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5 results on '"Freeman, Samuel S."'

1. Genomic Heterogeneity as a Barrier to Precision Medicine in Gastroesophageal Adenocarcinoma

Author

Pectasides, Eirini, Stachler, Matthew D, Derks, Sarah, Liu, Yang, Maron, Steven, Islam, Mirazul, Alpert, Lindsay, Kwak, Heewon, Kindler, Hedy, Polite, Blase, Sharma, Manish R, Allen, Kenisha, O'Day, Emily, Lomnicki, Samantha, Maranto, Melissa, Kanteti, Rajani, Fitzpatrick, Carrie, Weber, Christopher, Setia, Namrata, Xiao, Shu-Yuan, Hart, John, Nagy, Rebecca J, Kim, Kyoung-Mee, Choi, Min-Gew, Min, Byung-Hoon, Nason, Katie S, O'Keefe, Lea, Watanabe, Masayuki, Baba, Hideo, Lanman, Rick, Agoston, Agoston T, Oh, David J, Dunford, Andrew, Thorner, Aaron R, Ducar, Matthew D, Wollison, Bruce M, Coleman, Haley A, Ji, Yuan, Posner, Mitchell C, Roggin, Kevin, Turaga, Kiran, Chang, Paul, Hogarth, Kyle, Siddiqui, Uzma, Gelrud, Andres, Ha, Gavin, Freeman, Samuel S, Rhoades, Justin, Reed, Sarah, Gydush, Greg, Rotem, Denisse, Davison, Jon, Imamura, Yu, Adalsteinsson, Viktor, Lee, Jeeyun, Bass, Adam J, and Catenacci, Daniel V

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Clinical Sciences, Oncology and Carcinogenesis, Digestive Diseases, Cancer, Human Genome, Genetic Testing, Good Health and Well Being, Adenocarcinoma, Cohort Studies, Esophageal Neoplasms, Genomics, Humans, Precision Medicine, Stomach Neoplasms, Exome Sequencing, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

Gastroesophageal adenocarcinoma (GEA) is a lethal disease where targeted therapies, even when guided by genomic biomarkers, have had limited efficacy. A potential reason for the failure of such therapies is that genomic profiling results could commonly differ between the primary and metastatic tumors. To evaluate genomic heterogeneity, we sequenced paired primary GEA and synchronous metastatic lesions across multiple cohorts, finding extensive differences in genomic alterations, including discrepancies in potentially clinically relevant alterations. Multiregion sequencing showed significant discrepancy within the primary tumor (PT) and between the PT and disseminated disease, with oncogene amplification profiles commonly discordant. In addition, a pilot analysis of cell-free DNA (cfDNA) sequencing demonstrated the feasibility of detecting genomic amplifications not detected in PT sampling. Lastly, we profiled paired primary tumors, metastatic tumors, and cfDNA from patients enrolled in the personalized antibodies for GEA (PANGEA) trial of targeted therapies in GEA and found that genomic biomarkers were recurrently discrepant between the PT and untreated metastases. Divergent primary and metastatic tissue profiling led to treatment reassignment in 32% (9/28) of patients. In discordant primary and metastatic lesions, we found 87.5% concordance for targetable alterations in metastatic tissue and cfDNA, suggesting the potential for cfDNA profiling to enhance selection of therapy.Significance: We demonstrate frequent baseline heterogeneity in targetable genomic alterations in GEA, indicating that current tissue sampling practices for biomarker testing do not effectively guide precision medicine in this disease and that routine profiling of metastatic lesions and/or cfDNA should be systematically evaluated. Cancer Discov; 8(1); 37-48. ©2017 AACR.See related commentary by Sundar and Tan, p. 14See related article by Janjigian et al., p. 49This article is highlighted in the In This Issue feature, p. 1.

Published
2018

2. Transcriptomic Characterization of SF3B1 Mutation Reveals Its Pleiotropic Effects in Chronic Lymphocytic Leukemia

Author

Wang, Lili, Brooks, Angela N, Fan, Jean, Wan, Youzhong, Gambe, Rutendo, Li, Shuqiang, Hergert, Sarah, Yin, Shanye, Freeman, Samuel S, Levin, Joshua Z, Fan, Lin, Seiler, Michael, Buonamici, Silvia, Smith, Peter G, Chau, Kevin F, Cibulskis, Carrie L, Zhang, Wandi, Rassenti, Laura Z, Ghia, Emanuela M, Kipps, Thomas J, Fernandes, Stacey, Bloch, Donald B, Kotliar, Dylan, Landau, Dan A, Shukla, Sachet A, Aster, Jon C, Reed, Robin, DeLuca, David S, Brown, Jennifer R, Neuberg, Donna, Getz, Gad, Livak, Kenneth J, Meyerson, Matthew M, Kharchenko, Peter V, and Wu, Catherine J

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Clinical Research, Hematology, Lymphatic Research, Human Genome, Genetics, Rare Diseases, Cancer, Lymphoma, 2.1 Biological and endogenous factors, Alternative Splicing, Cell Line, Tumor, Dishevelled Proteins, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Mutation, Phosphoproteins, RNA Splicing Factors, Receptors, Notch, Signal Transduction, CLL, Notch signaling, RNA sequencing, SF3B1, alternative splicing, Neurosciences, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

Mutations in SF3B1, which encodes a spliceosome component, are associated with poor outcome in chronic lymphocytic leukemia (CLL), but how these contribute to CLL progression remains poorly understood. We undertook a transcriptomic characterization of primary human CLL cells to identify transcripts and pathways affected by SF3B1 mutation. Splicing alterations, identified in the analysis of bulk cells, were confirmed in single SF3B1-mutated CLL cells and also found in cell lines ectopically expressing mutant SF3B1. SF3B1 mutation was found to dysregulate multiple cellular functions including DNA damage response, telomere maintenance, and Notch signaling (mediated through KLF8 upregulation, increased TERC and TERT expression, or altered splicing of DVL2 transcript, respectively). SF3B1 mutation leads to diverse changes in CLL-related pathways.

Published
2016

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

Author

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

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

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

Published
2014

4. The Cancer Genome Atlas Pan-Cancer analysis project

Author

Chang, Kyle, Creighton, Chad J, Davis, Caleb, Donehower, Lawrence, Drummond, Jennifer, Wheeler, David, Ally, Adrian, Balasundaram, Miruna, Birol, Inanc, Butterfield, Yaron SN, Chu, Andy, Chuah, Eric, Chun, Hye-Jung E, Dhalla, Noreen, Guin, Ranabir, Hirst, Martin, Hirst, Carrie, Holt, Robert A, Jones, Steven JM, Lee, Darlene, Li, Haiyan I, Marra, Marco A, Mayo, Michael, Moore, Richard A, Mungall, Andrew J, Robertson, A Gordon, Schein, Jacqueline E, Sipahimalani, Payal, Tam, Angela, Thiessen, Nina, Varhol, Richard J, Beroukhim, Rameen, Bhatt, Ami S, Brooks, Angela N, Cherniack, Andrew D, Freeman, Samuel S, Gabriel, Stacey B, Helman, Elena, Jung, Joonil, Meyerson, Matthew, Ojesina, Akinyemi I, Pedamallu, Chandra Sekhar, Saksena, Gordon, Schumacher, Steven E, Tabak, Barbara, Zack, Travis, Lander, Eric S, Bristow, Christopher A, Hadjipanayis, Angela, Haseley, Psalm, Kucherlapati, Raju, Lee, Semin, Lee, Eunjung, Luquette, Lovelace J, Mahadeshwar, Harshad S, Pantazi, Angeliki, Parfenov, Michael, Park, Peter J, Protopopov, Alexei, Ren, Xiaojia, Santoso, Netty, Seidman, Jonathan, Seth, Sahil, Song, Xingzhi, Tang, Jiabin, Xi, Ruibin, Xu, Andrew W, Yang, Lixing, Zeng, Dong, Auman, J Todd, Balu, Saianand, Buda, Elizabeth, Fan, Cheng, Hoadley, Katherine A, Jones, Corbin D, Meng, Shaowu, Mieczkowski, Piotr A, Parker, Joel S, Perou, Charles M, Roach, Jeffrey, Shi, Yan, Silva, Grace O, Tan, Donghui, Veluvolu, Umadevi, Waring, Scot, Wilkerson, Matthew D, Wu, Junyuan, Zhao, Wei, Bodenheimer, Tom, Hayes, D Neil, Hoyle, Alan P, Jeffreys, Stuart R, Mose, Lisle E, Simons, Janae V, Soloway, Mathew G, Baylin, Stephen B, Berman, Benjamin P, Bootwalla, Moiz S, Danilova, Ludmila, and Herman, James G

Subjects
Biological Sciences, Genetics, Precision Medicine, Human Genome, Cancer Genomics, Cancer, Good Health and Well Being, Gene Expression Profiling, Genome, Humans, Neoplasms, Cancer Genome Atlas Research Network, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile.

Published
2013

5. Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin

Author

Hoadley, Katherine A., Yau, Christina, Wolf, Denise M., Cherniack, Andrew D., Tamborero, David, Sam, Ng, Leiserson, Max D. M., Niu, Beifang, Mclellan, Michael D., Uzunangelov, Vladislav, Zhang, Jiashan, Kandoth, Cyriac, Akbani, Rehan, Shen, Hui, Omberg, Larsson, Chu, Andy, Margolin, Adam A., Van'T Veer, Laura J., Lopez Bigas, Nuria, Laird, Peter W., Raphael, Benjamin J., Ding, Li, Robertson, A. Gordon, Byers, Lauren A., Mills, Gordon B., Weinstein, John N., Van Waes, Carter, Chen, Zhong, Collisson, Eric A., Benz, Christopher C, Perou, Charles M., Stuart, Joshua M., Rachel, Abbott, Scott, Abbott, Arman Aksoy, B., Kenneth, Aldape, Adrian, Ally, Samirku mar Amin, Dimitris, Anastassiou, Todd Auman, J., Baggerly, Keith A., Miruna, Balasundaram, Saianand, Balu, Baylin, Stephen B., Benz, Stephen C., Berman, Benjamin P., Brady, Bernard, Bhatt, Ami S., Inanc, Birol, Black, Aaron D., Tom, Bodenheimer, Bootwalla, Moiz S., Jay, Bowen, Ryan, Bressler, Bristow, Christopher A., Brooks, Angela N., Bradley, Broom, Elizabeth, Buda, Robert, Burton, Butterfield, Yaron S. N., Daniel, Carlin, Carter, Scott L., Casasent, Tod D., Kyle, Chang, Stephen, Chanock, Lynda, Chin, Dong Yeon Cho, Juok, Cho, Eric, Chuah, Chun, Hye Jung E., Kristian, Cibulskis, Giovanni, Ciriello, James Cle land, Melisssa, Cline, Brian, Craft, Creighton, Chad J., Ludmila, Danilova, Tanja, Davidsen, Caleb, Davis, Dees, Nathan D., Kim, Delehaunty, Demchok, John A., Noreen, Dhalla, Daniel, Dicara, Huyen, Dinh, Dobson, Jason R., Deepti, Dodda, Harshavardhan, Doddapaneni, Lawrence, Donehower, Dooling, David J., Gideon, Dresdner, Jennifer, Drummond, Andrea, Eakin, Mary, Edgerton, Eldred, Jim M., Greg, Eley, Kyle, Ellrott, Cheng, Fan, Suzanne, Fei, Ina, Felau, Scott, Frazer, Freeman, Samuel S., Jessica, Frick, Fronick, Catrina C., Ful ton, Lucinda L., Robert, Fulton, Gabriel, Stacey B., Jianjiong, Gao, Gastier Foster, Julie M., Nils, Gehlenborg, Myra, George, Gad, Getz, Richard, Gibbs, Mary, Goldman, Abel Gonzalez Perez, Benjamin, Gross, Ranabir, Guin, Preethi, Gunaratne, Angela, Hadjipanayis, Hamilton, Mark P., Hamilton, Stanley R., Leng, Han, Han, Yi, Harper, Hollie A., Psalm, Haseley, David, Haussler, Neil Hayes, D., Heiman, David I., Elena, Helman, Carmen, Helsel, Herbrich, Shelley M., Her man, James G., Toshinori, Hinoue, Carrie, Hirst, Martin, Hirst, Holt, Robert A., Hoyle, Alan P., Lisa, Iype, Anders, Jacobsen, Jeffreys, Stuart R., Jensen, Mark A., Jones, Corbin D., Jones, Steven J. M., Zhenlin, Ju, Joonil, Jung, Andre, Kahles, Ari, Kahn, Joelle Kalicki Veizer, Divya, Kalra, Krishna Latha Kanchi, Kane, David W., Hoon, Kim, Jaegil, Kim, Theo, Knijnenburg, Koboldt, Daniel C., Christie, Kovar, Roger, Kramer, Richard, Kreisberg, Raju, Kucherlapati, Marc, Ladanyi, Lander, Eric S., Larson, David E., Lawrence, Michael S., Darlene, Lee, Eunjung, Lee, Semin, Lee, William, Lee, Kjong Van Lehmann, Kalle, Leinonen, Ler aas, Kristen M., Seth, Lerner, Levine, Douglas A., Lora, Lewis, Ley, Timothy J., Haiyan I., Li, Jun, Li, Wei, Li, Han, Liang, Lichtenberg, Tara M., Jake, Lin, Ling, Lin, Pei, Lin, Wen bin Liu, Yingchun, Liu, Yuexin, Liu, Lorenzi, Philip L., Charles, Lu, Yiling, Lu, Luquette, Love lace J., Singer, Ma, Magrini, Vincent J., Mahadeshwar, Harshad S., Mardis, Elaine R., Adam, Margolin, Marra, Marco A., Michael, Mayo, Cynthia, Mcallister, Mcguire, Sean E., Mcmichael, Joshua F., James, Melott, Shaowu, Meng, Matthew, Meyerson, Mieczkowski, Piotr A., Miller, Christopher A., Miller, Martin L., Michael, Miller, Moore, Richard A., Margaret, Morgan, Donna, Morton, Mose, Lisle E., Mungall, Andrew J., Donna, Muzny, Lam, Nguyen, Noble, Michael S., Houtan, Noushmehr, Michelle, O’Laughlin, Ojesina, Akinyemi I., Tai Hsien Ou Yang, Brad, Ozenberger, Angeliki, Pantazi, Michael, Parfenov, Park, Peter J., Parker, Joel S., Evan, Paull, Chandra Sekhar Pedamallu, Todd, Pihl, Craig, Pohl, David, Pot, Alexei, Protopopov, Teresa, Przytycka, Amie Raden baugh, Ramirez, Nilsa C., Ricardo, Ramirez, Gunnar Ra, ̈ tsch, Jeffrey, Reid, Xiao jia Ren, Boris, Reva, Reynolds, Sheila M., Rhie, Suhn K., Jeffrey, Roach, Hector, Rovira, Michael, Ryan, Gordon, Saksena, Sofie, Salama, Chris, Sander, Netty, Santoso, Schein, Jacqueline E., Heather, Schmidt, Nikolaus, Schultz, Schumacher, Steven E., Jonathan, Seidman, Yasin, Senbabaoglu, Sahil, Seth, Saman tha Sharpe, Ronglai, Shen, Margi, Sheth, Yan, Shi, Ilya, Shmulevich, Silva, Grace O., Simons, Janae V., Rileen, Sinha, Payal, Sipahimalani, Smith, Scott M., Sofia, Heidi J., Artem, Sokolov, Soloway, Mathew G., Xingzhi, Song, Carrie Soug nez, Paul, Spellman, Louis, Staudt, Chip, Stewart, Petar, Stojanov, Xiaoping, Su, Onur Sumer, S., Yichao, Sun, Teresa, Swatloski, Barbara, Tabak, Angela, Tam, Donghui, Tan, Jiabin, Tang, Roy, Tarnuzzer, Taylor, Barry S., Nina, Thiessen, Ves teinn Thorsson, Timothy Triche, J. r., Van Den Berg, David J., Vandin, Fabio, Varhol, Richard J., Vaske, Charles J., Umadevi, Veluvolu, Roeland, Verhaak, Doug, Voet, Jason, Walker, Wallis, John W., Peter, Waltman, Yunhu, Wan, Min, Wang, Wenyi, Wang, Zhining, Wang, Scot, Waring, Nils, Weinhold, Weisenberger, Daniel J., Wendl, Michael C., David, Wheeler, Wilkerson, Matthew D., Wilson, Richard K., Lisa, Wise, Andrew, Wong, Chang Jiun Wu, Chia Chin Wu, Hsin Ta Wu, Junyuan, Wu, Todd, Wylie, Liu, Xi, Ruibin, Xi, Zheng, Xia, Andrew W., Xu, Yang, Da, Liming, Yang, Lixing, Yang, Yang, Yang, Jun, Yao, Rong, Yao, Kai, Ye, Ko suke Yoshihara, Yuan, Yuan, Yung, Alfred K., Travis, Zack, Dong, Zeng, Jean Claude Zenklusen, Hailei, Zhang, Jianhua, Zhang, Nianxiang, Zhang, Qunyuan, Zhang, Wei, Zhang, Wei, Zhao, Siyuan, Zheng, Jing, Zhu, Erik, Zmuda, and Lihua, Zou

Subjects
Genetics and Molecular Biology (all), Cluster Analysis, Humans, Neoplasms, Transcriptome, Biochemistry, Genetics and Molecular Biology (all), Extramural, Biochemistry, Genetics and Molecular Biology(all), Cancer, Computational biology, Disease, Biology, medicine.disease, Bioinformatics, Biochemistry, General Biochemistry, Genetics and Molecular Biology, Article, 3. Good health, Molecular classification, TP63, CLUSTERS (ANÁLISE), medicine, Head and neck, Gene
Abstract

Summary Recent genomic analyses of pathologically defined tumor types identify "within-a-tissue" disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform on 3,527 specimens from 12 cancer types, revealing a unified classification into 11 major subtypes. Five subtypes were nearly identical to their tissue-of-origin counterparts, but several distinct cancer types were found to converge into common subtypes. Lung squamous, head and neck, and a subset of bladder cancers coalesced into one subtype typified by TP53 alterations, TP63 amplifications, and high expression of immune and proliferation pathway genes. Of note, bladder cancers split into three pan-cancer subtypes. The multiplatform classification, while correlated with tissue-of-origin, provides independent information for predicting clinical outcomes. All data sets are available for data-mining from a unified resource to support further biological discoveries and insights into novel therapeutic strategies.

Published
2014
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