1. All Things in Moderation: Prevention of Intestinal Adenomas by DNA Hypomethylation.

    Cancer Prevention Research 9(7):509 (2016) PMID 27190044

    DNA hypomethylation can prevent intestinal tumorigenesis, presumably by reducing epigenetic silencing of tumor-suppressor genes. A study in this issue by Sheaffer and colleagues challenges this notion by showing that severe DNA hypomethylation by tissue-specific Dnmt1 knockout can actually promo...
  2. Effects of folylpolyglutamate synthase modulation on global and gene-specific DNA methylation and gene expression in human colon and breast cancer cells.

    The Journal of Nutritional Biochemistry 29:27 (2016) PMID 26895662

    Folylpolyglutamate synthase (FPGS) plays a critical role in intracellular folate homeostasis. FPGS-induced polyglutamylated folates are better substrates for several enzymes involved in the generation of S-adenosylmethionine, the primary methyl group donor, and hence FPGS modulation may affect D...
  3. Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma.

    Cell 164(3):550 (2016) PMID 26824661 PMCID PMC4754110

    Therapy development for adult diffuse glioma is hindered by incomplete knowledge of somatic glioma driving alterations and suboptimal disease classification. We defined the complete set of genes associated with 1,122 diffuse grade II-III-IV gliomas from The Cancer Genome Atlas and used molecular...
  4. Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma.
    W Marston Linehan, Paul T Spellman, Christopher J Ricketts, Chad J Creighton, Suzanne Fei, Caleb Davis, David A Wheeler, Bradley A Murray, Laura Schmidt, Cathy D Vocke, Myron Peto, Abu Amar Al Mamun, Eve Shinbrot, Anurag Sethi, Samira Brooks, W Kimryn Rathmell, Angela N Brooks, Katherine A Hoadley, A Gordon Robertson, Denise Brooks, Reanne Bowlby, Sara Sadeghi, Hui Shen, Daniel J Weisenberger, Moiz Bootwalla, Stephen Baylin, Peter W Laird, Andrew D Cherniack, Gordon Saksena, Scott Haake, Jun Li, Han Liang, Yiling Lu, Gordon B Mills, Rehan Akbani, Mark D Leiserson, Benjamin J Raphael, Pavana Anur, Donald Bottaro, Laurence Albiges, Nandita Barnabas, Toni K Choueiri, Bogdan Czerniak, Andrew K Godwin, Ari Hakimi, Thai Ho, James Hsieh, Michael Ittmann, William Y Kim, Bhavani Krishnan, Maria J Merino, Kenna R Mills Shaw, Victor E Reuter, Ed Reznik, Carl Shelley, Brian Shuch, Sabina Signoretti, Ramaprasad Srinivasan, Pheroze Tamboli, George Thomas, Satish Tickoo, Kenneth Burnett, Daniel Crain, Johanna Gardner, Kevin Lau, David Mallery, Scott Morris, Joseph D Paulauskis, Robert J Penny, Candace Shelton, W Troy Shelton, Mark Sherman, Eric Thompson, Peggy Yena, Melissa T Avedon, Jay Bowen, Julie M Gastier-Foster, Mark Gerken, Kristen M Leraas, Tara M Lichtenberg, Nilsa C Ramirez, Tracie Santos, Lisa Wise, Erik Zmuda, John A Demchok, Ina Felau, Carolyn M Hutter, Margi Sheth, Heidi J Sofia, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jean C Zenklusen, Jiashan Zhang, Brenda Ayala, Julien Baboud, Sudha Chudamani, Jia Liu, Laxmi Lolla, Rashi Naresh, Todd Pihl, Qiang Sun, Yunhu Wan, Ye Wu, Adrian Ally, Miruna Balasundaram, Saianand Balu, Rameen Beroukhim, Tom Bodenheimer, Christian Buhay, Yaron S N Butterfield, Rebecca Carlsen, Scott L Carter, Hsu Chao, Eric Chuah, Amanda Clarke, Kyle R Covington, Mahmoud Dahdouli, Ninad Dewal, Noreen Dhalla, Harsha V Doddapaneni, Jennifer A Drummond, Stacey B Gabriel, Richard A Gibbs, Ranabir Guin, Walker Hale, Alicia Hawes, D Neil Hayes, Robert A Holt, Alan P Hoyle, Stuart R Jefferys, Steven M Jones, Corbin D Jones, Divya Kalra, Christie Kovar, Lora Lewis, Jie Li, Yussanne Ma, Marco A Marra, Michael Mayo, Shaowu Meng, Matthew Meyerson, Piotr A Mieczkowski, Richard A Moore, Donna Morton, Lisle E Mose, Andrew J Mungall, Donna Muzny, Joel S Parker, Charles M Perou, Jeffrey Roach, Jacqueline E Schein, Steven E Schumacher, Yan Shi, Janae V Simons, Payal Sipahimalani, Tara Skelly, Matthew G Soloway, Carrie Sougnez, Angela Tam, Donghui Tan, Nina Thiessen, Umadevi Veluvolu, Min Wang, Matthew D Wilkerson, Tina Wong, Junyuan Wu, Liu Xi, Jane Zhou, Jason Bedford, Fengju Chen, Yao Fu, Mark Gerstein, David Haussler, Katayoon Kasaian, Phillip Lai, Shiyun Ling, Amie Radenbaugh, David Van Den Berg, John N Weinstein, Jingchun Zhu, Monique Albert, Iakovina Alexopoulou, Jeremiah Andersen, J Todd Auman, John Bartlett, Sheldon Bastacky, Julie Bergsten, Michael L Blute, Lori Boice, Roni J Bollag, Jeff Boyd, Erik Castle, Ying-Bei Chen, John Cheville, Erin Curley, Benjamin Davies, April DeVolk, Rajiv Dhir, Laura Dike, John Eckman, Jay Engel, Jodi Harr, Ronald Hrebinko, Mei Huang, Lori Huelsenbeck-Dill, Mary Iacocca, Bruce Jacobs, Michael Lobis, Jodi K Maranchie, Scott, Jerome Myers, Joel Nelson, Jeremy Parfitt, Anil Parwani, Nicholas Petrelli, Brenda Rabeno, Somak Roy, Andrew L Salner, Joel Slaton, Melissa Stanton, R Houston Thompson, Leigh Thorne, Kelinda Tucker, Paul M Weinberger, Cynthia Winemiller, Leigh Anne Zach, and Rosemary Zuna

    New England Journal of Medicine 374(2):135 (2016) PMID 26536169 PMCID PMC4775252

    Papillary renal-cell carcinoma, which accounts for 15 to 20% of renal-cell carcinomas, is a heterogeneous disease that consists of various types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is kno...
  5. Promoter Methylation Analysis Reveals That KCNA5 Ion Channel Silencing Supports Ewing Sarcoma Cell Proliferation.

    Molecular Cancer Research 14(1):26 (2016) PMID 26573141 PMCID PMC4716008

    Polycomb proteins are essential regulators of gene expression in stem cells and development. They function to reversibly repress gene transcription via posttranslational modification of histones and chromatin compaction. In many human cancers, genes that are repressed by polycomb in stem cells a...
  6. Clinicopathologic Risk Factor Distributions for MLH1 Promoter Region Methylation in CIMP-Positive Tumors.

    Cancer Epidemiology Biomarkers & Prevention 25(1):68 (2016) PMID 26512054 PMCID PMC4713308

    The CpG island methylator phenotype (CIMP) is a major molecular pathway in colorectal cancer. Approximately 25% to 60% of CIMP tumors are microsatellite unstable (MSI-H) due to DNA hypermethylation of the MLH1 gene promoter. Our aim was to determine if the distributions of clinicopathologic fact...
  7. Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer.

    Cell 163(2):506 (2015) PMID 26451490 PMCID PMC4603750

    Invasive lobular carcinoma (ILC) is the second most prevalent histologic subtype of invasive breast cancer. Here, we comprehensively profiled 817 breast tumors, including 127 ILC, 490 ductal (IDC), and 88 mixed IDC/ILC. Besides E-cadherin loss, the best known ILC genetic hallmark, we identified ...
  8. Tumor Budding in Colorectal Carcinoma: Confirmation of Prognostic Significance and Histologic Cutoff in a Population-based Cohort.

    The American Journal of Surgical Pathology 39(10):1340 (2015) PMID 26200097 PMCID PMC4567920

    Tumor budding in colorectal carcinoma has been associated with poor outcome in multiple studies, but the absence of an established histologic cutoff for "high" tumor budding, heterogeneity in study populations, and varying methods for assessing tumor budding have hindered widespread incorporatio...
  9. Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas.
    Daniel J Brat, Roel G W Verhaak, Kenneth D Aldape, W K Alfred Yung, Sofie R Salama, Lee A D Cooper, Esther Rheinbay, C Ryan Miller, Mark Vitucci, Olena Morozova, A Gordon Robertson, Houtan Noushmehr, Peter W Laird, Andrew D Cherniack, Rehan Akbani, Jason T Huse, Giovanni Ciriello, Laila M Poisson, Jill S Barnholtz-Sloan, Mitchel S Berger, Cameron Brennan, Rivka Colen, Howard Colman, Adam E Flanders, Caterina Giannini, Mia Grifford, Antonio Iavarone, Rajan Jain, Isaac Joseph, Jaegil Kim, Katayoon Kasaian, Tom Mikkelsen, Bradley A Murray, Brian Patrick O'Neill, Lior Pachter, Donald W Parsons, Carrie Sougnez, Erik P Sulman, Scott R Vandenberg, Erwin G Van Meir, Andreas von Deimling, Hailei Zhang, Daniel Crain, Kevin Lau, David Mallery, Scott Morris, Joseph Paulauskis, Robert Penny, Troy Shelton, Mark Sherman, Peggy Yena, Aaron Black, Jay Bowen, Katie Dicostanzo, Julie Gastier-Foster, Kristen M Leraas, Tara M Lichtenberg, Christopher R Pierson, Nilsa C Ramirez, Cynthia Taylor, Stephanie Weaver, Lisa Wise, Erik Zmuda, Tanja Davidsen, John A Demchok, Greg Eley, Martin L Ferguson, Carolyn M Hutter, Kenna R Mills Shaw, Bradley A Ozenberger, Margi Sheth, Heidi J Sofia, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jean Claude Zenklusen, Brenda Ayala, Julien Baboud, Sudha Chudamani, Mark A Jensen, Jia Liu, Todd Pihl, Rohini Raman, Yunhu Wan, Ye Wu, Adrian Ally, J Todd Auman, Miruna Balasundaram, Saianand Balu, Stephen Baylin, Rameen Beroukhim, Moiz S Bootwalla, Reanne Bowlby, Christopher A Bristow, Denise Brooks, Yaron Butterfield, Rebecca Carlsen, Scott Carter, Lynda Chin, Andy Chu, Eric Chuah, Kristian Cibulskis, Amanda Clarke, Simon G Coetzee, Noreen Dhalla, Tim Fennell, Sheila Fisher, Stacey Gabriel, Gad Getz, Richard Gibbs, Ranabir Guin, Angela Hadjipanayis, D Neil Hayes, Toshinori Hinoue, Katherine Hoadley, Robert A Holt, Alan P Hoyle, Stuart R Jefferys, Steven Jones, Corbin D Jones, Raju Kucherlapati, Phillip H Lai, Eric Lander, Semin Lee, Lee Lichtenstein, Yussanne Ma, Dennis T Maglinte, Harshad S Mahadeshwar, Marco A Marra, Michael Mayo, Shaowu Meng, Matthew L Meyerson, Piotr A Mieczkowski, Richard A Moore, Lisle E Mose, Andrew J Mungall, Angeliki Pantazi, Michael Parfenov, Peter J Park, Joel S Parker, Charles M Perou, Alexei Protopopov, Xiaojia Ren, Jeffrey Roach, Thaís Sabedot, Jacqueline Schein, Steven E Schumacher, Jonathan G Seidman, Sahil Seth, Hui Shen, Janae V Simons, Payal Sipahimalani, Matthew G Soloway, Xingzhi Song, Huandong Sun, Barbara Tabak, Angela Tam, Donghui Tan, Jiabin Tang, Nina Thiessen, Timothy Triche, David J Van Den Berg, Umadevi Veluvolu, Scot Waring, Daniel J Weisenberger, Matthew D Wilkerson, Tina Wong, Junyuan Wu, Liu Xi, Andrew W Xu, Lixing Yang, Travis I Zack, Jianhua Zhang, B Arman Aksoy, Harindra Arachchi, Chris Benz, Brady Bernard, Daniel Carlin, Juok Cho, Daniel DiCara, Scott Frazer, Gregory N Fuller, Gao, Nils Gehlenborg, David Haussler, David I Heiman, Lisa Iype, Anders Jacobsen, Zhenlin Ju, Sol Katzman, Hoon Kim, Theo Knijnenburg, Richard Bailey Kreisberg, Michael S Lawrence, William Lee, Kalle Leinonen, Pei Lin, Shiyun Ling, Wenbin Liu, Yingchun Liu, Yuexin Liu, Yiling Lu, Gordon Mills, Sam Ng, Michael S Noble, Evan Paull, Arvind Rao, Sheila Reynolds, Gordon Saksena, Zack Sanborn, Chris Sander, Nikolaus Schultz, Yasin Senbabaoglu, Ronglai Shen, Ilya Shmulevich, Rileen Sinha, Josh Stuart, Onur Sumer, Yichao Sun, Natalie Tasman, Barry S Taylor, Doug Voet, Nils Weinhold, John N Weinstein, Da Yang, Kosuke Yoshihara, Siyuan Zheng, Wei Zhang, Lihua Zou, Ty Abel, Sara Sadeghi, Mark L Cohen, Jenny Eschbacher, Eyas M Hattab, Aditya Raghunathan, Matthew J Schniederjan, Dina Aziz, Gene Barnett, Wendi Barrett, Darell Bigner, Lori Boice, Cathy Brewer, Chiara Calatozzolo, Benito Campos, Carlos Gilberto Carlotti, Timothy A Chan, Lucia Cuppini, Erin Curley, Stefania Cuzzubbo, Karen Devine, Francesco DiMeco, Rebecca Duell, J Bradley Elder, Ashley Fehrenbach, Gaetano Finocchiaro, William Friedman, Jordonna Fulop, Johanna Gardner, Beth Hermes, Christel Herold-Mende, Christine Jungk, Ady Kendler, Norman Lehman, Eric Lipp, Ouida Liu, Randy Mandt, Mary McGraw, Roger Mclendon, Christopher McPherson, Luciano Neder, Phuong Nguyen, Ardene Noss, Raffaele Nunziata, Quinn T Ostrom, Cheryl Palmer, Alessandro Perin, Bianca Pollo, Alexander Potapov, Olga Potapova, W Kimryn Rathmell, Daniil Rotin, Lisa Scarpace, Cathy Schilero, Kelly Senecal, Kristen Shimmel, Vsevolod Shurkhay, Suzanne Sifri, Rosy Singh, Andrew E Sloan, Kathy Smolenski, Susan M Staugaitis, Ruth Steele, Leigh Thorne, Daniela P C Tirapelli, Andreas Unterberg, Mahitha Vallurupalli, Yun Wang, Ronald Warnick, Felicia Williams, Yingli Wolinsky, Sue Bell, Mara Rosenberg, Chip Stewart, Franklin Huang, Jonna L Grimsby, Amie J Radenbaugh, and Jianan Zhang

    New England Journal of Medicine 372(26):2481 (2015) PMID 26061751 PMCID PMC4530011

    Diffuse low-grade and intermediate-grade gliomas (which together make up the lower-grade gliomas, World Health Organization grades II and III) have highly variable clinical behavior that is not adequately predicted on the basis of histologic class. Some are indolent; others quickly progress to g...
  10. Whole-genome and multisector exome sequencing of primary and post-treatment glioblastoma reveals patterns of tumor evolution.

    Genome Research 25(3):316 (2015) PMID 25650244 PMCID PMC4352879

    Glioblastoma (GBM) is a prototypical heterogeneous brain tumor refractory to conventional therapy. A small residual population of cells escapes surgery and chemoradiation, resulting in a typically fatal tumor recurrence ∼ 7 mo after diagnosis. Understanding the molecular architecture of this res...
  11. Association of the colorectal CpG island methylator phenotype with molecular features, risk factors, and family history.

    Cancer Epidemiology Biomarkers & Prevention 24(3):512 (2015) PMID 25587051 PMCID PMC4355081

    The CpG island methylator phenotype (CIMP) represents a subset of colorectal cancers characterized by widespread aberrant DNA hypermethylation at select CpG islands. The risk factors and environmental exposures contributing to etiologic heterogeneity between CIMP and non-CIMP tumors are not know...
  12. Association between molecular subtypes of colorectal cancer and patient survival.

    Gastroenterology 148(1):77 (2015) PMID 25280443 PMCID PMC4274235

    Colorectal cancer (CRC) is a heterogeneous disease that can develop via several pathways. Different CRC subtypes, identified based on tumor markers, have been proposed to reflect these pathways. We evaluated the significance of these previously proposed classifications to survival. Participants ...
  13. Inferring regulatory element landscapes and transcription factor networks from cancer methylomes.

    Genome Biology 16(1):105 (2015) PMID 25994056 PMCID PMC4460959

    Recent studies indicate that DNA methylation can be used to identify transcriptional enhancers, but no systematic approach has been developed for genome-wide identification and analysis of enhancers based on DNA methylation. We describe ELMER (Enhancer Linking by Methylation/Expression Relations...
  14. γ-Glutamyl hydrolase modulation significantly influences global and gene-specific DNA methylation and gene expression in human colon and breast cancer cells.

    Genes & Nutrition 10(1):444 (2015) PMID 25502219 PMCID PMC4265218

    γ-Glutamyl hydrolase (GGH) plays an important role in folate homeostasis by catalyzing hydrolysis of polyglutamylated folate into monoglutamates. Polyglutamylated folates are better substrates for several enzymes involved in the generation of S-adenosylmethionine, the primary methyl group donor,...
  15. The somatic genomic landscape of chromophobe renal cell carcinoma.

    Cancer Cell 26(3):319 (2014) PMID 25155756 PMCID PMC4160352

    We describe the landscape of somatic genomic alterations of 66 chromophobe renal cell carcinomas (ChRCCs) on the basis of multidimensional and comprehensive characterization, including mtDNA and whole-genome sequencing. The result is consistent that ChRCC originates from the distal nephron compa...
  16. Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin.

    Cell 158(4):929 (2014) PMID 25109877 PMCID PMC4152462

    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 ...
  17. Multiscale representation of genomic signals.

    Nature Methods 11(6):689 (2014) PMID 24727652 PMCID PMC4040162

    Genomic information is encoded on a wide range of distance scales, ranging from tens of bases to megabases. We developed a multiscale framework to analyze and visualize the information content of genomic signals. Different types of signals, such as G+C content or DNA methylation, are characteriz...
  18. Abstract 31: DNA methylation analysis of radiated skin reveals chonic inflammation with a predominance of polymorphonuclear granulocytes.

    Plastic &amp Reconstructive Surgery 133(3 Suppl):42 (2014) PMID 25942142

  19. Non-specific filtering of beta-distributed data.

    BMC Bioinformatics 15:199 (2014) PMID 24943962 PMCID PMC4230495

    Non-specific feature selection is a dimension reduction procedure performed prior to cluster analysis of high dimensional molecular data. Not all measured features are expected to show biological variation, so only the most varying are selected for analysis. In DNA methylation studies, DNA methy...
  20. An epidemiologic and genomic investigation into the obesity paradox in renal cell carcinoma.

    JNCI Journal of the National Cancer Institute 105(24):1862 (2013) PMID 24285872 PMCID PMC3866155

    Obesity increases risk for clear-cell renal cell carcinoma (ccRCC), yet obese patients appear to experience longer survival than nonobese patients. We examined body mass index (BMI) in relation to stage, grade, and cancer-specific mortality (CSM) while considering detection bias, nutritional sta...