Wenbin, Mills, Gordon B., Zhang, Wei, Reid, Brian J, Hinoue, Toshinori, Laird, Peter W., Shen, Hui, Piazuelo, Blanca M., Schneider, Barbara G., McLellan, Michael, Taylor-Weiner, Amaro, Cibulskis, Carrie, Lawrence, Michael, Cibulskis, Kristian, Stewart, Chip, Getz, Gad, Lander, Eric, Gabriel, Stacey B., Ding, Li, McLellan, Michael D., Miller, Christopher A., Appelbaum, Elizabeth L., Cordes, Matthew G., Fronick, Catrina C., Fulton, Lucinda A., Mardis, Elaine R., Wilson, Richard K., Schmidt, Heather K., Fulton, Robert S., Ally, Adrian, Balasundaram, Miruna, Bowlby, Reanne, Carlsen, Rebecca, Chuah, Eric, Dhalla, Noreen, Holt, Robert A., Jones, Steven J. M., Kasaian, Katayoon, Brooks, Denise, Li, Haiyan I., Ma, Yussanne, Marra, Marco A., Mayo, Michael, Moore, Richard A., Mungall, Andrew J., Mungall, Karen L., Robertson, Gordon A., Schein, Jacqueline E., Sipahimalani, Payal, Tam, Angela, Thiessen, Nina, Wong, Tina, Cherniack, Andrew D., Shih, Juliann, Pedamallu, Chandra Sekhar, Beroukhim, Rameen, Bullman, Susan, Cibulskis, Carrie, Murray, Bradley A., Saksena, Gordon, Schumacher, Steven E., Gabriel, Stacey, Meyerson, Matthew, Hadjipanayis, Angela, Kucherlapati, Raju, Pantazi, Angeliki, Parfenov, Michael, Ren, Xiaojia, Park, Peter J., Lee, Semin, Kucherlapati, Melanie, Yang, Lixing, Baylin, Stephen B., Hoadley, Katherine A., Weisenberger, Daniel J., Bootwalla, Moiz S., Lai, Phillip H., Van Den Berg, David J., Berrios, Mario, Holbrook, Andrea, Akbani, Rehan, Hwang, Jun-Eul, Jang, Hee-Jin, Liu, Wenbin, Weinstein, John N., Lee, Ju-Seog, Lu, Yiling, Sohn, Bo Hwa, Mills, Gordon, Seth, Sahil, Protopopov, Alexei, Bristow, Christopher A., Mahadeshwar, Harshad S., Tang, Jiabin, Song, Xingzhi, Zhang, Jianhua, Laird, Peter W., Hinoue, Toshinori, Shen, Hui, Cho, Juok, Defrietas, Timothy, Frazer, Scott, Gehlenborg, Nils, Heiman, David I., Lawrence, Michael S., Lin, Pei, Meier, Samuel R., Noble, Michael S., Voet, Doug, Zhang, Hailei, Kim, Jaegil, Polak, Paz, Saksena, Gordon, Chin, Lynda, Getz, Gad, Wong, Alexandra M., Raphael, Benjamin J., Wu, Hsin-Ta, Lee, Semin, Park, Peter J., Yang, Lixing, Thorsson, Vésteinn, Bernard, Brady, Iype, Lisa, Miller, Michael, Reynolds, Sheila M., Shmulevich, Ilya, Dhankani, Varsha, Abeshouse, Adam, Arora, Arshi, Armenia, Joshua, Kundra, Ritika, Ladanyi, Marc, Lehmann, Kjong-Van, Gao, Jianjiong, Sander, Chris, Schultz, Nikolaus, Sánchez-Vega, Francisco, Shen, Ronglai, Weinhold, Nils, Chakravarty, Debyani, Zhang, Hongxin, Radenbaugh, Amie, Hegde, Apruva, Akbani, Rehan, Liu, Wenbin, Weinstein, John N., Chin, Lynda, Bristow, Christopher A., Lu, Yiling, Penny, Robert, Crain, Daniel, Gardner, Johanna, Curley, Erin, Mallery, David, Morris, Scott, Paulauskis, Joseph, Shelton, Troy, Shelton, Candace, Bowen, Jay, Frick, Jessica, Gastier-Foster, Julie M., Gerken, Mark, Leraas, Kristen M., Lichtenberg, Tara M., Ramirez, Nilsa C., Wise, Lisa, Zmuda, Erik, Tarvin, Katherine, Saller, Charles, Park, Young Soo, Button, Michael, Carvalho, Andre L., Reis, Rui Manuel, Matsushita, Marcus Medeiros, Lucchesi, Fabiano, de Oliveira, Antonio Talvane, Le, Xuan, Paklina, Oxana, Setdikova, Galiya, Lee, Jae-Hyuck, Bennett, Joseph, Iacocca, Mary, Huelsenbeck-Dill, Lori, Potapova, Olga, Voronina, Olga, Liu, Ouida, Fulidou, Victoria, Cates, Crystal, Sharp, Alexis, Behera, Madhusmitara, Force, Seth, Khuri, Fadio, Owonikoko, Taofeek, Pickens, Allan, Ramalingam, Suresh, Sica, Gabriel, Dinjens, Winand, van Nistelrooij, Anna, Wijnhoven, Bas, Sandusky, George, Stepa, Serghei, Crain, Daniel, Paulauskis, Joseph, Penny, Robert, Gardner, Johanna, Mallery, David, Morris, Scott, Shelton, Troy, Shelton, Candace, Curley, Erin, Juhl, Hartmut, Zornig, Carsten, Kwon, Sun Young, Kelsen, David, Kim, Hark Kyun, Bartlett, John, Parfitt, Jeremy, Chetty, Runjan, Darling, Gail, Knox, Jennifer, Wong, Rebecca, El-Zimaity, Haila, Liu, Geoffrey, Boussioutas, Alex, Park, Do Young, Kemp, Rafael, Carlotti, Carlos Gilberto, da Cunha Tirapelli, Daniela Pretti, Saggioro, Fabiano Pinto, Sankarankutty, Ajith Kumar, Noushmehr, Houtan, dos Santos, Jose Sebastião, Trevisan, Felipe Amstalden, Eschbacher, Jennifer, Dubina, Michael, Mozgovoy, Eugene, Carey, Frank, Chalmers, Sally, Forgie, Ian, Godwin, Andrew, Reilly, Colleen, Madan, Rashna, Naima, Zaid, Ferrer-Torres, Daysha, Vinco, Michele, Rathmell, Kimryn W., Dhir, Rajiv, Luketich, James, Pennathur, Arjun, Ajani, Jaffer A., McCall, Shannon J., Janjigian, Yelena, Kelsen, David, Ladanyi, Marc, Tang, Laura, Camargo, Constanza M., Ajani, Jaffer A., Cheong, Jae-Ho, Chudamani, Sudha, Liu, Jai, Lolla, Laxmi, Naresh, Rashi, Pihl, Todd, Sun, Qiang, Wan, Yunhu, Wu, Ye, Demchok, John A., Felau, Ina, Ferguson, Martin L., Shaw, Kenna R. Mills, Sheth, Margi, Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Zenklusen, Jean Claude, Hutter, Carolyn M., Sofia, Heidi J., and Zhang, Jiashan

Published
2017
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12. Cell-of-origin chromatin organization shapes the mutational landscape of cancer

Author

Polak, Paz, Karlic, Rosa, Koren, Amnon, Thurman, Robert, Sandstrom, Richard, Lawrence, Michael S., Reynolds, Alex, Rynes, Eric, Vlahovicek, Kristian, Stamatoyannopoulos, John A., and Sunyaev, Shamil R.

Subjects
Gene mutations -- Research, Chromatin -- Health aspects, Genetic research, Cancer -- Genetic aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Cancer is a disease potentiated by mutations in somatic cells. Cancer mutations are not distributed uniformly along the human genome. Instead, different human genomic regions vary by up to fivefold in the local density of cancer somatic mutations (1), posing a fundamental problem for statistical methods used in cancer genomics. Epigenomic organization has been proposed as a major determinant of the cancer mutational landscape (1-5). However, both somatic mutagenesis and epigenomic features are highly cell-type-specific (6,7). We investigated the distribution of mutations in multiple independent samples of diverse cancer types and compared them to cell-type-specific epigenomic features. Here we show that chromatin accessibility and modification, together with replication timing, explain up to 86% of the variance in mutation rates along cancer genomes. The best predictors of local somatic mutation density are epigenomic features derived from the most likely cell type of origin of the corresponding malignancy. Moreover, we find that cell-of-origin chromatin features are much stronger determinants of cancer mutation profiles than chromatin features of matched cancer cell lines. Furthermore, we show that the cell type of origin of a cancer can be accurately determined based on the distribution of mutations along its genome. Thus, the DNA sequence of a cancer genome encompasses a wealth of information about the identity and epigenomic features of its cell of origin., Recent studies have begun to address the underlying causes of cancer mutational heterogeneity by comparing mutation rate variation to the distribution of sequence features, gene expression and epigenetic marks along [...]

Published
2015

13. Discovery and saturation analysis of cancer genes across 21 tumour types

Author

Lawrence, Michael S., Stojanov, Petar, Mermel, Craig H., Robinson, James T., Garraway, Levi A., Golub, Todd R., Meyerson, Matthew, Gabriel, Stacey B., Lander, Eric S., and Getz, Gad

Subjects
Oncology, Experimental, Tumors -- Physiological aspects -- Genetic aspects, Cancer -- Genetic aspects -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Although a few cancer genes are mutated in a high proportion of tumours of a given type (>20%), most are mutated at intermediate frequencies (2-20%). To explore the feasibility of creating a comprehensive catalogue of cancer genes, we analysed somatic point mutations in exome sequences from 4,742 human cancers and their matched normal-tissue samples across 21 cancer types. We found that large-scale genomic analysis can identify nearly all known cancer genes in these tumour types. Our analysis also identified 33 genes that were not previously known to be significantly mutated in cancer, including genes related to proliferation, apoptosis, genome stability, chromatin regulation, immune evasion, RNA processing and protein homeostasis. Down-sampling analysis indicates that larger sample sizes will reveal many more genes mutated at clinically important frequencies. We estimate that near-saturation may be achieved with 600-5,000 samples per tumour type, depending on background mutation frequency. The results may help to guide the next stage of cancer genomics., Comprehensive knowledge of the genes underlying human cancers is a critical foundation for cancer diagnostics, therapeutics, clinical-trial design and selection of rational combination therapies. It is now possible to use [...]

Published
2014
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14. How insulin engages its primary binding site on the insulin receptor

Author

Menting, John G., Whittaker, Jonathan, Margetts, Mai B., Whittaker, Linda J., Kong, Geoffrey K.-W., Smith, Brian J., Watson, Christopher J., Zakova, Lenka, Kletvikova, Emilia, Jiracek, Jiri, Chan, Shu Jin, Steiner, Donald F., Dodson, Guy G., Brzozowski, Andrzej M., Weiss, Michael A., Ward, Colin W., and Lawrence, Michael C.

Subjects
Insulin -- Receptors -- Physiological aspects -- Genetic aspects -- Research, Protein binding -- Physiological aspects -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Insulin receptor signalling has a central role in mammalian biology, regulating cellular metabolism, growth, division, differentiation and survival (1,2). Insulin resistance contributes to the pathogenesis of type 2 diabetes mellitus [...]

Published
2013

15. Sequence analysis of mutations and translocations across breast cancer subtypes

Author

Banerji, Shantanu, Cibulskis, Kristian, Rangel-Escareno, Claudia, Brown, Kristin K., Carter, Scott L., Frederick, Abbie M., Lawrence, Michael S., Sivachenko, Andrey Y., Sougnez, Carrie, Zou, Lihua, Cortes, Maria L., Fernandez-Lopez, Juan C., Peng, Shouyong, Ardlie, Kristin G., Auclair, Daniel, Bautista-Pina, Veronica, Duke, Fujiko, Francis, Joshua, Jung, Joonil, Maffuz-Aziz, Antonio, Onofrio, Robert C., Parkin, Melissa, Pho, Nam H., Quintanar-Jurado, Valeria, Ramos, Alex H., Rebollar-Vega, Rosa, Rodriguez-Cuevas, Sergio, Romero-Cordoba, Sandra L., Schumacher, Steven E., Stransky, Nicolas, Thompson, Kristin M., Uribe-Figueroa, Laura, Baselga, Jose, Beroukhim, Rameen, Polyak, Kornelia, Sgroi, Dennis C., Richardson, Andrea L., Jimenez-Sanchez, Gerardo, Lander, Eric S., Gabriel, Stacey B., Garraway, Levi A., Golub, Todd R., Melendez-Zajgla, Jorge, Toker, Alex, Getz, Gad, Hidalgo-Miranda, Alfredo, and Meyerson, Matthew

Subjects
Gene mutations -- Research, Exome sequencing -- Research, Translocation (Genetics) -- Research, Cancer -- Genetic aspects, Breast cancer -- Genetic aspects -- Analysis -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Shantanu Banerji [1, 2, 3, 15, 16]; Kristian Cibulskis [1, 16]; Claudia Rangel-Escareno [4, 16]; Kristin K. Brown [5, 16]; Scott L. Carter [1]; Abbie M. Frederick [1]; Michael [...]

Published
2012
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16. Huge whole-genome study of human metastatic cancers

Author

Wise, Jillian F. and Lawrence, Michael S.

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

A better understanding of the genetic changes that enable cancers to spread is crucial. A comprehensive study of whole-genome sequences from metastatic cancer will help researchers to achieve this goal. Comprehensive analysis of genetic changes across metastatic cancers., Author(s): Jillian F. Wise, Michael S. Lawrence Author Affiliations: Huge whole-genome study of human metastatic cancers The major cause of cancer-related deaths is the spread of cancer cells from their [...]

Published
2019
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17. Comprehensive molecular characterization of urothelial bladder carcinoma

Author

Weinstein, John N., Akbani, Rehan, Broom, Bradley M., Wang, Wenyi, Verhaak, Roeland G. W., McConkey, David, Lerner, Seth, Morgan, Margaret, Creighton, Chad J., Smith, Carolyn, Kwiatkowski, David J., Cherniack, Andrew D., Kim, Jaegil, Pedamallu, Chandra Sekhar, Noble, Michael S., Al-Ahmadie, Hikmat A., Reuter, Victor E., Rosenberg, Jonathan E., Bajorin, Dean F., Bochner, Bernard H., Solit, David B., Koppie, Theresa, Robinson, Brian, Gordenin, Dmitry A., Fargo, David, Klimczak, Leszek J., Roberts, Steven A., Au, Jessie, Laird, Peter W., Hinoue, Toshinori, Schultz, Nikolaus, Ramirez, Ricardo, Hansel, Donna, Hoadley, Katherine A., Kim, William Y., Damrauer, Jeffrey S., Baylin, Stephen B., Mungall, Andrew J., Robertson, Gordon A., Chu., Andy, Sougnez, Carrie, Cibulskis, Kristian, Lichtenstein, Lee, Sivachenko, Andrey, Stewart, Chip, Lawrence, Michael S., Getz, Gad, Lander, Eric, Gabriel., Stacey B., Donehower, Lawrence, Carter, Scott L., Saksena, Gordon, Schumacher, Steven E., Freeman, Samuel S., Jung, Joonil, Bhatt, Ami S., Pugh, Trevor, Beroukhim, Rameen, Gabriel, Stacey B., Meyerson, Matthew, Chu, Andy, Ally, Adrian, Balasundaram, Miruna, Butterfield, Yaron S. N., Dhalla, Noreen, Hirst, Carrie, Holt, Robert A., Jones, Steven J. M., Lee, Darlene, Li, Haiyan I., Marra, Marco A., Mayo, Michael, Moore, Richard A., Schein, Jacqueline E., Sipahimalani, Payal, Tam, Angela, Thiessen, Nina, Wong, Tina, Wye, Natasja, Bowlby, Reanne, Chuah, Eric, Guin, Ranabir, Shen, Hui, Bootwalla, Moiz S., Jr, Timothy Triche, Lai, Phillip H., Van Den Berg, David J., Weisenberger, Daniel J., Balu, Saianand, Bodenheimer, Tom, Damrauer Alan P. Hoyle, Jeffrey S., Jefferys, Stuart R., Meng, Shaowu, Mose, Lisle E., Simons, Janae V., Soloway, Mathew G., Wu, Junyuan, Parker, Joel S., Hayes, Neil D., Roach, Jeffrey, Buda, Elizabeth, Jones, Corbin D., Mieczkowski, Piotr A., Tan, Donghui, Veluvolu, Umadevi, Waring, Scot, Auman, Todd J., Perou, Charles M., Wilkerson, Matthew D., Santoso, Netty, Parfenov, Michael, Ren, Xiaojia, Pantazi, Angeliki, Hadjipanayis, Angela, Seidman, Jonathan, Kucherlapati, Raju, Lee, Semin, Yang, Lixing, Park, Peter J., Xu, Andrew Wei, Protopopov, Alexei, Zhang, Jianhua, Bristow, Christopher, Mahadeshwar, Harshad S., Seth, Sahil, Song, Xingzhi, Tang, Jiabin, Zeng, Dong, Chin, Lynda, Guo, Charles, Casasent, Tod D., Liu, Wenbin, Ju, Zhenlin, Motter, Thomas, Peng, Bo, Ryan, Michael, Su, Xiaoping, Yang, Ji-Yeon, Lorenzi, Philip L., Yao, Hui, Zhang, Nianxiang, Zhang, Jiexin, Mills, Gordon B., Cho, Juok, DiCara, Daniel, Frazer, Scott, Gehlenborg, Nils, Heiman, David I., Lin, Pei, Liu, Yingchun, Stojanov, Petar, Voet, Doug, Zhang, Hailei, Zou, Lihua, Bernard, Brady, Kreisberg, Dick, Reynolds, Sheila, Rovira, Hector, Shmulevich, Ilya, Gao, Jianjiong, Jacobsen, Anders, Aksoy, Arman B., Antipin, Yevgeniy, Ciriello, Giovanni, Dresdner, Gideon, Gross, Benjamin, Lee, William, Reva, Boris, Shen, Ronglai, Sinha, Rileen, Sumer, Onur S., Weinhold, Nils, Ladanyi, Marc, Sander, Chris, Benz, Christopher, Carlin, Daniel, Haussler, David, Ng, Sam, Paull, Evan O., Stuart, Joshua, Zhu, Jing, Liu, Yuexin, Zhang, Wei, Taylor, Barry S., Lichtenberg, Tara M., Zmuda, Erik, Barr, Thomas, Black, Aaron D., George, Myra, Hanf, Benjamin, Helsel, Carmen, McAllister, Cynthia, Ramirez, Nilsa C., Tabler, Teresa R., Weaver, Stephanie, Wise, Lisa, Bowen, Jay, Gastier-Foster, Julie M., Jian, Weiguo, Tello, Sebrina, Ittman, Michael, Castro, Patricia, McClenden, Whitney D., Gibbs, Richard, Saller, Charles, Tarvin, Katherine, DiPiero, Jennifer M., Owens, Jennifer, Bollag, Roni, Li, Qiang, Weinberger, Paul, Czerwinski, Christine, Huelsenbeck-Dill, Lori, Iacocca, Mary, Petrelli, Nicholas, Rabeno, Brenda, Swanson, Pat, Shelton, Troy, Curley, Erin, Gardner, Johanna, Mallery, David, Penny, Robert, Van Bang, Nguyen, Thi Hanh, Phan, Kohl, Bernard, Van Le, Xuan, Duc Phu, Bui, Thorp, Richard, Tien, Nguyen Viet, Vinh, Le Quang, Sandusky, George, Burks, Eric, Christ, Kimberly, Gee, Jason, Holway, Antonia, Moinzadeh, Alireza, Sorcini, Andrea, Sullivan, Travis, Garcia-Grossman, Ilana R., Regazzi, Ashley M., Boice, Lori, Rathmell, Wendy Kimryn, Thorne, Leigh, Bastacky, Sheldon, Davies, Benjamin, Dhir, Rajiv, Gingrich, Jeffrey, Hrebinko, Ronald, Maranchie, Jodi, Nelson, Joel, Parwani, Anil, Bshara, Wiam, Gaudioso, Carmelo, Morrison, Carl, Alexopoulou, Vina, Bartlett, John, Engel, Jay, Kodeeswaran, Sugy, Antic, Tatjana, O’Donnell, Peter H., Smith, Norm D., Steinberg, Gary D., Egea, Sophie, Gomez-Fernandez, Carmen, Herbert, Lynn, Jorda, Merce, Soloway, Mark, Beaver, Allison, Carter, Suzie, Kapur, Payal, Lewis, Cheryl, Lotan, Yair, Bondaruk, Jolanta, Czerniak, Bogdan, Skinner, Eila, Aldape, Kenneth, Jensen, Mark A., Kahn, Ari B., Pihl, Todd D., Pot, David A., Srinivasan, Deepak, Wan, Yunhu, Ferguson, Martin L., Zenklusen, Jean Claude, Davidsen, Tanja, Demchok, John A., Mills Shaw, Kenna R., Sheth, Margi, Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Hutter, Carolyn, Ozenberger, Bradley A., Sofia, Heidi J., and Eley, Greg

Published
2014
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18. Landscape of genomic alterations in cervical carcinomas

Author

Ojesina, Akinyemi I., Lichtenstein, Lee, Freeman, Samuel S., Pedamallu, Chandra Sekhar, Imaz-Rosshandler, Ivan, Pugh, Trevor J., Cherniack, Andrew D., Ambrogio, Lauren, Cibulskis, Kristian, Bertelsen, Bjørn, Romero-Cordoba, Sandra, Treviño, Victor, Vazquez-Santillan, Karla, Guadarrama, Alberto Salido, Wright, Alexi A., Rosenberg, Mara W., Duke, Fujiko, Kaplan, Bethany, Wang, Rui, Nickerson, Elizabeth, Walline, Heather M., Lawrence, Michael S., Stewart, Chip, Carter, Scott L., McKenna, Aaron, Rodriguez-Sanchez, Iram P., Espinosa-Castilla, Magali, Woie, Kathrine, Bjorge, Line, Wik, Elisabeth, Halle, Mari K., Hoivik, Erling A., Krakstad, Camilla, Gabiño, Nayeli Belem, Gómez-Macías, Gabriela Sofia, Valdez-Chapa, Lezmes D., Garza-Rodríguez, María Lourdes, Maytorena, German, Vazquez, Jorge, Rodea, Carlos, Cravioto, Adrian, Cortes, Maria L., Greulich, Heidi, Crum, Christopher P., Neuberg, Donna S., Hidalgo-Miranda, Alfredo, Escareno, Claudia Rangel, Akslen, Lars A., Carey, Thomas E., Vintermyr, Olav K., Gabriel, Stacey B., Barrera-Saldaña, Hugo A., Melendez-Zajgla, Jorge, Getz, Gad, Salvesen, Helga B., and Meyerson, Matthew

Published
2014
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19. Somatic mutations affect key pathways in lung adenocarcinoma

Author

Ding, Li, Getz, Gad, Wheeler, David A., Mardis, Elaine R., McLellan, Michael D., Cibulskis, Kristian, Sougnez, Carrie, Greulich, Heidi, Muzny, Donna M., Morgan, Margaret B., Fulton, Lucinda, Fulton, Robert S., Zhang, Qunyuan, Wendl, Michael C., Lawrence, Michael S., Larson, David E., Chen, Ken, Dooling, David J., Sabo, Aniko, Hawes, Alicia C., Shen, Hua, Jhangiani, Shalini N., Lewis, Lora R., Hall, Otis, Zhu, Yiming, Mathew, Tittu, Ren, Yanru, Yao, Jiqiang, Scherer, Steven E., Clerc, Kerstin, Metcalf, Ginger A., Ng, Brian, Milosavljevic, Aleksandar, Gonzalez-Garay, Manuel L., Osborne, John R., Meyer, Rick, Shi, Xiaoqi, Tang, Yuzhu, Koboldt, Daniel C., Lin, Ling, Abbott, Rachel, Miner, Tracie L., Pohl, Craig, Fewell, Ginger, Haipek, Carrie, Schmidt, Heather, Dunford-Shore, Brian H., Kraja, Aldi, Crosby, Seth D., Sawyer, Christopher S., Vickery, Tammi, Sander, Sacha, Robinson, Jody, Winckler, Wendy, Baldwin, Jennifer, Chirieac, Lucian R., Dutt, Amit, Fennell, Tim, Hanna, Megan, Johnson, Bruce E., Onofrio, Robert C., Thomas, Roman K., Tonon, Giovanni, Weir, Barbara A., Zhao, Xiaojun, Ziaugra, Liuda, Zody, Michael C., Giordano, Thomas, Orringer, Mark B., Roth, Jack A., Spitz, Margaret R., Wistuba, Ignacio I., Ozenberger, Bradley, Good, Peter J., Chang, Andrew C., Beer, David G., Watson, Mark A., Ladanyi, Marc, Broderick, Stephen, Yoshizawa, Akihiko, Travis, William D., Pao, William, Province, Michael A., Weinstock, George M., Varmus, Harold E., Gabriel, Stacey B., Lander, Eric S., Gibbs, Richard A., Meyerson, Matthew, and Wilson, Richard K.

Subjects
Gene mutations -- Research -- Physiological aspects -- Genetic aspects, Nucleotide sequencing -- Research -- Physiological aspects -- Genetic aspects, Adenocarcinoma -- Genetic aspects -- Research -- Care and treatment -- Prognosis -- Diagnosis, DNA sequencing -- Research -- Physiological aspects -- Genetic aspects, Lung cancer -- Genetic aspects -- Research -- Care and treatment -- Diagnosis -- Prognosis, Environmental issues, Science and technology, Zoology and wildlife conservation, Diagnosis, Care and treatment, Physiological aspects, Genetic aspects, Research, Prognosis
Abstract

Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well-classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations [...]

Published
2008

20. Recurrent and functional regulatory mutations in breast cancer

Author

Rheinbay, Esther, Parasuraman, Prasanna, Grimsby, Jonna, Tiao, Grace, Engreitz, Jesse M., Kim, Jaegil, Lawrence, Michael S., Taylor-Weiner, Amaro, Rodriguez-Cuevas, Sergio, Rosenberg, Mara, Hess, Julian, Stewart, Chip, Maruvka, Yosef E., Stojanov, Petar, Cortes, Maria L., Seepo, Sara, Cibulskis, Carrie, Tracy, Adam, Pugh, Trevor J., Lee, Jesse, Zheng, Zongli, Ellisen, Leif W., Iafrate, A. John, Boehm, Jesse S., Gabriel, Stacey B., Meyerson, Matthew, Golub, Todd R., Baselga, Jose, Hidalgo-Miranda, Alfredo, Shioda, Toshi, Bernards, Andre, Lander, Eric S., and Getz, Gad

Subjects
Cancer genetics -- Genetic aspects -- Analysis -- Health aspects -- Research, Cancer research, Tumors -- Genetic aspects, Breast cancer -- Genetic aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Genomic analysis of tumours has led to the identification of hundreds of cancer genes on the basis of the presence of mutations in protein-coding regions. By contrast, much less is known about cancer-causing mutations in non-coding regions. Here we perform deep sequencing in 360 primary breast cancers and develop computational methods to identify significantly mutated promoters. Clear signals are found in the promoters of three genes. FOXA1, a known driver of hormone-receptor positive breast cancer, harbours a mutational hotspot in its promoter leading to overexpression through increased E2F binding. RMRP and NEAT1, two non-coding RNA genes, carry mutations that affect protein binding to their promoters and alter expression levels. Our study shows that promoter regions harbour recurrent mutations in cancer with functional consequences and that the mutations occur at similar frequencies as in coding regions. Power analyses indicate that more such regions remain to be discovered through deep sequencing of adequately sized cohorts of patients., Author(s): Esther Rheinbay [1, 2]; Prasanna Parasuraman [2]; Jonna Grimsby [1]; Grace Tiao [1]; Jesse M. Engreitz [1, 3]; Jaegil Kim [1]; Michael S. Lawrence [1, 2]; Amaro Taylor-Weiner [1]; [...]

Published
2017
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21. Mutational heterogeneity in cancer and the search for new cancer-associated genes

Author

Lawrence, Michael S., Stojanov, Petar, Polak, Paz, Kryukov, Gregory V., Cibulskis, Kristian, Sivachenko, Andrey, Carter, Scott L., Stewart, Chip, Mermel, Craig H., Roberts, Steven A., Kiezun, Adam, Hammerman, Peter S., McKenna, Aaron, Drier, Yotam, Zou, Lihua, Ramos, Alex H., Pugh, Trevor J., Stransky, Nicolas, Helman, Elena, Kim, Jaegil, Sougnez, Carrie, Ambrogio, Lauren, Nickerson, Elizabeth, Shefler, Erica, Cortés, Maria L., Auclair, Daniel, Saksena, Gordon, Voet, Douglas, Noble, Michael, DiCara, Daniel, Lin, Pei, Lichtenstein, Lee, Heiman, David I., Fennell, Timothy, Imielinski, Marcin, Hernandez, Bryan, Hodis, Eran, Baca, Sylvan, Dulak, Austin M., Lohr, Jens, Landau, Dan-Avi, Wu, Catherine J., Melendez-Zajgla, Jorge, Hidalgo-Miranda, Alfredo, Koren, Amnon, McCarroll, Steven A., Mora, Jaume, Lee, Ryan S., Crompton, Brian, Onofrio, Robert, Parkin, Melissa, Winckler, Wendy, Ardlie, Kristin, Gabriel, Stacey B., Roberts, Charles W. M., Biegel, Jaclyn A., Stegmaier, Kimberly, Bass, Adam J., Garraway, Levi A., Meyerson, Matthew, Golub, Todd R., Gordenin, Dmitry A., Sunyaev, Shamil, Lander, Eric S., and Getz, Gad

Published
2013
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22. Comprehensive molecular characterization of clear cell renal cell carcinoma

Author

Creighton, Chad J., Morgan, Margaret, Gunaratne, Preethi H., Wheeler, David A., Gibbs, Richard A., Robertson, Gordon A., Chu, Andy, Beroukhim, Rameen, Cibulskis, Kristian, Signoretti, Sabina, Hsin-Ta Wu, Fabio Vandin, Raphael, Benjamin J., Verhaak, Roel G. W., Tamboli, Pheroze, Torres-Garcia, Wandaliz, Akbani, Rehan, Weinstein, John N., Reuter, Victor, Hsieh, James J., Brannon, Rose A., Ari Hakimi, A., Jacobsen, Anders, Ciriello, Giovanni, Reva, Boris, Ricketts, Christopher J., Linehan, Marston W., Stuart, Joshua M., Rathmell, Kimryn W., Shen, Hui, Laird, Peter W., Muzny, Donna, Davis, Caleb, Xi, Liu, Chang, Kyle, Kakkar, Nipun, Treviño, Lisa R., Benton, Susan, Reid, Jeffrey G., Morton, Donna, Doddapaneni, Harsha, Han, Yi, Lewis, Lora, Dinh, Huyen, Kovar, Christie, Zhu, Yiming, Santibanez, Jireh, Wang, Min, Hale, Walker, Kalra, Divya, Getz, Gad, Lawrence, Michael S., Sougnez, Carrie, Carter, Scott L., Sivachenko, Andrey, Lichtenstein, Lee, Stewart, Chip, Voet, Doug, Fisher, Sheila, Gabriel, Stacey B., Lander, Eric, Schumacher, Steve E., Tabak, Barbara, Saksena, Gordon, Onofrio, Robert C., Cherniack, Andrew D., Gentry, Jeff, Ardlie, Kristin, Meyerson, Matthew, Chun, Hye-Jung E., Mungall, Andrew J., Sipahimalani, Payal, Stoll, Dominik, Ally, Adrian, Balasundaram, Miruna, Butterfield, Yaron S. N., Carlsen, Rebecca, Carter, Candace, Chuah, Eric, Coope, Robin J. N., Dhalla, Noreen, Gorski, Sharon, Guin, Ranabir, Hirst, Carrie, Hirst, Martin, Holt, Robert A., Lebovitz, Chandra, Lee, Darlene, Li, Haiyan I., Mayo, Michael, Moore, Richard A., Pleasance, Erin, Plettner, Patrick, Schein, Jacqueline E., Shafiei, Arash, Slobodan, Jared R., Tam, Angela, Thiessen, Nina, Varhol, Richard J., Wye, Natasja, Zhao, Yongjun, Birol, Inanc, Jones, Steven J. M., Marra, Marco A., Auman, Todd J., Tan, Donghui, Jones, Corbin D., Hoadley, Katherine A., Mieczkowski, Piotr A., Mose, Lisle E., Jefferys, Stuart R., Topal, Michael D., Liquori, Christina, Turman, Yidi J., Shi, Yan, Waring, Scot, Buda, Elizabeth, Walsh, Jesse, Wu, Junyuan, Bodenheimer, Tom, Hoyle, Alan P., Simons, Janae V., Soloway, Mathew G., Balu, Saianand, Parker, Joel S., Hayes, Neil D., Perou, Charles M., Kucherlapati, Raju, Park, Peter, Triche, Timothy, Jr, Weisenberger, Daniel J., Lai, Phillip H., Bootwalla, Moiz S., Maglinte, Dennis T., Mahurkar, Swapna, Berman, Benjamin P., Van Den Berg, David J., Cope, Leslie, Baylin, Stephen B., Noble, Michael S., DiCara, Daniel, Zhang, Hailei, Cho, Juok, Heiman, David I., Gehlenborg, Nils, Mallard, William, Lin, Pei, Frazer, Scott, Stojanov, Petar, Liu, Yingchun, Zhou, Lihua, Kim, Jaegil, Chin, Lynda, Vandin, Fabio, Wu, Hsin-Ta, Benz, Christopher, Yau, Christina, Reynolds, Sheila M., Shmulevich, Ilya, Verhaak, Roel G.W., Vegesna, Rahul, Kim, Hoon, Zhang, Wei, Cogdell, David, Jonasch, Eric, Ding, Zhiyong, Lu, Yiling, Zhang, Nianxiang, Unruh, Anna K., Casasent, Tod D., Wakefield, Chris, Tsavachidou, Dimitra, Mills, Gordon B., Schultz, Nikolaus, Antipin, Yevgeniy, Gao, Jianjiong, Cerami, Ethan, Gross, Benjamin, Aksoy, Arman B., Sinha, Rileen, Weinhold, Nils, Sumer, Onur S., Taylor, Barry S., Shen, Ronglai, Ostrovnaya, Irina, Berger, Michael F., Ladanyi, Marc, Sander, Chris, Fei, Suzanne S., Stout, Andrew, Spellman, Paul T., Rubin, Daniel L., Liu, Tiffany T., Ng, Sam, Paull, Evan O., Carlin, Daniel, Goldstein, Theodore, Waltman, Peter, Ellrott, Kyle, Zhu, Jing, Haussler, David, Xiao, Weimin, Shelton, Candace, Gardner, Johanna, Penny, Robert, Sherman, Mark, Mallery, David, Morris, Scott, Paulauskis, Joseph, Burnett, Ken, Shelton, Troy, Kaelin, William G., Choueiri, Toni, Atkins, Michael B., Curley, Erin, Tickoo, Satish, Thorne, Leigh, Boice, Lori, Huang, Mei, Fisher, Jennifer C., Vocke, Cathy D., Peterson, James, Worrell, Robert, Merino, Maria J., Schmidt, Laura S., Czerniak, Bogdan A., Aldape, Kenneth D., Wood, Christopher G., Boyd, Jeff, Weaver, JoEllen, Iacocca, Mary V., Petrelli, Nicholas, Witkin, Gary, Brown, Jennifer, Czerwinski, Christine, Huelsenbeck-Dill, Lori, Rabeno, Brenda, Myers, Jerome, Morrison, Carl, Bergsten, Julie, Eckman, John, Harr, Jodi, Smith, Christine, Tucker, Kelinda, Zach, Leigh Anne, Bshara, Wiam, Gaudioso, Carmelo, Dhir, Rajiv, Maranchie, Jodi, Nelson, Joel, Parwani, Anil, Potapova, Olga, Fedosenko, Konstantin, Cheville, John C., Thompson, Houston R., Mosquera, Juan M., Rubin, Mark A., Blute, Michael L., Pihl, Todd, Jensen, Mark, Sfeir, Robert, Kahn, Ari, Chu, Anna, Kothiyal, Prachi, Snyder, Eric, Pontius, Joan, Ayala, Brenda, Backus, Mark, Walton, Jessica, Baboud, Julien, Berton, Dominique, Nicholls, Matthew, Srinivasan, Deepak, Raman, Rohini, Girshik, Stanley, Kigonya, Peter, Alonso, Shelley, Sanbhadti, Rashmi, Barletta, Sean, Pot, David, Sheth, Margi, Demchok, John A., Davidsen, Tanja, Wang, Zhining, Yang, Liming, Tarnuzzer, Roy W., Zhang, Jiashan, Eley, Greg, Ferguson, Martin L., Mills Shaw, Kenna R., Guyer, Mark S., Ozenberger, Bradley A., and Sofia, Heidi J.

Published
2013
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23. Comprehensive molecular portraits of human breast tumours

Author

Koboldt, Daniel C., Fulton, Robert S., McLellan, Michael D., Schmidt, Heather, Kalicki-Veizer, Joelle, McMichael, Joshua F., Fulton, Lucinda L., Dooling, David J., Ding, Li, Mardis, Elaine R., Wilson, Richard K., Ally, Adrian, Balasundaram, Miruna, Butterfield, Yaron S. N., Carlsen, Rebecca, Carter, Candace, Chu, Andy, Chuah, Eric, Chun, Hye-Jung E., Coope, Robin J. N., Dhalla, Noreen, Guin, Ranabir, Hirst, Carrie, Hirst, Martin, Holt, Robert A., Lee, Darlene, Li, Haiyan I., Mayo, Michael, Moore, Richard A., Mungall, Andrew J., Pleasance, Erin, Gordon Robertson, A., Schein, Jacqueline E., Shafiei, Arash, Sipahimalani, Payal, Slobodan, Jared R., Stoll, Dominik, Tam, Angela, Thiessen, Nina, Varhol, Richard J., Wye, Natasja, Zeng, Thomas, Zhao, Yongjun, Birol, Inanc, Jones, Steven J. M., Marra, Marco A., Cherniack, Andrew D., Saksena, Gordon, Onofrio, Robert C., Pho, Nam H., Carter, Scott L., Schumacher, Steven E., Tabak, Barbara, Hernandez, Bryan, Gentry, Jeff, Nguyen, Huy, Crenshaw, Andrew, Ardlie, Kristin, Beroukhim, Rameen, Winckler, Wendy, Getz, Gad, Gabriel, Stacey B., Meyerson, Matthew, Chin, Lynda, Park, Peter J., Kucherlapati, Raju, Hoadley, Katherine A., Todd Auman, J., Fan, Cheng, Turman, Yidi J., Shi, Yan, Li, Ling, Topal, Michael D., He, Xiaping, Chao, Hann-Hsiang, Prat, Aleix, Silva, Grace O., Iglesia, Michael D., Zhao, Wei, Usary, Jerry, Berg, Jonathan S., Adams, Michael, Booker, Jessica, Wu, Junyuan, Gulabani, Anisha, Bodenheimer, Tom, Hoyle, Alan P., Simons, Janae V., Soloway, Matthew G., Mose, Lisle E., Jefferys, Stuart R., Balu, Saianand, Parker, Joel S., Neil Hayes, D., Perou, Charles M., Malik, Simeen, Mahurkar, Swapna, Shen, Hui, Weisenberger, Daniel J., Triche, Timothy, Jr, Lai, Phillip H., Bootwalla, Moiz S., Maglinte, Dennis T., Berman, Benjamin P., Van Den Berg, David J., Baylin, Stephen B., Laird, Peter W., Creighton, Chad J., Donehower, Lawrence A., Noble, Michael, Voet, Doug, Gehlenborg, Nils, DiCara, Daniel, Zhang, Juinhua, Zhang, Hailei, Wu, Chang-Jiun, Liu, Spring Yingchun, Lawrence, Michael S., Zou, Lihua, Sivachenko, Andrey, Lin, Pei, Stojanov, Petar, Jing, Rui, Cho, Juok, Sinha, Raktim, Park, Richard W., Nazaire, Marc-Danie, Robinson, Jim, Thorvaldsdottir, Helga, Mesirov, Jill, Reynolds, Sheila, Kreisberg, Richard B., Bernard, Brady, Bressler, Ryan, Erkkila, Timo, Lin, Jake, Thorsson, Vesteinn, Zhang, Wei, Shmulevich, Ilya, Ciriello, Giovanni, Weinhold, Nils, Schultz, Nikolaus, Gao, Jianjiong, Cerami, Ethan, Gross, Benjamin, Jacobsen, Anders, Sinha, Rileen, Arman Aksoy, B., Antipin, Yevgeniy, Reva, Boris, Shen, Ronglai, Taylor, Barry S., Ladanyi, Marc, Sander, Chris, Anur, Pavana, Spellman, Paul T., Lu, Yiling, Liu, Wenbin, Verhaak, Roel R. G., Mills, Gordon B., Akbani, Rehan, Zhang, Nianxiang, Broom, Bradley M., Casasent, Tod D., Wakefield, Chris, Unruh, Anna K., Baggerly, Keith, Coombes, Kevin, Weinstein, John N., Haussler, David, Benz, Christopher C., Stuart, Joshua M., Benz, Stephen C., Zhu, Jingchun, Szeto, Christopher C., Scott, Gary K., Yau, Christina, Paull, Evan O., Carlin, Daniel, Wong, Christopher, Sokolov, Artem, Thusberg, Janita, Mooney, Sean, Ng, Sam, Goldstein, Theodore C., Ellrott, Kyle, Grifford, Mia, Wilks, Christopher, Ma, Singer, Craft, Brian, Yan, Chunhua, Hu, Ying, Meerzaman, Daoud, Gastier-Foster, Julie M., Bowen, Jay, Ramirez, Nilsa C., Black, Aaron D., Pyatt, Robert E., White, Peter, Zmuda, Erik J., Frick, Jessica, Lichtenberg, Tara M., Brookens, Robin, George, Myra M., Gerken, Mark A., Harper, Hollie A., Leraas, Kristen M., Wise, Lisa J., Tabler, Teresa R., McAllister, Cynthia, Barr, Thomas, Hart-Kothari, Melissa, Tarvin, Katie, Saller, Charles, Sandusky, George, Mitchell, Colleen, Iacocca, Mary V., Brown, Jennifer, Rabeno, Brenda, Czerwinski, Christine, Petrelli, Nicholas, Dolzhansky, Oleg, Abramov, Mikhail, Voronina, Olga, Potapova, Olga, Marks, Jeffrey R., Suchorska, Wiktoria M., Murawa, Dawid, Kycler, Witold, Ibbs, Matthew, Korski, Konstanty, Spychała, Arkadiusz, Murawa, Paweł, Brzeziński, Jacek J., Perz, Hanna, Łaźniak, Radosław, Teresiak, Marek, Tatka, Honorata, Leporowska, Ewa, Bogusz-Czerniewicz, Marta, Malicki, Julian, Mackiewicz, Andrzej, Wiznerowicz, Maciej, Van Le, Xuan, Kohl, Bernard, Viet Tien, Nguyen, Thorp, Richard, Van Bang, Nguyen, Sussman, Howard, Duc Phu, Bui, Hajek, Richard, Phi Hung, Nguyen, Viet The Phuong, Tran, Quyet Thang, Huynh, Zaki Khan, Khurram, Penny, Robert, Mallery, David, Curley, Erin, Shelton, Candace, Yena, Peggy, Ingle, James N., Couch, Fergus J., Lingle, Wilma L., King, Tari A., Maria Gonzalez-Angulo, Ana, Dyer, Mary D., Liu, Shuying, Meng, Xiaolong, Patangan, Modesto, Waldman, Frederic, Stöppler, Hubert, Kimryn Rathmell, W., Thorne, Leigh, Huang, Mei, Boice, Lori, Hill, Ashley, Morrison, Carl, Gaudioso, Carmelo, Bshara, Wiam, Daily, Kelly, Egea, Sophie C., Pegram, Mark D., Gomez-Fernandez, Carmen, Dhir, Rajiv, Bhargava, Rohit, Brufsky, Adam, Shriver, Craig D., Hooke, Jeffrey A., Leigh Campbell, Jamie, Mural, Richard J., Hu, Hai, Somiari, Stella, Larson, Caroline, Deyarmin, Brenda, Kvecher, Leonid, Kovatich, Albert J., Ellis, Matthew J., Stricker, Thomas, White, Kevin, Olopade, Olufunmilayo, Luo, Chunqing, Chen, Yaqin, Bose, Ron, Chang, Li-Wei, Beck, Andrew H., Pihl, Todd, Jensen, Mark, Sfeir, Robert, Kahn, Ari, Chu, Anna, Kothiyal, Prachi, Wang, Zhining, Snyder, Eric, Pontius, Joan, Ayala, Brenda, Backus, Mark, Walton, Jessica, Baboud, Julien, Berton, Dominique, Nicholls, Matthew, Srinivasan, Deepak, Raman, Rohini, Girshik, Stanley, Kigonya, Peter, Alonso, Shelley, Sanbhadti, Rashmi, Barletta, Sean, Pot, David, Sheth, Margi, Demchok, John A., Mills Shaw, Kenna R., Yang, Liming, Eley, Greg, Ferguson, Martin L., Tarnuzzer, Roy W., Zhang, Jiashan, Dillon, Laura A. L., Buetow, Kenneth, Fielding, Peter, Ozenberger, Bradley A., Guyer, Mark S., Sofia, Heidi J., and Palchik, Jacqueline D.

Published
2012
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24. Comprehensive molecular characterization of human colon and rectal cancer

Author

Muzny, Donna M., Bainbridge, Matthew N., Chang, Kyle, Dinh, Huyen H., Drummond, Jennifer A., Fowler, Gerald, Kovar, Christie L., Lewis, Lora R., Morgan, Margaret B., Newsham, Irene F., Reid, Jeffrey G., Santibanez, Jireh, Shinbrot, Eve, Trevino, Lisa R., Wu, Yuan-Qing, Wang, Min, Gunaratne, Preethi, Donehower, Lawrence A., Creighton, Chad J., Wheeler, David A., Gibbs, Richard A., Lawrence, Michael S., Voet, Douglas, Jing, Rui, Cibulskis, Kristian, Sivachenko, Andrey, Stojanov, Petar, McKenna, Aaron, Lander, Eric S., Gabriel, Stacey, Getz, Gad, Ding, Li, Fulton, Robert S., Koboldt, Daniel C., Wylie, Todd, Walker, Jason, Dooling, David J., Fulton, Lucinda, Delehaunty, Kim D., Fronick, Catrina C., Demeter, Ryan, Mardis, Elaine R., Wilson, Richard K., Chu, Andy, Chun, Hye-Jung E., Mungall, Andrew J., Pleasance, Erin, Robertson, Gordon A., Stoll, Dominik, Balasundaram, Miruna, Birol, Inanc, Butterfield, Yaron S. N., Chuah, Eric, Coope, Robin J. N., Dhalla, Noreen, Guin, Ranabir, Hirst, Carrie, Hirst, Martin, Holt, Robert A., Lee, Darlene, Li, Haiyan I., Mayo, Michael, Moore, Richard A., Schein, Jacqueline E., Slobodan, Jared R., Tam, Angela, Thiessen, Nina, Varhol, Richard, Zeng, Thomas, Zhao, Yongjun, Jones, Steven J. M., Marra, Marco A., Bass, Adam J., Ramos, Alex H., Saksena, Gordon, Cherniack, Andrew D., Schumacher, Stephen E., Tabak, Barbara, Carter, Scott L., Pho, Nam H., Nguyen, Huy, Onofrio, Robert C., Crenshaw, Andrew, Ardlie, Kristin, Beroukhim, Rameen, Winckler, Wendy, Meyerson, Matthew, Protopopov, Alexei, Zhang, Juinhua, Hadjipanayis, Angela, Lee, Eunjung, Xi, Ruibin, Yang, Lixing, Ren, Xiaojia, Zhang, Hailei, Sathiamoorthy, Narayanan, Shukla, Sachet, Chen, Peng-Chieh, Haseley, Psalm, Xiao, Yonghong, Lee, Semin, Seidman, Jonathan, Chin, Lynda, Park, Peter J., Kucherlapati, Raju, Auman, Todd J., Hoadley, Katherine A., Du, Ying, Wilkerson, Matthew D., Shi, Yan, Liquori, Christina, Meng, Shaowu, Li, Ling, Turman, Yidi J., Topal, Michael D., Tan, Donghui, Waring, Scot, Buda, Elizabeth, Walsh, Jesse, Jones, Corbin D., Mieczkowski, Piotr A., Singh, Darshan, Wu, Junyuan, Gulabani, Anisha, Dolina, Peter, Bodenheimer, Tom, Hoyle, Alan P., Simons, Janae V., Soloway, Matthew, Mose, Lisle E., Jefferys, Stuart R., Balu, Saianand, O’Connor, Brian D., Prins, Jan F., Chiang, Derek Y., Hayes, Neil D., Perou, Charles M., Hinoue, Toshinori, Weisenberger, Daniel J., Maglinte, Dennis T., Pan, Fei, Berman, Benjamin P., Van Den Berg, David J., Shen, Hui, Triche, Timothy, Jr, Baylin, Stephen B., Laird, Peter W., Noble, Michael, Voet, Doug, Gehlenborg, Nils, DiCara, Daniel, Wu, Chang-Jiun, Yingchun Liu, Spring, Zhou, Lihua, Lin, Pei, Park, Richard W., Nazaire, Marc-Danie, Robinson, Jim, Thorvaldsdottir, Helga, Mesirov, Jill, Thorsson, Vesteinn, Reynolds, Sheila M., Bernard, Brady, Kreisberg, Richard, Lin, Jake, Iype, Lisa, Bressler, Ryan, Erkkilä, Timo, Gundapuneni, Madhumati, Liu, Yuexin, Norberg, Adam, Robinson, Tom, Yang, Da, Zhang, Wei, Shmulevich, Ilya, de Ronde, Jorma J., Schultz, Nikolaus, Cerami, Ethan, Ciriello, Giovanni, Goldberg, Arthur P., Gross, Benjamin, Jacobsen, Anders, Gao, Jianjiong, Kaczkowski, Bogumil, Sinha, Rileen, Aksoy, Arman B., Antipin, Yevgeniy, Reva, Boris, Shen, Ronglai, Taylor, Barry S., Chan, Timothy A., Ladanyi, Marc, Sander, Chris, Akbani, Rehan, Zhang, Nianxiang, Broom, Bradley M., Casasent, Tod, Unruh, Anna, Wakefield, Chris, Hamilton, Stanley R., Cason, Craig R., Baggerly, Keith A., Weinstein, John N., Haussler, David, Benz, Christopher C., Stuart, Joshua M., Benz, Stephen C., Sanborn, Zachary J., Vaske, Charles J., Zhu, Jingchun, Szeto, Christopher, Scott, Gary K., Yau, Christina, Ng, Sam, Goldstein, Ted, Ellrott, Kyle, Collisson, Eric, Cozen, Aaron E., Zerbino, Daniel, Wilks, Christopher, Craft, Brian, Spellman, Paul, Penny, Robert, Shelton, Troy, Hatfield, Martha, Morris, Scott, Yena, Peggy, Shelton, Candace, Sherman, Mark, Paulauskis, Joseph, Gastier-Foster, Julie M., Bowen, Jay, Ramirez, Nilsa C., Black, Aaron, Pyatt, Robert, Wise, Lisa, White, Peter, Bertagnolli, Monica, Brown, Jen, Chu, Gerald C., Czerwinski, Christine, Denstman, Fred, Dhir, Rajiv, Dörner, Arnulf, Fuchs, Charles S., Guillem, Jose G., Iacocca, Mary, Juhl, Hartmut, Kaufman, Andrew, Kohl, Bernard, III, Van Le, Xuan, Mariano, Maria C., Medina, Elizabeth N., Meyers, Michael, Nash, Garrett M., Paty, Phillip B., Petrelli, Nicholas, Rabeno, Brenda, Richards, William G., Solit, David, Swanson, Pat, Temple, Larissa, Tepper, Joel E., Thorp, Richard, Vakiani, Efsevia, Weiser, Martin R., Willis, Joseph E., Witkin, Gary, Zeng, Zhaoshi, Zinner, Michael J., Zornig, Carsten, Jensen, Mark A., Sfeir, Robert, Kahn, Ari B., Chu, Anna L., Kothiyal, Prachi, Wang, Zhining, Snyder, Eric E., Pontius, Joan, Pihl, Todd D., Ayala, Brenda, Backus, Mark, Walton, Jessica, Whitmore, Jon, Baboud, Julien, Berton, Dominique L., Nicholls, Matthew C., Srinivasan, Deepak, Raman, Rohini, Girshik, Stanley, Kigonya, Peter A., Alonso, Shelley, Sanbhadti, Rashmi N., Barletta, Sean P., Greene, John M., Pot, David A., Mills Shaw, Kenna R., Dillon, Laura A. L., Buetow, Ken, Davidsen, Tanja, Demchok, John A., Eley, Greg, Ferguson, Martin, Fielding, Peter, Schaefer, Carl, Sheth, Margi, Yang, Liming, Guyer, Mark S., Ozenberger, Bradley A., Palchik, Jacqueline D., Peterson, Jane, Sofia, Heidi J., and Thomson, Elizabeth

Published
2012
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25. Melanoma genome sequencing reveals frequent PREX2 mutations

Author

Berger, Michael F., Hodis, Eran, Heffernan, Timothy P., Deribe, Yonathan Lissanu, Lawrence, Michael S., Protopopov, Alexei, Ivanova, Elena, Watson, Ian R., Nickerson, Elizabeth, Ghosh, Papia, Zhang, Hailei, Zeid, Rhamy, Ren, Xiaojia, Cibulskis, Kristian, Sivachenko, Andrey Y., Wagle, Nikhil, Sucker, Antje, Sougnez, Carrie, Onofrio, Robert, Ambrogio, Lauren, Auclair, Daniel, Fennell, Timothy, Carter, Scott L., Drier, Yotam, Stojanov, Petar, Singer, Meredith A., Voet, Douglas, Jing, Rui, Saksena, Gordon, Barretina, Jordi, Ramos, Alex H., Pugh, Trevor J., Stransky, Nicolas, Parkin, Melissa, Winckler, Wendy, Mahan, Scott, Ardlie, Kristin, Baldwin, Jennifer, Wargo, Jennifer, Schadendorf, Dirk, Meyerson, Matthew, Gabriel, Stacey B., Golub, Todd R., Wagner, Stephan N., Lander, Eric S., Getz, Gad, Chin, Lynda, and Garraway, Levi A.

Published
2012
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26. Initial genome sequencing and analysis of multiple myeloma

Author

Chapman, Michael A., Lawrence, Michael S., Keats, Jonathan J., Cibulskis, Kristian, Sougnez, Carrie, Schinzel, Anna C., Harview, Christina L., Brunet, Jean-Philippe, Ahmann, Gregory J., Adli, Mazhar, Anderson, Kenneth C., Ardlie, Kristin G., Auclair, Daniel, Baker, Angela, Bergsagel, Leif P., Bernstein, Bradley E., Drier, Yotam, Fonseca, Rafael, Gabriel, Stacey B., Hofmeister, Craig C., Jagannath, Sundar, Jakubowiak, Andrzej J., Krishnan, Amrita, Levy, Joan, Liefeld, Ted, Lonial, Sagar, Mahan, Scott, Mfuko, Bunmi, Monti, Stefano, Perkins, Louise M., Onofrio, Robb, Pugh, Trevor J., Rajkumar, Vincent S., Ramos, Alex H., Siegel, David S., Sivachenko, Andrey, Stewart, Keith A., Trudel, Suzanne, Vij, Ravi, Voet, Douglas, Winckler, Wendy, Zimmerman, Todd, Carpten, John, Trent, Jeff, Hahn, William C., Garraway, Levi A., Meyerson, Matthew, Lander, Eric S., Getz, Gad, and Golub, Todd R.

Published
2011
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27. The genomic complexity of primary human prostate cancer

Author

Berger, Michael F., Lawrence, Michael S., Demichelis, Francesca, Drier, Yotam, Cibulskis, Kristian, Sivachenko, Andrey Y., Sboner, Andrea, Esgueva, Raquel, Pflueger, Dorothee, Sougnez, Carrie, Onofrio, Robert, Carter, Scott L., Park, Kyung, Habegger, Lukas, Ambrogio, Lauren, Fennell, Timothy, Parkin, Melissa, Saksena, Gordon, Voet, Douglas, Ramos, Alex H., Pugh, Trevor J., Wilkinson, Jane, Fisher, Sheila, Winckler, Wendy, Mahan, Scott, Ardlie, Kristin, Baldwin, Jennifer, Simons, Jonathan W., Kitabayashi, Naoki, MacDonald, Theresa Y., Kantoff, Philip W., Chin, Lynda, Gabriel, Stacey B., Gerstein, Mark B., Golub, Todd R., Meyerson, Matthew, Tewari, Ashutosh, Lander, Eric S., Getz, Gad, Rubin, Mark A., and Garraway, Levi A.

Published
2011
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28. The landscape of somatic copy-number alteration across human cancers

Author

Beroukhim, Rameen, Mermel, Craig H., Porter, Dale, Wei, Guo, Raychaudhuri, Soumya, Donovan, Jerry, Barretina, Jordi, Boehm, Jesse S., Dobson, Jennifer, Urashima, Mitsuyoshi, Mc Henry, Kevin T., Pinchback, Reid M., Ligon, Azra H., Cho, Yoon-Jae, Haery, Leila, Greulich, Heidi, Reich, Michael, Winckler, Wendy, Lawrence, Michael S., Weir, Barbara A., Tanaka, Kumiko E., Chiang, Derek Y., Bass, Adam J., Loo, Alice, Hoffman, Carter, Prensner, John, Liefeld, Ted, Gao, Qing, Yecies, Derek, Signoretti, Sabina, Maher, Elizabeth, Kaye, Frederic J., Sasaki, Hidefumi, Tepper, Joel E., Fletcher, Jonathan A., Tabernero, Josep, Baselga, José, Tsao, Ming-Sound, Demichelis, Francesca, Rubin, Mark A., Janne, Pasi A., Daly, Mark J., Nucera, Carmelo, Levine, Ross L., Ebert, Benjamin L., Gabriel, Stacey, Rustgi, Anil K., Antonescu, Cristina R., Ladanyi, Marc, Letai, Anthony, Garraway, Levi A., Loda, Massimo, Beer, David G., True, Lawrence D., Okamoto, Aikou, Pomeroy, Scott L., Singer, Samuel, Golub, Todd R., Lander, Eric S., Getz, Gad, Sellers, William R., and Meyerson, Matthew

Published
2010
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29. Structure of the insulin receptor ectodomain reveals a folded-over conformation

Author

McKern, Neil M., Lawrence, Michael C., Streltsov, Victor A., Lou, Mei-Zhen, Adams, Timothy E., Lovrecz, George O., Elleman, Thomas C., Richards, Kim M., Bentley, John D., Pilling, Patricia A., Hoyne, Peter A., Cartledge, Kellie A., Pham, Tam M., Lewis, Jennifer L., Sankovich, Sonia E., Stoichevska, Violet, Da Silva, Elizabeth, Robinson, Christine P., Frenkel, Maurice J., Sparrow, Lindsay G., Fernley, Ross T., Epa, V. Chandana, and Ward, Colin W.

Published
2006

30. Adhesion through L-selectin requires a threshold hydrodynamic shear

Author

Finger, Erik B., Puri, Kamal D., Alon, Ronen, Lawrence, Michael B., von Andrian, Ulrich H., and Springer, Timothy A.

Subjects
Leukocytes -- Research, Cell adhesion -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Selectin-ligand bonds' high mechanical strength allows it to tether to the vessel wall through one or a few bonds as it also allows rolling in response to hydrodynamic drag. The L-selectin molecule on leukocytes tethers to the peripheral node addressin on the high endothelial venules of the lymph nodes to mediate leukocyte rolling and binds to a ligand on neutrophils to mediate rolling of leukocytes over one another. A mechanism for regulation of these interactions, in vitro and in vivo, is described.

Published
1996

31. Landscape of genomic alterations in cervical carcinomas

Author

Ojesina, Akinyemi I., primary, Lichtenstein, Lee, additional, Freeman, Samuel S., additional, Pedamallu, Chandra Sekhar, additional, Imaz-Rosshandler, Ivan, additional, Pugh, Trevor J., additional, Cherniack, Andrew D., additional, Ambrogio, Lauren, additional, Cibulskis, Kristian, additional, Bertelsen, Bjørn, additional, Romero-Cordoba, Sandra, additional, Treviño, Victor, additional, Vazquez-Santillan, Karla, additional, Guadarrama, Alberto Salido, additional, Wright, Alexi A., additional, Rosenberg, Mara W., additional, Duke, Fujiko, additional, Kaplan, Bethany, additional, Wang, Rui, additional, Nickerson, Elizabeth, additional, Walline, Heather M., additional, Lawrence, Michael S., additional, Stewart, Chip, additional, Carter, Scott L., additional, McKenna, Aaron, additional, Rodriguez-Sanchez, Iram P., additional, Espinosa-Castilla, Magali, additional, Woie, Kathrine, additional, Bjorge, Line, additional, Wik, Elisabeth, additional, Halle, Mari K., additional, Hoivik, Erling A., additional, Krakstad, Camilla, additional, Gabiño, Nayeli Belem, additional, Gómez-Macías, Gabriela Sofia, additional, Valdez-Chapa, Lezmes D., additional, Garza-Rodríguez, María Lourdes, additional, Maytorena, German, additional, Vazquez, Jorge, additional, Rodea, Carlos, additional, Cravioto, Adrian, additional, Cortes, Maria L., additional, Greulich, Heidi, additional, Crum, Christopher P., additional, Neuberg, Donna S., additional, Hidalgo-Miranda, Alfredo, additional, Escareno, Claudia Rangel, additional, Akslen, Lars A., additional, Carey, Thomas E., additional, Vintermyr, Olav K., additional, Gabriel, Stacey B., additional, Barrera-Saldaña, Hugo A., additional, Melendez-Zajgla, Jorge, additional, Getz, Gad, additional, Salvesen, Helga B., additional, and Meyerson, Matthew, additional

Published
2013
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32. Author Correction: Analyses of non-coding somatic drivers in 2,658 cancer whole genomes

Author

Rheinbay, Esther, Nielsen, Morten Muhlig, Abascal, Federico, Wala, Jeremiah A., Shapira, Ofer, Tiao, Grace, Hornshøj, Henrik, Hess, Julian M., Juul, Randi Istrup, Lin, Ziao, Feuerbach, Lars, Sabarinathan, Radhakrishnan, Madsen, Tobias, Kim, Jaegil, Mularoni, Loris, Shuai, Shimin, Lanzós, Andrés, Herrmann, Carl, Maruvka, Yosef E., Shen, Ciyue, Amin, Samirkumar B., Bandopadhayay, Pratiti, Bertl, Johanna, Boroevich, Keith A., Busanovich, John, Carlevaro-Fita, Joana, Chakravarty, Dimple, Chan, Calvin Wing Yiu, Craft, David, Dhingra, Priyanka, Diamanti, Klev, Fonseca, Nuno A., Gonzalez-Perez, Abel, Guo, Qianyun, Hamilton, Mark P., Haradhvala, Nicholas J., Hong, Chen, Isaev, Keren, Johnson, Todd A., Juul, Malene, Kahles, Andre, Kahraman, Abdullah, Kim, Youngwook, Komorowski, Jan, Kumar, Kiran, Kumar, Sushant, Lee, Donghoon, Lehmann, Kjong-Van, Li, Yilong, Liu, Eric Minwei, Lochovsky, Lucas, Park, Keunchil, Pich, Oriol, Roberts, Nicola D., Saksena, Gordon, Schumacher, Steven E., Sidiropoulos, Nikos, Sieverling, Lina, Sinnott-Armstrong, Nasa, Stewart, Chip, Tamborero, David, Tubio, Jose M. C., Umer, Husen M., Uusküla-Reimand, Liis, Wadelius, Claes, Wadi, Lina, Yao, Xiaotong, Zhang, Cheng-Zhong, Zhang, Jing, Haber, James E., Hobolth, Asger, Imielinski, Marcin, Kellis, Manolis, Lawrence, Michael S., von Mering, Christian, Nakagawa, Hidewaki, Raphael, Benjamin J., Rubin, Mark A., Sander, Chris, Stein, Lincoln D., Stuart, Joshua M., Tsunoda, Tatsuhiko, Wheeler, David A., Johnson, Rory, Reimand, Jüri, Gerstein, Mark, Khurana, Ekta, Campbell, Peter J., López-Bigas, Núria, Weischenfeldt, Joachim, Beroukhim, Rameen, Martincorena, Iñigo, Pedersen, Jakob Skou, and Getz, Gad

Published
2023
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33. Somatic mutations affect key pathways in lung adenocarcinoma.

Author

Li Ding, Getz, Gad, Wheeler, David A., Mardis, Elaine R., McLellan, Michael D., Cibulskis, Kristian, Sougnez, Carrie, Greulich, Heidi, Muzny, Donna M., Morgan, Margaret B., Fulton, Lucinda, Fulton, Robert S., Qunyuan Zhang, Wendl, Michael C., Lawrence, Michael S., Larson, David E., Chen, Ken, Dooling, David J., Sabo, Aniko, and Hawes, Alicia C.

Subjects
ADENOCARCINOMA, CANCER, HISTOPATHOLOGY, TUMORS, GENETIC mutation, DNA
Abstract

Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well-classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers—including NF1, APC, RB1 and ATM—and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment. [ABSTRACT FROM AUTHOR]

Published
2008
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