Author: "Fulton, Lucinda L." - Searchworks@Jio Institute Digital Library Search Results

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145 results on '"Fulton, Lucinda L."'

1. A draft human pangenome reference

Author: Liao, Wen-Wei, Asri, Mobin, Ebler, Jana, Doerr, Daniel, Haukness, Marina, Hickey, Glenn, Lu, Shuangjia, Lucas, Julian K, Monlong, Jean, Abel, Haley J, Buonaiuto, Silvia, Chang, Xian H, Cheng, Haoyu, Chu, Justin, Colonna, Vincenza, Eizenga, Jordan M, Feng, Xiaowen, Fischer, Christian, Fulton, Robert S, Garg, Shilpa, Groza, Cristian, Guarracino, Andrea, Harvey, William T, Heumos, Simon, Howe, Kerstin, Jain, Miten, Lu, Tsung-Yu, Markello, Charles, Martin, Fergal J, Mitchell, Matthew W, Munson, Katherine M, Mwaniki, Moses Njagi, Novak, Adam M, Olsen, Hugh E, Pesout, Trevor, Porubsky, David, Prins, Pjotr, Sibbesen, Jonas A, Sirén, Jouni, Tomlinson, Chad, Villani, Flavia, Vollger, Mitchell R, Antonacci-Fulton, Lucinda L, Baid, Gunjan, Baker, Carl A, Belyaeva, Anastasiya, Billis, Konstantinos, Carroll, Andrew, Chang, Pi-Chuan, Cody, Sarah, Cook, Daniel E, Cook-Deegan, Robert M, Cornejo, Omar E, Diekhans, Mark, Ebert, Peter, Fairley, Susan, Fedrigo, Olivier, Felsenfeld, Adam L, Formenti, Giulio, Frankish, Adam, Gao, Yan, Garrison, Nanibaa’ A, Giron, Carlos Garcia, Green, Richard E, Haggerty, Leanne, Hoekzema, Kendra, Hourlier, Thibaut, Ji, Hanlee P, Kenny, Eimear E, Koenig, Barbara A, Kolesnikov, Alexey, Korbel, Jan O, Kordosky, Jennifer, Koren, Sergey, Lee, HoJoon, Lewis, Alexandra P, Magalhães, Hugo, Marco-Sola, Santiago, Marijon, Pierre, McCartney, Ann, McDaniel, Jennifer, Mountcastle, Jacquelyn, Nattestad, Maria, Nurk, Sergey, Olson, Nathan D, Popejoy, Alice B, Puiu, Daniela, Rautiainen, Mikko, Regier, Allison A, Rhie, Arang, Sacco, Samuel, Sanders, Ashley D, Schneider, Valerie A, Schultz, Baergen I, Shafin, Kishwar, Smith, Michael W, Sofia, Heidi J, Abou Tayoun, Ahmad N, Thibaud-Nissen, Françoise, and Tricomi, Francesca Floriana
Subjects: Biological Sciences, Genetics, 2.1 Biological and endogenous factors, 1.5 Resources and infrastructure (underpinning), Generic health relevance, Humans, Diploidy, Genome, Human, Haplotypes, Sequence Analysis, DNA, Genomics, Reference Standards, Cohort Studies, Alleles, Genetic Variation, General Science & Technology
Abstract: Here the Human Pangenome Reference Consortium presents a first draft of the human pangenome reference. The pangenome contains 47 phased, diploid assemblies from a cohort of genetically diverse individuals1. These assemblies cover more than 99% of the expected sequence in each genome and are more than 99% accurate at the structural and base pair levels. Based on alignments of the assemblies, we generate a draft pangenome that captures known variants and haplotypes and reveals new alleles at structurally complex loci. We also add 119 million base pairs of euchromatic polymorphic sequences and 1,115 gene duplications relative to the existing reference GRCh38. Roughly 90 million of the additional base pairs are derived from structural variation. Using our draft pangenome to analyse short-read data reduced small variant discovery errors by 34% and increased the number of structural variants detected per haplotype by 104% compared with GRCh38-based workflows, which enabled the typing of the vast majority of structural variant alleles per sample.
Published: 2023

2. Gaps and complex structurally variant loci in phased genome assemblies

Author: Porubsky, David, Vollger, Mitchell R, Harvey, William T, Rozanski, Allison N, Ebert, Peter, Hickey, Glenn, Hasenfeld, Patrick, Sanders, Ashley D, Stober, Catherine, Consortium, Human Pangenome Reference, Korbel, Jan O, Paten, Benedict, Marschall, Tobias, Eichler, Evan E, Abel, Haley J, Antonacci-Fulton, Lucinda L, Asri, Mobin, Baid, Gunjan, Baker, Carl A, Belyaeva, Anastasiya, Billis, Konstantinos, Bourque, Guillaume, Buonaiuto, Silvia, Carroll, Andrew, Chaisson, Mark JP, Chang, Pi-Chuan, Chang, Xian H, Cheng, Haoyu, Chu, Justin, Cody, Sarah, Colonna, Vincenza, Cook, Daniel E, Cook-Deegan, Robert M, Cornejo, Omar E, Diekhans, Mark, Doerr, Daniel, Ebler, Jana, Eizenga, Jordan M, Fairley, Susan, Fedrigo, Olivier, Felsenfeld, Adam L, Feng, Xiaowen, Fischer, Christian, Flicek, Paul, Formenti, Giulio, Frankish, Adam, Fulton, Robert S, Gao, Yan, Garg, Shilpa, Garrison, Erik, Garrison, Nanibaa’ A, Giron, Carlos Garcia, Green, Richard E, Groza, Cristian, Guarracino, Andrea, Haggerty, Leanne, Hall, Ira M, Haukness, Marina, Haussler, David, Heumos, Simon, Hoekzema, Kendra, Hourlier, Thibaut, Howe, Kerstin, Jain, Miten, Jarvis, Erich D, Ji, Hanlee P, Kenny, Eimear E, Koenig, Barbara A, Kolesnikov, Alexey, Kordosky, Jennifer, Koren, Sergey, Lee, HoJoon, Lewis, Alexandra P, Li, Heng, Liao, Wen-Wei, Lu, Shuangjia, Lu, Tsung-Yu, Lucas, Julian K, Magalhães, Hugo, Marco-Sola, Santiago, Marijon, Pierre, Markello, Charles, Martin, Fergal J, McCartney, Ann, McDaniel, Jennifer, Miga, Karen H, Mitchell, Matthew W, Monlong, Jean, Mountcastle, Jacquelyn, Munson, Katherine M, Mwaniki, Moses Njagi, Nattestad, Maria, Novak, Adam M, and Nurk, Sergey
Subjects: Biological Sciences, Bioinformatics and Computational Biology, Genetics, Human Genome, Humans, DNA, Satellite, Polymorphism, Genetic, Haplotypes, Segmental Duplications, Genomic, Sequence Analysis, DNA, Human Pangenome Reference Consortium, Medical and Health Sciences, Bioinformatics
Abstract: There has been tremendous progress in phased genome assembly production by combining long-read data with parental information or linked-read data. Nevertheless, a typical phased genome assembly generated by trio-hifiasm still generates more than 140 gaps. We perform a detailed analysis of gaps, assembly breaks, and misorientations from 182 haploid assemblies obtained from a diversity panel of 77 unique human samples. Although trio-based approaches using HiFi are the current gold standard, chromosome-wide phasing accuracy is comparable when using Strand-seq instead of parental data. Importantly, the majority of assembly gaps cluster near the largest and most identical repeats (including segmental duplications [35.4%], satellite DNA [22.3%], or regions enriched in GA/AT-rich DNA [27.4%]). Consequently, 1513 protein-coding genes overlap assembly gaps in at least one haplotype, and 231 are recurrently disrupted or missing from five or more haplotypes. Furthermore, we estimate that 6-7 Mbp of DNA are misorientated per haplotype irrespective of whether trio-free or trio-based approaches are used. Of these misorientations, 81% correspond to bona fide large inversion polymorphisms in the human species, most of which are flanked by large segmental duplications. We also identify large-scale alignment discontinuities consistent with 11.9 Mbp of deletions and 161.4 Mbp of insertions per haploid genome. Although 99% of this variation corresponds to satellite DNA, we identify 230 regions of euchromatic DNA with frequent expansions and contractions, nearly half of which overlap with 197 protein-coding genes. Such variable and incompletely assembled regions are important targets for future algorithmic development and pangenome representation.
Published: 2023

3. Semi-automated assembly of high-quality diploid human reference genomes

Author: Jarvis, Erich D, Formenti, Giulio, Rhie, Arang, Guarracino, Andrea, Yang, Chentao, Wood, Jonathan, Tracey, Alan, Thibaud-Nissen, Francoise, Vollger, Mitchell R, Porubsky, David, Cheng, Haoyu, Asri, Mobin, Logsdon, Glennis A, Carnevali, Paolo, Chaisson, Mark JP, Chin, Chen-Shan, Cody, Sarah, Collins, Joanna, Ebert, Peter, Escalona, Merly, Fedrigo, Olivier, Fulton, Robert S, Fulton, Lucinda L, Garg, Shilpa, Gerton, Jennifer L, Ghurye, Jay, Granat, Anastasiya, Green, Richard E, Harvey, William, Hasenfeld, Patrick, Hastie, Alex, Haukness, Marina, Jaeger, Erich B, Jain, Miten, Kirsche, Melanie, Kolmogorov, Mikhail, Korbel, Jan O, Koren, Sergey, Korlach, Jonas, Lee, Joyce, Li, Daofeng, Lindsay, Tina, Lucas, Julian, Luo, Feng, Marschall, Tobias, Mitchell, Matthew W, McDaniel, Jennifer, Nie, Fan, Olsen, Hugh E, Olson, Nathan D, Pesout, Trevor, Potapova, Tamara, Puiu, Daniela, Regier, Allison, Ruan, Jue, Salzberg, Steven L, Sanders, Ashley D, Schatz, Michael C, Schmitt, Anthony, Schneider, Valerie A, Selvaraj, Siddarth, Shafin, Kishwar, Shumate, Alaina, Stitziel, Nathan O, Stober, Catherine, Torrance, James, Wagner, Justin, Wang, Jianxin, Wenger, Aaron, Xiao, Chuanle, Zimin, Aleksey V, Zhang, Guojie, Wang, Ting, Li, Heng, Garrison, Erik, Haussler, David, Hall, Ira, Zook, Justin M, Eichler, Evan E, Phillippy, Adam M, Paten, Benedict, Howe, Kerstin, and Miga, Karen H
Subjects: Genetics, Human Genome, Biotechnology, Generic health relevance, Humans, Chromosome Mapping, Diploidy, Genome, Human, Haplotypes, High-Throughput Nucleotide Sequencing, Sequence Analysis, DNA, Reference Standards, Genomics, Chromosomes, Human, Genetic Variation, Human Pangenome Reference Consortium, General Science & Technology
Abstract: The current human reference genome, GRCh38, represents over 20 years of effort to generate a high-quality assembly, which has benefitted society1,2. However, it still has many gaps and errors, and does not represent a biological genome as it is a blend of multiple individuals3,4. Recently, a high-quality telomere-to-telomere reference, CHM13, was generated with the latest long-read technologies, but it was derived from a hydatidiform mole cell line with a nearly homozygous genome5. To address these limitations, the Human Pangenome Reference Consortium formed with the goal of creating high-quality, cost-effective, diploid genome assemblies for a pangenome reference that represents human genetic diversity6. Here, in our first scientific report, we determined which combination of current genome sequencing and assembly approaches yield the most complete and accurate diploid genome assembly with minimal manual curation. Approaches that used highly accurate long reads and parent-child data with graph-based haplotype phasing during assembly outperformed those that did not. Developing a combination of the top-performing methods, we generated our first high-quality diploid reference assembly, containing only approximately four gaps per chromosome on average, with most chromosomes within ±1% of the length of CHM13. Nearly 48% of protein-coding genes have non-synonymous amino acid changes between haplotypes, and centromeric regions showed the highest diversity. Our findings serve as a foundation for assembling near-complete diploid human genomes at scale for a pangenome reference to capture global genetic variation from single nucleotides to structural rearrangements.
Published: 2022

4. Pan-conserved segment tags identify ultra-conserved sequences across assemblies in the human pangenome

Author: Liao, Wen-Wei, Asri, Mobin, Ebler, Jana, Doerr, Daniel, Haukness, Marina, Hickey, Glenn, Lu, Shuangjia, Lucas, Julian K., Monlong, Jean, Abel, Haley J., Buonaiuto, Silvia, Chang, Xian H., Cheng, Haoyu, Chu, Justin, Colonna, Vincenza, Eizenga, Jordan M., Feng, Xiaowen, Fischer, Christian, Fulton, Robert S., Garg, Shilpa, Groza, Cristian, Guarracino, Andrea, Harvey, William T., Heumos, Simon, Howe, Kerstin, Jain, Miten, Lu, Tsung-Yu, Markello, Charles, Martin, Fergal J., Mitchell, Matthew W., Munson, Katherine M., Mwaniki, Moses Njagi, Novak, Adam M., Olsen, Hugh E., Pesout, Trevor, Porubsky, David, Prins, Pjotr, Sibbesen, Jonas A., Tomlinson, Chad, Villani, Flavia, Vollger, Mitchell R., Antonacci-Fulton, Lucinda L., Baid, Gunjan, Baker, Carl A., Belyaeva, Anastasiya, Billis, Konstantinos, Carroll, Andrew, Chang, Pi-Chuan, Cody, Sarah, Cook, Daniel E., Cornejo, Omar E., Diekhans, Mark, Ebert, Peter, Fairley, Susan, Fedrigo, Olivier, Felsenfeld, Adam L., Formenti, Giulio, Frankish, Adam, Gao, Yan, Giron, Carlos Garcia, Green, Richard E., Haggerty, Leanne, Hoekzema, Kendra, Hourlier, Thibaut, Ji, Hanlee P., Kolesnikov, Alexey, Korbel, Jan O., Kordosky, Jennifer, Lee, HoJoon, Lewis, Alexandra P., Magalhães, Hugo, Marco-Sola, Santiago, Marijon, Pierre, McDaniel, Jennifer, Mountcastle, Jacquelyn, Nattestad, Maria, Olson, Nathan D., Puiu, Daniela, Regier, Allison A., Rhie, Arang, Sacco, Samuel, Sanders, Ashley D., Schneider, Valerie A., Schultz, Baergen I., Shafin, Kishwar, Sirén, Jouni, Smith, Michael W., Sofia, Heidi J., Abou Tayoun, Ahmad N., Thibaud-Nissen, Françoise, Tricomi, Francesca Floriana, Wagner, Justin, Wood, Jonathan M.D., Zimin, Aleksey V., Popejoy, Alice B., Bourque, Guillaume, Chaisson, Mark J.P., Flicek, Paul, Phillippy, Adam M., Zook, Justin M., Eichler, Evan E., Haussler, David, Jarvis, Erich D., Miga, Karen H., Wang, Ting, Garrison, Erik, Marschall, Tobias, Hall, Ira, Li, Heng, Paten, Benedict, Greer, Stephanie U., Pavlichin, Dmitri S., Zhou, Bo, Urban, Alexander E., and Weissman, Tsachy
Published: 2023
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5. 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

6. Re-sequencing expands our understanding of the phenotypic impact of variants at GWAS loci.

Author: Service, Susan K, Teslovich, Tanya M, Fuchsberger, Christian, Ramensky, Vasily, Yajnik, Pranav, Koboldt, Daniel C, Larson, David E, Zhang, Qunyuan, Lin, Ling, Welch, Ryan, Ding, Li, McLellan, Michael D, O'Laughlin, Michele, Fronick, Catrina, Fulton, Lucinda L, Magrini, Vincent, Swift, Amy, Elliott, Paul, Jarvelin, Marjo-Riitta, Kaakinen, Marika, McCarthy, Mark I, Peltonen, Leena, Pouta, Anneli, Bonnycastle, Lori L, Collins, Francis S, Narisu, Narisu, Stringham, Heather M, Tuomilehto, Jaakko, Ripatti, Samuli, Fulton, Robert S, Sabatti, Chiara, Wilson, Richard K, Boehnke, Michael, and Freimer, Nelson B
Subjects: Humans, Cholesterol, Genotype, Linkage Disequilibrium, Phenotype, Quantitative Trait Loci, Population Groups, European Continental Ancestry Group, Finland, Cholesterol, HDL, Genome-Wide Association Study, High-Throughput Nucleotide Sequencing, HDL, Genetics, Developmental Biology
Abstract: Genome-wide association studies (GWAS) have identified >500 common variants associated with quantitative metabolic traits, but in aggregate such variants explain at most 20-30% of the heritable component of population variation in these traits. To further investigate the impact of genotypic variation on metabolic traits, we conducted re-sequencing studies in >6,000 members of a Finnish population cohort (The Northern Finland Birth Cohort of 1966 [NFBC]) and a type 2 diabetes case-control sample (The Finland-United States Investigation of NIDDM Genetics [FUSION] study). By sequencing the coding sequence and 5' and 3' untranslated regions of 78 genes at 17 GWAS loci associated with one or more of six metabolic traits (serum levels of fasting HDL-C, LDL-C, total cholesterol, triglycerides, plasma glucose, and insulin), and conducting both single-variant and gene-level association tests, we obtained a more complete understanding of phenotype-genotype associations at eight of these loci. At all eight of these loci, the identification of new associations provides significant evidence for multiple genetic signals to one or more phenotypes, and at two loci, in the genes ABCA1 and CETP, we found significant gene-level evidence of association to non-synonymous variants with MAF
Published: 2014

7. Pangenome graph construction from genome alignments with Minigraph-Cactus.

Author: Hickey, Glenn, Monlong, Jean, Ebler, Jana, Novak, Adam M., Eizenga, Jordan M., Gao, Yan, Abel, Haley J., Antonacci-Fulton, Lucinda L., Asri, Mobin, Baid, Gunjan, Baker, Carl A., Belyaeva, Anastasiya, Billis, Konstantinos, Bourque, Guillaume, Buonaiuto, Silvia, Carroll, Andrew, Chaisson, Mark J. P., Chang, Pi-Chuan, Chang, Xian H., and Cheng, Haoyu
Abstract: Pangenome references address biases of reference genomes by storing a representative set of diverse haplotypes and their alignment, usually as a graph. Alternate alleles determined by variant callers can be used to construct pangenome graphs, but advances in long-read sequencing are leading to widely available, high-quality phased assemblies. Constructing a pangenome graph directly from assemblies, as opposed to variant calls, leverages the graph's ability to represent variation at different scales. Here we present the Minigraph-Cactus pangenome pipeline, which creates pangenomes directly from whole-genome alignments, and demonstrate its ability to scale to 90 human haplotypes from the Human Pangenome Reference Consortium. The method builds graphs containing all forms of genetic variation while allowing use of current mapping and genotyping tools. We measure the effect of the quality and completeness of reference genomes used for analysis within the pangenomes and show that using the CHM13 reference from the Telomere-to-Telomere Consortium improves the accuracy of our methods. We also demonstrate construction of a Drosophila melanogaster pangenome. Constructing genome graphs directly from genome assemblies overcomes single-reference bias. [ABSTRACT FROM AUTHOR]
Published: 2024
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8. Pan-conserved segment tags identify ultra-conserved sequences across assemblies in the human pangenome

Author: Lee, HoJoon, primary, Greer, Stephanie U., additional, Pavlichin, Dmitri S., additional, Zhou, Bo, additional, Urban, Alexander E., additional, Weissman, Tsachy, additional, Ji, Hanlee P., additional, Liao, Wen-Wei, additional, Asri, Mobin, additional, Ebler, Jana, additional, Doerr, Daniel, additional, Haukness, Marina, additional, Hickey, Glenn, additional, Lu, Shuangjia, additional, Lucas, Julian K., additional, Monlong, Jean, additional, Abel, Haley J., additional, Buonaiuto, Silvia, additional, Chang, Xian H., additional, Cheng, Haoyu, additional, Chu, Justin, additional, Colonna, Vincenza, additional, Eizenga, Jordan M., additional, Feng, Xiaowen, additional, Fischer, Christian, additional, Fulton, Robert S., additional, Garg, Shilpa, additional, Groza, Cristian, additional, Guarracino, Andrea, additional, Harvey, William T., additional, Heumos, Simon, additional, Howe, Kerstin, additional, Jain, Miten, additional, Lu, Tsung-Yu, additional, Markello, Charles, additional, Martin, Fergal J., additional, Mitchell, Matthew W., additional, Munson, Katherine M., additional, Mwaniki, Moses Njagi, additional, Novak, Adam M., additional, Olsen, Hugh E., additional, Pesout, Trevor, additional, Porubsky, David, additional, Prins, Pjotr, additional, Sibbesen, Jonas A., additional, Tomlinson, Chad, additional, Villani, Flavia, additional, Vollger, Mitchell R., additional, Antonacci-Fulton, Lucinda L., additional, Baid, Gunjan, additional, Baker, Carl A., additional, Belyaeva, Anastasiya, additional, Billis, Konstantinos, additional, Carroll, Andrew, additional, Chang, Pi-Chuan, additional, Cody, Sarah, additional, Cook, Daniel E., additional, Cornejo, Omar E., additional, Diekhans, Mark, additional, Ebert, Peter, additional, Fairley, Susan, additional, Fedrigo, Olivier, additional, Felsenfeld, Adam L., additional, Formenti, Giulio, additional, Frankish, Adam, additional, Gao, Yan, additional, Giron, Carlos Garcia, additional, Green, Richard E., additional, Haggerty, Leanne, additional, Hoekzema, Kendra, additional, Hourlier, Thibaut, additional, Kolesnikov, Alexey, additional, Korbel, Jan O., additional, Kordosky, Jennifer, additional, Lee, HoJoon, additional, Lewis, Alexandra P., additional, Magalhães, Hugo, additional, Marco-Sola, Santiago, additional, Marijon, Pierre, additional, McDaniel, Jennifer, additional, Mountcastle, Jacquelyn, additional, Nattestad, Maria, additional, Olson, Nathan D., additional, Puiu, Daniela, additional, Regier, Allison A., additional, Rhie, Arang, additional, Sacco, Samuel, additional, Sanders, Ashley D., additional, Schneider, Valerie A., additional, Schultz, Baergen I., additional, Shafin, Kishwar, additional, Sirén, Jouni, additional, Smith, Michael W., additional, Sofia, Heidi J., additional, Abou Tayoun, Ahmad N., additional, Thibaud-Nissen, Françoise, additional, Tricomi, Francesca Floriana, additional, Wagner, Justin, additional, Wood, Jonathan M.D., additional, Zimin, Aleksey V., additional, Popejoy, Alice B., additional, Bourque, Guillaume, additional, Chaisson, Mark J.P., additional, Flicek, Paul, additional, Phillippy, Adam M., additional, Zook, Justin M., additional, Eichler, Evan E., additional, Haussler, David, additional, Jarvis, Erich D., additional, Miga, Karen H., additional, Wang, Ting, additional, Garrison, Erik, additional, Marschall, Tobias, additional, Hall, Ira, additional, Li, Heng, additional, and Paten, Benedict, additional
Published: 2023
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9. Whole-genome analysis informs breast cancer response to aromatase inhibition

Author: Ellis, Matthew J, Ding, Li, Shen, Dong, Luo, Jingqin, Suman, Vera J, Wallis, John W, Van Tine, Brian A, Hoog, Jeremy, Goiffon, Reece J, Goldstein, Theodore C, Ng, Sam, Lin, Li, Crowder, Robert, Snider, Jacqueline, Ballman, Karla, Weber, Jason, Chen, Ken, Koboldt, Daniel C, Kandoth, Cyriac, Schierding, William S, McMichael, Joshua F, Miller, Christopher A, Lu, Charles, Harris, Christopher C, McLellan, Michael D, Wendl, Michael C, DeSchryver, Katherine, Allred, D Craig, Esserman, Laura, Unzeitig, Gary, Margenthaler, Julie, Babiera, GV, Marcom, P Kelly, Guenther, JM, Leitch, Marilyn, Hunt, Kelly, Olson, John, Tao, Yu, Maher, Christopher A, Fulton, Lucinda L, Fulton, Robert S, Harrison, Michelle, Oberkfell, Ben, Du, Feiyu, Demeter, Ryan, Vickery, Tammi L, Elhammali, Adnan, Piwnica-Worms, Helen, McDonald, Sandra, Watson, Mark, Dooling, David J, Ota, David, Chang, Li-Wei, Bose, Ron, Ley, Timothy J, Piwnica-Worms, David, Stuart, Joshua M, Wilson, Richard K, and Mardis, Elaine R
Subjects: Biological Sciences, Biomedical and Clinical Sciences, Genetics, Clinical Sciences, Oncology and Carcinogenesis, Cancer, Breast Cancer, Human Genome, Biotechnology, Anastrozole, Androstadienes, Antineoplastic Agents, Aromatase, Aromatase Inhibitors, Breast Neoplasms, DNA Repair, Exome, Exons, Female, Genetic Variation, Genome, Human, Humans, Letrozole, MAP Kinase Kinase 4, MAP Kinase Kinase Kinase 1, Mutation, Nitriles, Receptors, Estrogen, Treatment Outcome, Triazoles, General Science & Technology
Abstract: To correlate the variable clinical features of oestrogen-receptor-positive breast cancer with somatic alterations, we studied pretreatment tumour biopsies accrued from patients in two studies of neoadjuvant aromatase inhibitor therapy by massively parallel sequencing and analysis. Eighteen significantly mutated genes were identified, including five genes (RUNX1, CBFB, MYH9, MLL3 and SF3B1) previously linked to haematopoietic disorders. Mutant MAP3K1 was associated with luminal A status, low-grade histology and low proliferation rates, whereas mutant TP53 was associated with the opposite pattern. Moreover, mutant GATA3 correlated with suppression of proliferation upon aromatase inhibitor treatment. Pathway analysis demonstrated that mutations in MAP2K4, a MAP3K1 substrate, produced similar perturbations as MAP3K1 loss. Distinct phenotypes in oestrogen-receptor-positive breast cancer are associated with specific patterns of somatic mutations that map into cellular pathways linked to tumour biology, but most recurrent mutations are relatively infrequent. Prospective clinical trials based on these findings will require comprehensive genome sequencing.
Published: 2012

10. A novel retinoblastoma therapy from genomic and epigenetic analyses.

Author: Zhang, Jinghui, Benavente, Claudia A, McEvoy, Justina, Flores-Otero, Jacqueline, Ding, Li, Chen, Xiang, Ulyanov, Anatoly, Wu, Gang, Wilson, Matthew, Wang, Jianmin, Brennan, Rachel, Rusch, Michael, Manning, Amity L, Ma, Jing, Easton, John, Shurtleff, Sheila, Mullighan, Charles, Pounds, Stanley, Mukatira, Suraj, Gupta, Pankaj, Neale, Geoff, Zhao, David, Lu, Charles, Fulton, Robert S, Fulton, Lucinda L, Hong, Xin, Dooling, David J, Ochoa, Kerri, Naeve, Clayton, Dyson, Nicholas J, Mardis, Elaine R, Bahrami, Armita, Ellison, David, Wilson, Richard K, Downing, James R, and Dyer, Michael A
Subjects: Cell Line, Animals, Humans, Mice, Retinoblastoma, Aneuploidy, Chromosomal Instability, Intracellular Signaling Peptides and Proteins, Retinoblastoma Protein, Protein Kinase Inhibitors, Xenograft Model Antitumor Assays, Sequence Analysis, DNA, Genomics, Cell Death, Cell Survival, Epigenesis, Genetic, Gene Expression Regulation, Neoplastic, Mutation, Genes, Retinoblastoma, Protein-Tyrosine Kinases, Molecular Targeted Therapy, Syk Kinase, Epigenesis, Genetic, Gene Expression Regulation, Neoplastic, Genes, Sequence Analysis, DNA, General Science & Technology
Abstract: Retinoblastoma is an aggressive childhood cancer of the developing retina that is initiated by the biallelic loss of RB1. Tumours progress very quickly following RB1 inactivation but the underlying mechanism is not known. Here we show that the retinoblastoma genome is stable, but that multiple cancer pathways can be epigenetically deregulated. To identify the mutations that cooperate with RB1 loss, we performed whole-genome sequencing of retinoblastomas. The overall mutational rate was very low; RB1 was the only known cancer gene mutated. We then evaluated the role of RB1 in genome stability and considered non-genetic mechanisms of cancer pathway deregulation. For example, the proto-oncogene SYK is upregulated in retinoblastoma and is required for tumour cell survival. Targeting SYK with a small-molecule inhibitor induced retinoblastoma tumour cell death in vitro and in vivo. Thus, retinoblastomas may develop quickly as a result of the epigenetic deregulation of key cancer pathways as a direct or indirect result of RB1 loss.
Published: 2012

11. A draft human pangenome reference

Author: Liao, Wen Wei, Asri, Mobin, Ebler, Jana, Doerr, Daniel, Haukness, Marina, Hickey, Glenn, Lu, Shuangjia, Lucas, Julian K., Monlong, Jean, Abel, Haley J., Buonaiuto, Silvia, Chang, Xian H., Cheng, Haoyu, Chu, Justin, Colonna, Vincenza, Eizenga, Jordan M., Feng, Xiaowen, Fischer, Christian, Fulton, Robert S., Garg, Shilpa, Groza, Cristian, Guarracino, Andrea, Harvey, William T., Heumos, Simon, Howe, Kerstin, Jain, Miten, Lu, Tsung Yu, Markello, Charles, Martin, Fergal J., Mitchell, Matthew W., Munson, Katherine M., Mwaniki, Moses Njagi, Novak, Adam M., Olsen, Hugh E., Pesout, Trevor, Porubsky, David, Prins, Pjotr, Sibbesen, Jonas A., Sirén, Jouni, Tomlinson, Chad, Villani, Flavia, Vollger, Mitchell R., Antonacci-Fulton, Lucinda L., Baid, Gunjan, Baker, Carl A., Belyaeva, Anastasiya, Billis, Konstantinos, Carroll, Andrew, Chang, Pi Chuan, Cody, Sarah, Cook, Daniel E., Cook-Deegan, Robert M., Cornejo, Omar E., Diekhans, Mark, Ebert, Peter, Fairley, Susan, Fedrigo, Olivier, Felsenfeld, Adam L., Formenti, Giulio, Frankish, Adam, Gao, Yan, Garrison, Nanibaa’ A., Giron, Carlos Garcia, Green, Richard E., Haggerty, Leanne, Hoekzema, Kendra, Hourlier, Thibaut, Ji, Hanlee P., Kenny, Eimear E., Koenig, Barbara A., Kolesnikov, Alexey, Korbel, Jan O., Kordosky, Jennifer, Koren, Sergey, Lee, Ho Joon, Lewis, Alexandra P., Magalhães, Hugo, Marco-Sola, Santiago, Marijon, Pierre, McCartney, Ann, McDaniel, Jennifer, Mountcastle, Jacquelyn, Nattestad, Maria, Nurk, Sergey, Olson, Nathan D., Popejoy, Alice B., Puiu, Daniela, Rautiainen, Mikko, Regier, Allison A., Rhie, Arang, Sacco, Samuel, Sanders, Ashley D., Schneider, Valerie A., Schultz, Baergen I., Shafin, Kishwar, Smith, Michael W., Sofia, Heidi J., Abou Tayoun, Ahmad N., Thibaud-Nissen, Françoise, Tricomi, Francesca Floriana, Wagner, Justin, Walenz, Brian, Wood, Jonathan M.D., Zimin, Aleksey V., Bourque, Guillaume, Chaisson, Mark J.P., Flicek, Paul, Phillippy, Adam M., Zook, Justin M., Eichler, Evan E., Haussler, David, Wang, Ting, Jarvis, Erich D., Miga, Karen H., Garrison, Erik, Marschall, Tobias, Hall, Ira M., Li, Heng, Paten, Benedict, Liao, Wen Wei, Asri, Mobin, Ebler, Jana, Doerr, Daniel, Haukness, Marina, Hickey, Glenn, Lu, Shuangjia, Lucas, Julian K., Monlong, Jean, Abel, Haley J., Buonaiuto, Silvia, Chang, Xian H., Cheng, Haoyu, Chu, Justin, Colonna, Vincenza, Eizenga, Jordan M., Feng, Xiaowen, Fischer, Christian, Fulton, Robert S., Garg, Shilpa, Groza, Cristian, Guarracino, Andrea, Harvey, William T., Heumos, Simon, Howe, Kerstin, Jain, Miten, Lu, Tsung Yu, Markello, Charles, Martin, Fergal J., Mitchell, Matthew W., Munson, Katherine M., Mwaniki, Moses Njagi, Novak, Adam M., Olsen, Hugh E., Pesout, Trevor, Porubsky, David, Prins, Pjotr, Sibbesen, Jonas A., Sirén, Jouni, Tomlinson, Chad, Villani, Flavia, Vollger, Mitchell R., Antonacci-Fulton, Lucinda L., Baid, Gunjan, Baker, Carl A., Belyaeva, Anastasiya, Billis, Konstantinos, Carroll, Andrew, Chang, Pi Chuan, Cody, Sarah, Cook, Daniel E., Cook-Deegan, Robert M., Cornejo, Omar E., Diekhans, Mark, Ebert, Peter, Fairley, Susan, Fedrigo, Olivier, Felsenfeld, Adam L., Formenti, Giulio, Frankish, Adam, Gao, Yan, Garrison, Nanibaa’ A., Giron, Carlos Garcia, Green, Richard E., Haggerty, Leanne, Hoekzema, Kendra, Hourlier, Thibaut, Ji, Hanlee P., Kenny, Eimear E., Koenig, Barbara A., Kolesnikov, Alexey, Korbel, Jan O., Kordosky, Jennifer, Koren, Sergey, Lee, Ho Joon, Lewis, Alexandra P., Magalhães, Hugo, Marco-Sola, Santiago, Marijon, Pierre, McCartney, Ann, McDaniel, Jennifer, Mountcastle, Jacquelyn, Nattestad, Maria, Nurk, Sergey, Olson, Nathan D., Popejoy, Alice B., Puiu, Daniela, Rautiainen, Mikko, Regier, Allison A., Rhie, Arang, Sacco, Samuel, Sanders, Ashley D., Schneider, Valerie A., Schultz, Baergen I., Shafin, Kishwar, Smith, Michael W., Sofia, Heidi J., Abou Tayoun, Ahmad N., Thibaud-Nissen, Françoise, Tricomi, Francesca Floriana, Wagner, Justin, Walenz, Brian, Wood, Jonathan M.D., Zimin, Aleksey V., Bourque, Guillaume, Chaisson, Mark J.P., Flicek, Paul, Phillippy, Adam M., Zook, Justin M., Eichler, Evan E., Haussler, David, Wang, Ting, Jarvis, Erich D., Miga, Karen H., Garrison, Erik, Marschall, Tobias, Hall, Ira M., Li, Heng, and Paten, Benedict
Abstract: Here the Human Pangenome Reference Consortium presents a first draft of the human pangenome reference. The pangenome contains 47 phased, diploid assemblies from a cohort of genetically diverse individuals 1. These assemblies cover more than 99% of the expected sequence in each genome and are more than 99% accurate at the structural and base pair levels. Based on alignments of the assemblies, we generate a draft pangenome that captures known variants and haplotypes and reveals new alleles at structurally complex loci. We also add 119 million base pairs of euchromatic polymorphic sequences and 1,115 gene duplications relative to the existing reference GRCh38. Roughly 90 million of the additional base pairs are derived from structural variation. Using our draft pangenome to analyse short-read data reduced small variant discovery errors by 34% and increased the number of structural variants detected per haplotype by 104% compared with GRCh38-based workflows, which enabled the typing of the vast majority of structural variant alleles per sample.
Published: 2023

12. Recombination between heterologous human acrocentric chromosomes.

Author: Guarracino, Andrea, Buonaiuto, Silvia, de Lima, Leonardo Gomes, Potapova, Tamara, Rhie, Arang, Koren, Sergey, Rubinstein, Boris, Fischer, Christian, Abel, Haley J., Antonacci-Fulton, Lucinda L., Asri, Mobin, Baid, Gunjan, Baker, Carl A., Belyaeva, Anastasiya, Billis, Konstantinos, Bourque, Guillaume, Carroll, Andrew, Chaisson, Mark J. P., Chang, Pi-Chuan, and Chang, Xian H.
Abstract: The short arms of the human acrocentric chromosomes 13, 14, 15, 21 and 22 (SAACs) share large homologous regions, including ribosomal DNA repeats and extended segmental duplications1,2. Although the resolution of these regions in the first complete assembly of a human genome—the Telomere-to-Telomere Consortium’s CHM13 assembly (T2T-CHM13)—provided a model of their homology3, it remained unclear whether these patterns were ancestral or maintained by ongoing recombination exchange. Here we show that acrocentric chromosomes contain pseudo-homologous regions (PHRs) indicative of recombination between non-homologous sequences. Utilizing an all-to-all comparison of the human pangenome from the Human Pangenome Reference Consortium4 (HPRC), we find that contigs from all of the SAACs form a community. A variation graph5 constructed from centromere-spanning acrocentric contigs indicates the presence of regions in which most contigs appear nearly identical between heterologous acrocentric chromosomes in T2T-CHM13. Except on chromosome 15, we observe faster decay of linkage disequilibrium in the pseudo-homologous regions than in the corresponding short and long arms, indicating higher rates of recombination6,7. The pseudo-homologous regions include sequences that have previously been shown to lie at the breakpoint of Robertsonian translocations8, and their arrangement is compatible with crossover in inverted duplications on chromosomes 13, 14 and 21. The ubiquity of signals of recombination between heterologous acrocentric chromosomes seen in the HPRC draft pangenome suggests that these shared sequences form the basis for recurrent Robertsonian translocations, providing sequence and population-based confirmation of hypotheses first developed from cytogenetic studies 50 years ago9.Comparisons within the human pangenome establish that homologous regions on short arms of heterologous human acrocentric chromosomes actively recombine, leading to the high rate of Robertsonian translocation breakpoints in these regions. [ABSTRACT FROM AUTHOR]
Published: 2023
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13. Increased mutation and gene conversion within human segmental duplications.

Author: Vollger, Mitchell R., Dishuck, Philip C., Harvey, William T., DeWitt, William S., Guitart, Xavi, Goldberg, Michael E., Rozanski, Allison N., Lucas, Julian, Asri, Mobin, Abel, Haley J., Antonacci-Fulton, Lucinda L., Baid, Gunjan, Baker, Carl A., Belyaeva, Anastasiya, Billis, Konstantinos, Bourque, Guillaume, Buonaiuto, Silvia, Carroll, Andrew, Chaisson, Mark J. P., and Chang, Pi-Chuan
Abstract: Single-nucleotide variants (SNVs) in segmental duplications (SDs) have not been systematically assessed because of the limitations of mapping short-read sequencing data1,2. Here we constructed 1:1 unambiguous alignments spanning high-identity SDs across 102 human haplotypes and compared the pattern of SNVs between unique and duplicated regions3,4. We find that human SNVs are elevated 60% in SDs compared to unique regions and estimate that at least 23% of this increase is due to interlocus gene conversion (IGC) with up to 4.3 megabase pairs of SD sequence converted on average per human haplotype. We develop a genome-wide map of IGC donors and acceptors, including 498 acceptor and 454 donor hotspots affecting the exons of about 800 protein-coding genes. These include 171 genes that have ‘relocated’ on average 1.61 megabase pairs in a subset of human haplotypes. Using a coalescent framework, we show that SD regions are slightly evolutionarily older when compared to unique sequences, probably owing to IGC. SNVs in SDs, however, show a distinct mutational spectrum: a 27.1% increase in transversions that convert cytosine to guanine or the reverse across all triplet contexts and a 7.6% reduction in the frequency of CpG-associated mutations when compared to unique DNA. We reason that these distinct mutational properties help to maintain an overall higher GC content of SD DNA compared to that of unique DNA, probably driven by GC-biased conversion between paralogous sequences5,6.A study comparing the pattern of single-nucleotide variation between unique and duplicated regions of the human genome shows that mutation rate and interlocus gene conversion are elevated in duplicated regions. [ABSTRACT FROM AUTHOR]
Published: 2023
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14. Semi-automated assembly of high-quality diploid human reference genomes

Author: Jarvis, Erich D., Formenti, Giulio, Rhie, Arang, Guarracino, Andrea, Yang, Chentao, Wood, Jonathan, Tracey, Alan, Thibaud-Nissen, Francoise, Vollger, Mitchell R., Porubsky, David, Cheng, Haoyu, Asri, Mobin, Logsdon, Glennis A., Carnevali, Paolo, Chaisson, Mark J.P., Chin, Chen Shan, Cody, Sarah, Collins, Joanna, Ebert, Peter, Escalona, Merly, Fedrigo, Olivier, Fulton, Robert S., Fulton, Lucinda L., Garg, Shilpa, Gerton, Jennifer L., Ghurye, Jay, Granat, Anastasiya, Green, Richard E., Harvey, William, Hasenfeld, Patrick, Hastie, Alex, Haukness, Marina, Jaeger, Erich B., Jain, Miten, Kirsche, Melanie, Kolmogorov, Mikhail, Korbel, Jan O., Koren, Sergey, Korlach, Jonas, Lee, Joyce, Li, Daofeng, Lindsay, Tina, Lucas, Julian, Luo, Feng, Marschall, Tobias, Mitchell, Matthew W., McDaniel, Jennifer, Nie, Fan, Zhang, Guojie, Li, Heng, Jarvis, Erich D., Formenti, Giulio, Rhie, Arang, Guarracino, Andrea, Yang, Chentao, Wood, Jonathan, Tracey, Alan, Thibaud-Nissen, Francoise, Vollger, Mitchell R., Porubsky, David, Cheng, Haoyu, Asri, Mobin, Logsdon, Glennis A., Carnevali, Paolo, Chaisson, Mark J.P., Chin, Chen Shan, Cody, Sarah, Collins, Joanna, Ebert, Peter, Escalona, Merly, Fedrigo, Olivier, Fulton, Robert S., Fulton, Lucinda L., Garg, Shilpa, Gerton, Jennifer L., Ghurye, Jay, Granat, Anastasiya, Green, Richard E., Harvey, William, Hasenfeld, Patrick, Hastie, Alex, Haukness, Marina, Jaeger, Erich B., Jain, Miten, Kirsche, Melanie, Kolmogorov, Mikhail, Korbel, Jan O., Koren, Sergey, Korlach, Jonas, Lee, Joyce, Li, Daofeng, Lindsay, Tina, Lucas, Julian, Luo, Feng, Marschall, Tobias, Mitchell, Matthew W., McDaniel, Jennifer, Nie, Fan, Zhang, Guojie, and Li, Heng
Abstract: The current human reference genome, GRCh38, represents over 20 years of effort to generate a high-quality assembly, which has benefitted society1,2. However, it still has many gaps and errors, and does not represent a biological genome as it is a blend of multiple individuals3,4. Recently, a high-quality telomere-to-telomere reference, CHM13, was generated with the latest long-read technologies, but it was derived from a hydatidiform mole cell line with a nearly homozygous genome5. To address these limitations, the Human Pangenome Reference Consortium formed with the goal of creating high-quality, cost-effective, diploid genome assemblies for a pangenome reference that represents human genetic diversity6. Here, in our first scientific report, we determined which combination of current genome sequencing and assembly approaches yield the most complete and accurate diploid genome assembly with minimal manual curation. Approaches that used highly accurate long reads and parent–child data with graph-based haplotype phasing during assembly outperformed those that did not. Developing a combination of the top-performing methods, we generated our first high-quality diploid reference assembly, containing only approximately four gaps per chromosome on average, with most chromosomes within ±1% of the length of CHM13. Nearly 48% of protein-coding genes have non-synonymous amino acid changes between haplotypes, and centromeric regions showed the highest diversity. Our findings serve as a foundation for assembling near-complete diploid human genomes at scale for a pangenome reference to capture global genetic variation from single nucleotides to structural rearrangements.
Published: 2022

15. Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing

Author: Ding, Li, Ley, Timothy J., Larson, David E., Miller, Christopher A., Koboldt, Daniel C., Welch, John S., Ritchey, Julie K., Young, Margaret A., Lamprecht, Tamara, McLellan, Michael D., McMichael, Joshua F., Wallis, John W., Lu, Charles, Shen, Dong, Harris, Christopher C., Dooling, David J., Fulton, Robert S., Fulton, Lucinda L., Chen, Ken, Schmidt, Heather, Kalicki-Veizer, Joelle, Magrini, Vincent J., Cook, Lisa, McGrath, Sean D., Vickery, Tammi L., Wendl, Michael C., Heath, Sharon, Watson, Mark A., Link, Daniel C., Tomasson, Michael H., Shannon, William D., Payton, Jacqueline E., Kulkarni, Shashikant, Westervelt, Peter, Walter, Matthew J., Graubert, Timothy A., Mardis, Elaine R., Wilson, Richard K., and DiPersio, John F.
Subjects: Nucleotide sequencing -- Health aspects, DNA sequencing -- Health aspects, Clonal selection theory -- Abnormalities, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract: Most patients with acute myeloid leukaemia (AML) die from progressive disease after relapse, which is associated with clonal evolution at the cytogenetic level (1,2). To determine the mutational spectrum associated with relapse, we sequenced the primary tumour and relapse genomes from eight AML patients, and validated hundreds of somatic mutations using deep sequencing; this allowed us to define clonality and clonal evolution patterns precisely at relapse. In addition to discovering novel, recurrently mutated genes (for example, WAC, SMC3, DIS3, DDX41 and DAXX) in AML, we also found two major clonal evolution patterns during AML relapse: (1) the founding clone in the primary tumour gained mutations and evolved into the relapse clone, or (2) a subclone of the founding clone survived initial therapy, gained additional mutations and expanded at relapse. In all cases, chemotherapy failed to eradicate the founding clone. The comparison of relapse-specific versus primary tumour mutations in all eight cases revealed an increase in transversions, probably due to DNA damage caused by cytotoxic chemotherapy. These data demonstrate that AML relapse is associated with the addition of new mutations and clonal evolution, which is shaped, in part, by the chemotherapy that the patients receive to establish and maintain remissions., To investigate the genetic changes associated with AML relapse, and to determine whether clonal evolution contributes to relapse, we performed whole-genome sequencing of primary tumour-relapse pairs and matched skin samples [...]
Published: 2012
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16. C11orf95–RELA fusions drive oncogenic NF-κB signalling in ependymoma

Author: Parker, Matthew, Mohankumar, Kumarasamypet M., Punchihewa, Chandanamali, Weinlich, Ricardo, Dalton, James D., Li, Yongjin, Lee, Ryan, Tatevossian, Ruth G., Phoenix, Timothy N., Thiruvenkatam, Radhika, White, Elsie, Tang, Bo, Orisme, Wilda, Gupta, Kirti, Rusch, Michael, Chen, Xiang, Li, Yuxin, Nagahawhatte, Panduka, Hedlund, Erin, Finkelstein, David, Wu, Gang, Shurtleff, Sheila, Easton, John, Boggs, Kristy, Yergeau, Donald, Vadodaria, Bhavin, Mulder, Heather L., Becksford, Jared, Gupta, Pankaj, Huether, Robert, Ma, Jing, Song, Guangchun, Gajjar, Amar, Merchant, Thomas, Boop, Frederick, Smith, Amy A., Ding, Li, Lu, Charles, Ochoa, Kerri, Zhao, David, Fulton, Robert S., Fulton, Lucinda L., Mardis, Elaine R., Wilson, Richard K., Downing, James R., Green, Douglas R., Zhang, Jinghui, Ellison, David W., and Gilbertson, Richard J.
Published: 2014
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17. The International HapMap Project

Author: Gibbs, Richard A., Belmont, John W., Hardenbol, Paul, Willis, Thomas D., Yu, Fuli, Yang, Huanming, Ch'ang, Lan-Yang, Huang, Wei, Liu, Bin, Shen, Yan, Tam, Paul Kwong-Hang, Tsui, Lap-Chee, Waye, Mary Miu Yee, Wong, Jeffrey Tze-Fei, Zeng, Changqing, Zhang, Qingrun, Chee, Mark S., Galver, Luana M., Kruglyak, Semyon, Murray, Sarah S., Oliphant, Arnold R., Montpetit, Alexandre, Hudson, Thomas J., Chagnon, Fanny, Ferretti, Vincent, Leboeuf, Martin, Phillips, Michael S., Verner, Andrei, Kwok, Pui-Yan, Duan, Shenghui, Lind, Denise L., Miller, Raymond D., Rice, John P., Saccone, Nancy L., Taillon-Miller, Patricia, Xiao, Ming, Nakamura, Yusuke, Sekine, Akihiro, Sorimachi, Koki, Tanaka, Toshihiro, Tanaka, Yoichi, Tsunoda, Tatsuhiko, Yoshino, Eiji, Bentley, David R., Deloukas, Panos, Hunt, Sarah, Powell, Don, Altshuler, David, Gabriel, Stacey B., Zhang, Houcan, Matsuda, Ichiro, Fukushima, Yoshimitsu, Macer, Darryl R., Suda, Eiko, Rotimi, Charles N., Adebamowo, Clement A., Aniagwu, Toyin, Marshall, Patricia A., Matthew, Olayemi, Nkwodimmah, Chibuzor, Royal, Charmaine D. M., Leppert, Mark F., Dixon, Missy, Stein, Lincoln D., Cunningham, Fiona, Kanani, Ardavan, Thorisson, Gudmundur A., Chakravarti, Aravinda, Chen, Peter E., Cutler, David J., Kashuk, Carl S., Donnelly, Peter, Marchini, Jonathan, McVean, Gilean A. T., Myers, Simon R., Cardon, Lon R., Abecasis, Goncalo R., Morris, Andrew, Weir, Bruce S., Mullikin, James C., Sherry, Stephen T., Feolo, Michael, Daly, Mark J., Schaffner, Stephen F., Qiu, Renzong, Kent, Alastair, Dunston, Georgia M., Kato, Kazuto, Niikawa, Norio, Knoppers, Bartha M., Foster, Morris W., Clayton, Ellen Wright, Wang, Vivian Ota, Watkin, Jessica, Sodergren, Erica, Weinstock, George M., Wilson, Richard K., Fulton, Lucinda L., Rogers, Jane, Birren, Bruce W., Han, Hua, Wang, Hongguang, Godbout, Martin, Wallenburg, John C., L'Archeveque, Paul, Bellemare, Guy, Todani, Kazuo, Fujita, Takashi, Tanaka, Satoshi, Holden, Arthur L., Lai, Eric H., Collins, Francis S., Brooks, Lisa D., McEwen, Jean E., Guyer, Mark S., Jordan, Elke, Peterson, Jane L., Spiegel, Jack, Sung, Lawrence M., Zacharia, Lynn F., Kennedy, Karen, Dunn, Michael G., Seabrook, Richard, Shillito, Mark, Skene, Barbara, Stewart, John G., Cho, Mildred K., Duster, Troy, Jasperse, Marla, Licinio, Julio, Long, Jeffrey C., Ossorio, Pilar N., Spallone, Patricia, Terry, Sharon F., Boehnke, Michael, Douglas, Julie A., Hudson, Richard R., Kruglyak, Leonid, and Nussbaum, Robert L.
Subjects: Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract: Author(s): The International HapMap Consortium ; (Participants are arranged alphabetically by institution, and then by principal investigator and alphabetically by last name.); ; Genotyping centres: Baylor College of Medicine and [...]
Published: 2003
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18. 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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19. Novel mutations target distinct subgroups of medulloblastoma

Author: Robinson, Giles, Parker, Matthew, Kranenburg, Tanya A., Lu, Charles, Chen, Xiang, Ding, Li, Phoenix, Timothy N., Hedlund, Erin, Wei, Lei, Zhu, Xiaoyan, Chalhoub, Nader, Baker, Suzanne J., Huether, Robert, Kriwacki, Richard, Curley, Natasha, Thiruvenkatam, Radhika, Wang, Jianmin, Wu, Gang, Rusch, Michael, Hong, Xin, Becksfort, Jared, Gupta, Pankaj, Ma, Jing, Easton, John, Vadodaria, Bhavin, Onar-Thomas, Arzu, Lin, Tong, Li, Shaoyi, Pounds, Stanley, Paugh, Steven, Zhao, David, Kawauchi, Daisuke, Roussel, Martine F., Finkelstein, David, Ellison, David W., Lau, Ching C., Bouffet, Eric, Hassall, Tim, Gururangan, Sridharan, Cohn, Richard, Fulton, Robert S., Fulton, Lucinda L., Dooling, David J., Ochoa, Kerri, Gajjar, Amar, Mardis, Elaine R., Wilson, Richard K., Downing, James R., Zhang, Jinghui, and Gilbertson, Richard J.
Published: 2012
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20. A framework for human microbiome research

Author: Methé, Barbara A., Nelson, Karen E., Pop, Mihai, Creasy, Heather H., Giglio, Michelle G., Huttenhower, Curtis, Gevers, Dirk, Petrosino, Joseph F., Abubucker, Sahar, Badger, Jonathan H., Chinwalla, Asif T., Earl, Ashlee M., FitzGerald, Michael G., Fulton, Robert S., Hallsworth-Pepin, Kymberlie, Lobos, Elizabeth A., Madupu, Ramana, Magrini, Vincent, Martin, John C., Mitreva, Makedonka, Muzny, Donna M., Sodergren, Erica J., Versalovic, James, Wollam, Aye M., Worley, Kim C., Wortman, Jennifer R., Young, Sarah K., Zeng, Qiandong, Aagaard, Kjersti M., Abolude, Olukemi O., Allen-Vercoe, Emma, Alm, Eric J., Alvarado, Lucia, Andersen, Gary L., Anderson, Scott, Appelbaum, Elizabeth, Arachchi, Harindra M., Armitage, Gary, Arze, Cesar A., Ayvaz, Tulin, Baker, Carl C., Begg, Lisa, Belachew, Tsegahiwot, Bhonagiri, Veena, Bihan, Monika, Blaser, Martin J., Bloom, Toby, Bonazzi, Vivien R., Brooks, Paul, Buck, Gregory A., Buhay, Christian J., Busam, Dana A., Campbell, Joseph L., Canon, Shane R., Cantarel, Brandi L., Chain, Patrick S., Chen, I-Min A., Chen, Lei, Chhibba, Shaila, Chu, Ken, Ciulla, Dawn M., Clemente, Jose C., Clifton, Sandra W., Conlan, Sean, Crabtree, Jonathan, Cutting, Mary A., Davidovics, Noam J., Davis, Catherine C., DeSantis, Todd Z., Deal, Carolyn, Delehaunty, Kimberley D., Dewhirst, Floyd E., Deych, Elena, Ding, Yan, Dooling, David J., Dugan, Shannon P., Dunne, Michael W., Jr, Durkin, Scott A., Edgar, Robert C., Erlich, Rachel L., Farmer, Candace N., Farrell, Ruth M., Faust, Karoline, Feldgarden, Michael, Felix, Victor M., Fisher, Sheila, Fodor, Anthony A., Forney, Larry, Foster, Leslie, Di Francesco, Valentina, Friedman, Jonathan, Friedrich, Dennis C., Fronick, Catrina C., Fulton, Lucinda L., Gao, Hongyu, Garcia, Nathalia, Giannoukos, Georgia, Giblin, Christina, Giovanni, Maria Y., Goldberg, Jonathan M., Goll, Johannes, Gonzalez, Antonio, Griggs, Allison, Gujja, Sharvari, Haas, Brian J., Hamilton, Holli A., Harris, Emily L., Hepburn, Theresa A., Herter, Brandi, Hoffmann, Diane E., Holder, Michael E., Howarth, Clinton, Huang, Katherine H., Huse, Susan M., Izard, Jacques, Jansson, Janet K., Jiang, Huaiyang, Jordan, Catherine, Joshi, Vandita, Katancik, James A., Keitel, Wendy A., Kelley, Scott T., Kells, Cristyn, Kinder-Haake, Susan, King, Nicholas B., Knight, Rob, Knights, Dan, Kong, Heidi H., Koren, Omry, Koren, Sergey, Kota, Karthik C., Kovar, Christie L., Kyrpides, Nikos C., La Rosa, Patricio S., Lee, Sandra L., Lemon, Katherine P., Lennon, Niall, Lewis, Cecil M., Lewis, Lora, Ley, Ruth E., Li, Kelvin, Liolios, Konstantinos, Liu, Bo, Liu, Yue, Lo, Chien-Chi, Lozupone, Catherine A., Lunsford, Dwayne R., Madden, Tessa, Mahurkar, Anup A., Mannon, Peter J., Mardis, Elaine R., Markowitz, Victor M., Mavrommatis, Konstantinos, McCorrison, Jamison M., McDonald, Daniel, McEwen, Jean, McGuire, Amy L., McInnes, Pamela, Mehta, Teena, Mihindukulasuriya, Kathie A., Miller, Jason R., Minx, Patrick J., Newsham, Irene, Nusbaum, Chad, O’Laughlin, Michelle, Orvis, Joshua, Pagani, Ioanna, Palaniappan, Krishna, Patel, Shital M., Pearson, Matthew, Peterson, Jane, Podar, Mircea, Pohl, Craig, Pollard, Katherine S., Priest, Margaret E., Proctor, Lita M., Qin, Xiang, Raes, Jeroen, Ravel, Jacques, Reid, Jeffrey G., Rho, Mina, Rhodes, Rosamond, Riehle, Kevin P., Rivera, Maria C., Rodriguez-Mueller, Beltran, Rogers, Yu-Hui, Ross, Matthew C., Russ, Carsten, Sanka, Ravi K., Sankar, Pamela, Sathirapongsasuti, Fah J., Schloss, Jeffery A., Schloss, Patrick D., Schmidt, Thomas M., Scholz, Matthew, Schriml, Lynn, Schubert, Alyxandria M., Segata, Nicola, Segre, Julia A., Shannon, William D., Sharp, Richard R., Sharpton, Thomas J., Shenoy, Narmada, Sheth, Nihar U., Simone, Gina A., Singh, Indresh, Smillie, Chris S., Sobel, Jack D., Sommer, Daniel D., Spicer, Paul, Sutton, Granger G., Sykes, Sean M., Tabbaa, Diana G., Thiagarajan, Mathangi, Tomlinson, Chad M., Torralba, Manolito, Treangen, Todd J., Truty, Rebecca M., Vishnivetskaya, Tatiana A., Walker, Jason, Wang, Lu, Wang, Zhengyuan, Ward, Doyle V., Warren, Wesley, Watson, Mark A., Wellington, Christopher, Wetterstrand, Kris A., White, James R., Wilczek-Boney, Katarzyna, Wu, Yuan Qing, Wylie, Kristine M., Wylie, Todd, Yandava, Chandri, Ye, Liang, Ye, Yuzhen, Yooseph, Shibu, Youmans, Bonnie P., Zhang, Lan, Zhou, Yanjiao, Zhu, Yiming, Zoloth, Laurie, Zucker, Jeremy D., Birren, Bruce W., Gibbs, Richard A., Highlander, Sarah K., Weinstock, George M., Wilson, Richard K., and White, Owen
Published: 2012
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21. Structure, function and diversity of the healthy human microbiome

Author: Huttenhower, Curtis, Gevers, Dirk, Knight, Rob, Abubucker, Sahar, Badger, Jonathan H., Chinwalla, Asif T., Creasy, Heather H., Earl, Ashlee M., FitzGerald, Michael G., Fulton, Robert S., Giglio, Michelle G., Hallsworth-Pepin, Kymberlie, Lobos, Elizabeth A., Madupu, Ramana, Magrini, Vincent, Martin, John C., Mitreva, Makedonka, Muzny, Donna M., Sodergren, Erica J., Versalovic, James, Wollam, Aye M., Worley, Kim C., Wortman, Jennifer R., Young, Sarah K., Zeng, Qiandong, Aagaard, Kjersti M., Abolude, Olukemi O., Allen-Vercoe, Emma, Alm, Eric J., Alvarado, Lucia, Andersen, Gary L., Anderson, Scott, Appelbaum, Elizabeth, Arachchi, Harindra M., Armitage, Gary, Arze, Cesar A., Ayvaz, Tulin, Baker, Carl C., Begg, Lisa, Belachew, Tsegahiwot, Bhonagiri, Veena, Bihan, Monika, Blaser, Martin J., Bloom, Toby, Bonazzi, Vivien, Brooks, Paul J., Buck, Gregory A., Buhay, Christian J., Busam, Dana A., Campbell, Joseph L., Canon, Shane R., Cantarel, Brandi L., Chain, Patrick S. G., Chen, I-Min A., Chen, Lei, Chhibba, Shaila, Chu, Ken, Ciulla, Dawn M., Clemente, Jose C., Clifton, Sandra W., Conlan, Sean, Crabtree, Jonathan, Cutting, Mary A., Davidovics, Noam J., Davis, Catherine C., DeSantis, Todd Z., Deal, Carolyn, Delehaunty, Kimberley D., Dewhirst, Floyd E., Deych, Elena, Ding, Yan, Dooling, David J., Dugan, Shannon P., Dunne, Wm Michael, Durkin, Scott A., Edgar, Robert C., Erlich, Rachel L., Farmer, Candace N., Farrell, Ruth M., Faust, Karoline, Feldgarden, Michael, Felix, Victor M., Fisher, Sheila, Fodor, Anthony A., Forney, Larry J., Foster, Leslie, Di Francesco, Valentina, Friedman, Jonathan, Friedrich, Dennis C., Fronick, Catrina C., Fulton, Lucinda L., Gao, Hongyu, Garcia, Nathalia, Giannoukos, Georgia, Giblin, Christina, Giovanni, Maria Y., Goldberg, Jonathan M., Goll, Johannes, Gonzalez, Antonio, Griggs, Allison, Gujja, Sharvari, Haake, Susan Kinder, Haas, Brian J., Hamilton, Holli A., Harris, Emily L., Hepburn, Theresa A., Herter, Brandi, Hoffmann, Diane E., Holder, Michael E., Howarth, Clinton, Huang, Katherine H., Huse, Susan M., Izard, Jacques, Jansson, Janet K., Jiang, Huaiyang, Jordan, Catherine, Joshi, Vandita, Katancik, James A., Keitel, Wendy A., Kelley, Scott T., Kells, Cristyn, King, Nicholas B., Knights, Dan, Kong, Heidi H., Koren, Omry, Koren, Sergey, Kota, Karthik C., Kovar, Christie L., Kyrpides, Nikos C., La Rosa, Patricio S., Lee, Sandra L., Lemon, Katherine P., Lennon, Niall, Lewis, Cecil M., Lewis, Lora, Ley, Ruth E., Li, Kelvin, Liolios, Konstantinos, Liu, Bo, Liu, Yue, Lo, Chien-Chi, Lozupone, Catherine A., Lunsford, Dwayne R., Madden, Tessa, Mahurkar, Anup A., Mannon, Peter J., Mardis, Elaine R., Markowitz, Victor M., Mavromatis, Konstantinos, McCorrison, Jamison M., McDonald, Daniel, McEwen, Jean, McGuire, Amy L., McInnes, Pamela, Mehta, Teena, Mihindukulasuriya, Kathie A., Miller, Jason R., Minx, Patrick J., Newsham, Irene, Nusbaum, Chad, O’Laughlin, Michelle, Orvis, Joshua, Pagani, Ioanna, Palaniappan, Krishna, Patel, Shital M., Pearson, Matthew, Peterson, Jane, Podar, Mircea, Pohl, Craig, Pollard, Katherine S., Pop, Mihai, Priest, Margaret E., Proctor, Lita M., Qin, Xiang, Raes, Jeroen, Ravel, Jacques, Reid, Jeffrey G., Rho, Mina, Rhodes, Rosamond, Riehle, Kevin P., Rivera, Maria C., Rodriguez-Mueller, Beltran, Rogers, Yu-Hui, Ross, Matthew C., Russ, Carsten, Sanka, Ravi K., Sankar, Pamela, Sathirapongsasuti, Fah J., Schloss, Jeffery A., Schloss, Patrick D., Schmidt, Thomas M., Scholz, Matthew, Schriml, Lynn, Schubert, Alyxandria M., Segata, Nicola, Segre, Julia A., Shannon, William D., Sharp, Richard R., Sharpton, Thomas J., Shenoy, Narmada, Sheth, Nihar U., Simone, Gina A., Singh, Indresh, Smillie, Christopher S., Sobel, Jack D., Sommer, Daniel D., Spicer, Paul, Sutton, Granger G., Sykes, Sean M., Tabbaa, Diana G., Thiagarajan, Mathangi, Tomlinson, Chad M., Torralba, Manolito, Treangen, Todd J., Truty, Rebecca M., Vishnivetskaya, Tatiana A., Walker, Jason, Wang, Lu, Wang, Zhengyuan, Ward, Doyle V., Warren, Wesley, Watson, Mark A., Wellington, Christopher, Wetterstrand, Kris A., White, James R., Wilczek-Boney, Katarzyna, Wu, YuanQing, Wylie, Kristine M., Wylie, Todd, Yandava, Chandri, Ye, Liang, Ye, Yuzhen, Yooseph, Shibu, Youmans, Bonnie P., Zhang, Lan, Zhou, Yanjiao, Zhu, Yiming, Zoloth, Laurie, Zucker, Jeremy D., Birren, Bruce W., Gibbs, Richard A., Highlander, Sarah K., Methé, Barbara A., Nelson, Karen E., Petrosino, Joseph F., Weinstock, George M., Wilson, Richard K., and White, Owen
Published: 2012
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22. The genetic basis of early T-cell precursor acute lymphoblastic leukaemia

Author: Zhang, Jinghui, Ding, Li, Holmfeldt, Linda, Wu, Gang, Heatley, Sue L., Payne-Turner, Debbie, Easton, John, Chen, Xiang, Wang, Jianmin, Rusch, Michael, Lu, Charles, Chen, Shann-Ching, Wei, Lei, Collins-Underwood, Racquel J., Ma, Jing, Roberts, Kathryn G., Pounds, Stanley B., Ulyanov, Anatoly, Becksfort, Jared, Gupta, Pankaj, Huether, Robert, Kriwacki, Richard W., Parker, Matthew, McGoldrick, Daniel J., Zhao, David, Alford, Daniel, Espy, Stephen, Bobba, Kiran Chand, Song, Guangchun, Pei, Deqing, Cheng, Cheng, Roberts, Stefan, Barbato, Michael I., Campana, Dario, Coustan-Smith, Elaine, Shurtleff, Sheila A., Raimondi, Susana C., Kleppe, Maria, Cools, Jan, Shimano, Kristin A., Hermiston, Michelle L., Doulatov, Sergei, Eppert, Kolja, Laurenti, Elisa, Notta, Faiyaz, Dick, John E., Basso, Giuseppe, Hunger, Stephen P., Loh, Mignon L., Devidas, Meenakshi, Wood, Brent, Winter, Stuart, Dunsmore, Kimberley P., Fulton, Robert S., Fulton, Lucinda L., Hong, Xin, Harris, Christopher C., Dooling, David J., Ochoa, Kerri, Johnson, Kimberly J., Obenauer, John C., Evans, William E., Pui, Ching-Hon, Naeve, Clayton W., Ley, Timothy J., Mardis, Elaine R., Wilson, Richard K., Downing, James R., and Mullighan, Charles G.
Published: 2012
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23. Identification of a Novel TP53 Cancer Susceptibility Mutation Through Whole-Genome Sequencing of a Patient With Therapy-Related AML

Author: Link, Daniel C., Schuettpelz, Laura G., Shen, Dong, Wang, Jinling, Walter, Matthew J., Kulkarni, Shashikant, Payton, Jacqueline E., Ivanovich, Jennifer, Goodfellow, Paul J., Le Beau, Michelle, Koboldt, Daniel C., Dooling, David J., Fulton, Robert S., Bender, R. Hugh, Fulton, Lucinda L., Delehaunty, Kimberly D., Fronick, Catrina C., Appelbaum, Elizabeth L., Schmidt, Heather, Abbott, Rachel, O’Laughlin, Michelle, Chen, Ken, McLellan, Michael D., Varghese, Nobish, Nagarajan, Rakesh, Heath, Sharon, Graubert, Timothy A., Ding, Li, Ley, Timothy J., Zambetti, Gerard P., Wilson, Richard K., and Mardis, Elaine R.
Published: 2011
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24. Genome remodelling in a basal-like breast cancer metastasis and xenograft

Author: Ding, Li, Ellis, Matthew J., Li, Shunqiang, Larson, David E., Chen, Ken, Wallis, John W., Harris, Christopher C., McLellan, Michael D., Fulton, Robert S., Fulton, Lucinda L., Abbott, Rachel M., Hoog, Jeremy, Dooling, David J., Koboldt, Daniel C., Schmidt, Heather, Kalicki, Joelle, Zhang, Qunyuan, Chen, Lei, Lin, Ling, Wendl, Michael C., McMichael, Joshua F., Magrini, Vincent J., Cook, Lisa, McGrath, Sean D., Vickery, Tammi L., Appelbaum, Elizabeth, DeSchryver, Katherine, Davies, Sherri, Guintoli, Therese, Lin, Li, Crowder, Robert, Tao, Yu, Snider, Jacqueline E., Smith, Scott M., Dukes, Adam F., Sanderson, Gabriel E., Pohl, Craig S., Delehaunty, Kim D., Fronick, Catrina C., Pape, Kimberley A., Reed, Jerry S., Robinson, Jody S., Hodges, Jennifer S., Schierding, William, Dees, Nathan D., Shen, Dong, Locke, Devin P., Wiechert, Madeline E., Eldred, James M., Peck, Josh B., Oberkfell, Benjamin J., Lolofie, Justin T., Du, Feiyu, Hawkins, Amy E., OʼLaughlin, Michelle D., Bernard, Kelly E., Cunningham, Mark, Elliott, Glendoria, Mason, Mark D., Thompson, Dominic M., Jr, Ivanovich, Jennifer L., Goodfellow, Paul J., Perou, Charles M., Weinstock, George M., Aft, Rebecca, Watson, Mark, Ley, Timothy J., Wilson, Richard K., and Mardis, Elaine R.
Published: 2010
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25. Chapter 24 Large–Scale Complementary DNA Sequencing Methods

Author: Fulton, Lucinda L., primary, Hillier, LaDeana, additional, and Wilson, Richard K., additional
Published: 1995
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26. The role of rare protein-coding variants to anti-TNF treatment response in rheumatoid arthritis

Author: Cui, Jing, Diogo, Dorothee, Stahl, Eli A, Canhao, Helena, Mariette, Xavier, Greenberg, Jeffrey D, Okada, Yukinori, Pappas, Dimitrios A, Fulton, Robert S, Tak, Paul P, Nurmohamed, Michael T, Lee, Annette, Larson, David E, Kurreeman, Fina, Deluca, Tracie L, O'Laughlin, Michelle, Fronick, Catrina C, Fulton, Lucinda L, Mardis, Elaine R, van der Horst-Bruinsma, Irene E, Wolbink, Gert-Jan, Gregersen, Peter K, Kremer, Joel M, Crusius, J Bart A, de Vries, Niek, Huizinga, Tom W J, Fonseca, João Eurico, Miceli-Richard, Corinne, Karlson, Elizabeth W, Coenen, Marieke Jh, Barton, Anne, Plenge, Robert M, Raychaudhuri, Soumya, AII - Inflammatory diseases, Rheumatology, and ICaR - Circulation and metabolism
Abstract: Objective Many rheumatoid arthritis (RA) patients have their disease controlled with anti-tumor necrosis factor alpha (anti-TNF) biologic therapies. However, a significant number of RA patients fail to respond to anti-TNF therapy. Here, we hypothesized that rare and low-frequency variants might influence anti-TNF treatment response. Methods We sequenced the coding region of 750 genes in 1,094 RA patients of European ancestry treated with anti-TNF medications. After quality control, we included 690 genes in the analysis. We applied single variants association and gene-based association tests to identify variants associated with anti-TNF treatment response. We also performed gene set analyses of 27 TNF pathway genes, considering TNF's key mechanistic role. Results We identified 14,420 functional variants, of which 6,934 were predicted as non-synonymous where 2,136 were further predicted to be damaging. Despite being a well-powered study, no single variant or gene showed study-wide significant association with change in disease activity outcome or EULAR response outcome. Intriguingly, we observed 3 genes, out of 27 with nominal signals of association (P
Published: 2017

27. Brief Report: The Role of Rare Protein‐Coding Variants in Anti–Tumor Necrosis Factor Treatment Response in Rheumatoid Arthritis

Author: Cui, Jing, primary, Diogo, Dorothee, additional, Stahl, Eli A., additional, Canhao, Helena, additional, Mariette, Xavier, additional, Greenberg, Jeffrey D., additional, Okada, Yukinori, additional, Pappas, Dimitrios A., additional, Fulton, Robert S., additional, Tak, Paul P., additional, Nurmohamed, Michael T., additional, Lee, Annette, additional, Larson, David E., additional, Kurreeman, Fina, additional, Deluca, Tracie L., additional, O'Laughlin, Michelle, additional, Fronick, Catrina C., additional, Fulton, Lucinda L., additional, Mardis, Elaine R., additional, van der Horst‐Bruinsma, Irene E., additional, Wolbink, Gert‐Jan, additional, Gregersen, Peter K., additional, Kremer, Joel M., additional, Crusius, J. Bart A., additional, de Vries, Niek, additional, Huizinga, Tom W. J., additional, Fonseca, João Eurico, additional, Miceli‐Richard, Corinne, additional, Karlson, Elizabeth W., additional, Coenen, Marieke J. H., additional, Barton, Anne, additional, Plenge, Robert M., additional, and Raychaudhuri, Soumya, additional
Published: 2017
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28. TYK2 Protein-Coding Variants Protect against Rheumatoid Arthritis and Autoimmunity, with No Evidence of Major Pleiotropic Effects on Non-Autoimmune Complex Traits

Author: Diogo, Dorothée, Bastarache, Lisa, Liao, Katherine P., Graham, Robert R., Fulton, Robert S., Greenberg, Jeffrey D., Eyre, Steve, Bowes, John, Cui, Jing, Lee, Annette, Pappas, Dimitrios A., Kremer, Joel M., Barton, Anne, Coenen, Marieke J. H., Franke, Barbara, Kiemeney, Lambertus A., Mariette, Xavier, Richard-Miceli, Corrine, Canhão, Helena, Fonseca, João E., De Vries, Niek, P. Tak, Paul, Crusius, J. Bart A., Nurmohamed, Michael T., Kurreeman, Fina, Mikuls, Ted R., Okada, Yukinori, Stahl, Eli A., Larson, David E., Deluca, Tracie L., O'Laughlin, Michelle, Fronick, Catrina C., Fulton, Lucinda L., Kosoy, Roman, Ransom, Michael, Bhangale, Tushar R., Ortmann, Ward, Cagan, Andrew, Gainer, Vivian, Karlson, Elizabeth W., Kohane, Isaac, Murphy, Shawn N., Martin, Javier, Zhernakova, Alexandra, Klareskog, Lars, Padyukov, Leonid, Worthington, Jane, Mardis, Elaine R., Seldin, Michael F., Gregersen, Peter K., Behrens, Timothy, Raychaudhuri, Soumya, Denny, Joshua C., Plenge, Robert M., and Columbia University. Medicine
Subjects: Systemic lupus erythematosus, Phenotype, Autoimmune diseases--Treatment, Rheumatoid arthritis--Treatment, FOS: Biological sciences, FOS: Clinical medicine, Immunology, Genetics, Medicine, Inflammatory bowel diseases, Protein-tyrosine kinase
Abstract: Despite the success of genome-wide association studies (GWAS) in detecting a large number of loci for complex phenotypes such as rheumatoid arthritis (RA) susceptibility, the lack of information on the causal genes leaves important challenges to interpret GWAS results in the context of the disease biology. Here, we genetically fine-map the RA risk locus at 19p13 to define causal variants, and explore the pleiotropic effects of these same variants in other complex traits. First, we combined Immunochip dense genotyping (n = 23,092 case/control samples), Exomechip genotyping (n = 18,409 case/control samples) and targeted exon-sequencing (n = 2,236 case/controls samples) to demonstrate that three protein-coding variants in TYK2 (tyrosine kinase 2) independently protect against RA: P1104A (rs34536443, OR = 0.66, P = 2.3x10-21), A928V (rs35018800, OR = 0.53, P = 1.2x10-9), and I684S (rs12720356, OR = 0.86, P = 4.6x10-7). Second, we show that the same three TYK2 variants protect against systemic lupus erythematosus (SLE, Pomnibus = 6x10-18), and provide suggestive evidence that two of the TYK2 variants (P1104A and A928V) may also protect against inflammatory bowel disease (IBD; Pomnibus = 0.005). Finally, in a phenomewide association study (PheWAS) assessing >500 phenotypes using electronic medical records (EMR) in >29,000 subjects, we found no convincing evidence for association of P1104A and A928V with complex phenotypes other than autoimmune diseases such as RA, SLE and IBD. Together, our results demonstrate the role of TYK2 in the pathogenesis of RA, SLE and IBD, and provide supporting evidence for TYK2 as a promising drug target for the treatment of autoimmune diseases.
Published: 2015
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29. The genomic landscape of core-binding factor acute myeloid leukemias

Author: Faber, Zachary J, primary, Chen, Xiang, additional, Gedman, Amanda Larson, additional, Boggs, Kristy, additional, Cheng, Jinjun, additional, Ma, Jing, additional, Radtke, Ina, additional, Chao, Jyh-Rong, additional, Walsh, Michael P, additional, Song, Guangchun, additional, Andersson, Anna K, additional, Dang, Jinjun, additional, Dong, Li, additional, Liu, Yu, additional, Huether, Robert, additional, Cai, Zhongling, additional, Mulder, Heather, additional, Wu, Gang, additional, Edmonson, Michael, additional, Rusch, Michael, additional, Qu, Chunxu, additional, Li, Yongjin, additional, Vadodaria, Bhavin, additional, Wang, Jianmin, additional, Hedlund, Erin, additional, Cao, Xueyuan, additional, Yergeau, Donald, additional, Nakitandwe, Joy, additional, Pounds, Stanley B, additional, Shurtleff, Sheila, additional, Fulton, Robert S, additional, Fulton, Lucinda L, additional, Easton, John, additional, Parganas, Evan, additional, Pui, Ching-Hon, additional, Rubnitz, Jeffrey E, additional, Ding, Li, additional, Mardis, Elaine R, additional, Wilson, Richard K, additional, Gruber, Tanja A, additional, Mullighan, Charles G, additional, Schlenk, Richard F, additional, Paschka, Peter, additional, Döhner, Konstanze, additional, Döhner, Hartmut, additional, Bullinger, Lars, additional, Zhang, Jinghui, additional, Klco, Jeffery M, additional, and Downing, James R, additional
Published: 2016
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30. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia

Author: Ley, Timothy, Miller, Christopher, Ding, Li, Raphael, Benjamin J., Mungall, Andrew J., Robertson, A. Gordon, Hoadley, Katherine, Triche, Timothy J., Laird, Peter W., Baty, Jack D., Fulton, Lucinda L., Fulton, Robert, Heath, Sharon E., Kalicki Veizer, Joelle, Kandoth, Cyriac, Klco, Jeffery M., Koboldt, Daniel C., Kanchi, Krishna Latha, Shashikant, Kulkarni, M. S., P. h. D., F. A. C. M. G., Lamprecht, Tamara L., B. S., Washington, University, Louis, S. t., Larson, David E., P. h. D., Ling, Lin, M. S., Charles, Lu, Mclellan, Michael D., Mcmichael, Joshua F., the Genome Institute at Washington University, Jacqueline, Payton, M. D., P. h. D., Heather, Schmidt, Spencer, David H., Tomasson, Michael H., M. D., Siteman Cancer Center, S. t. Louis, Wallis, John W., Wartman, Lukas D., Watson, Mark A., John, Welch, Wendl, Michael C., Adrian, Ally, B. S. c., Miruna, Balasundaram, B. A. S. c., Inanc, Birol, Yaron, Butterfield, Readman, Chiu, M. S. c., Andy, Chu, Eric, Chuah, Hye Jung Chun, Richard, Corbett, Noreen, Dhalla, Ranabir, Guin, An, He, Carrie, Hirst, Martin, Hirst, Holt, Robert A., Steven, Jones, Aly, Karsan, Darlene, Lee, Haiyan I., Li, Marra, Marco A., Michael, Mayo, Moore, Richard A., Karen, Mungall, Jeremy, Parker, Erin, Pleasance, Patrick, Plettner, Jacquie, Schein, Dominik, Stoll, Lucas, Swanson, Angela, Tam, Nina, Thiessen, Richard, Varhol, Natasja, Wye, Yongjun, Zhao, M. S. c., D. V. M., British Columbia Cancer Agency's Genome Sciences Centre, Vancouver, Canada, Stacey, Gabriel, Gad, Getz, Carrie, Sougnez, Lihua, Zou, Broad Institute of Harvard, Massachusetts Institute of Technology, Cambridge, Ma, Mark D. M. Leiserson, B. A., Vandin, Fabio, Hsin Ta Wu, Brown, University, Center for Computational Molecular Biology, Providence, Ri, Frederick, Applebaum, Fred Hutchinson Cancer Research Center, Division of Medical Oncology, Seattle Cancer Care Alliance, Seattle, Baylin, Stephen B., Johns Hopkins University, Baltimore, Rehan, Akbani, Broom, Bradley M., Ken, Chen, Motter, Thomas C., B. A., Khanh, Nguyen, Weinstein, John N., Nianziang, Zhang, Anderson Cancer Center, University of Texas M. D., Houston, Ferguson, Martin L., Mlf, Consulting, Biotechnology Consultant, Boston, Christopher, Adams, Aaron, Black, Jay, Bowen, Julie Gastier Foster, Thomas, Grossman, Tara, Lichtenberg, Lisa, Wise, the Research Institute at Nationwide Children's Hospital, Columbus, Oh, Tanja, Davidsen, Demchok, John A., Mills Shaw, Kenna R., Margi, Sheth, National Cancer Institute, Bethesda, Md, Sofia, Heidi J., P. h. D., M. P. H., National Human Genome Research Institute, Liming, Yang, Downing, James R., Jude Children's Research Hospital, S. t., Memphis, Greg, Eley, Sciementis, Llc, Statham, Ga, Shelley, Alonso, Brenda, Ayala, Julien, Baboud, Mark, Backus, Barletta, Sean P., Berton, Dominique L., M. S. C. S., Chu, Anna L., Stanley, Girshik, Jensen, Mark A., Ari, Kahn, Prachi, Kothiyal, Nicholls, Matthew C., Pihl, Todd D., Pot, David A., Rohini, Raman, B. E., Sanbhadti, Rashmi N., Snyder, Eric E., Deepak, Srinivasan, Jessica, Walton, Yunhu, Wan, Zhining, Wang, Sra, International, Fairfax, Va, Issa, Jean Pierre J., Temple, University, Philadelphia, Michelle Le Beau, University of Chicago, Chicago, Martin, Carroll, University of Pennsylvania, Hagop Kantarjian, M. D., Steven, Kornblau, Bootwalla, Moiz S., B. S. c., M. S., Lai, Phillip H., Hui, Shen, Van Den Berg, David J., Weisenberger, Daniel J., University of Southern California, Epigenome, Center, Los, Angeles, Daniel C. Link, M. D., Walter, Matthew J., Ozenberger, Bradley A., Mardis, Elaine R., Peter, Westervelt, Graubert, Timothy A., Dipersio, John F., and Wilson, Richard K.
Subjects: Myeloid, Adult, Epigenomics, Male, NPM1, Gene Expression, CpG Islands, DNA Methylation, Female, Gene Fusion, Genome, Human, Humans, Leukemia, Myeloid, Acute, MicroRNAs, Middle Aged, Sequence Analysis, DNA, Mutation, Acute, Enasidenib, Biology, CEBPA, Genetics, Genome, Leukemia, Massive parallel sequencing, MicroRNA sequencing, Myeloid leukemia, DNA, General Medicine, KMT2A, biology.protein, Sequence Analysis, Nucleophosmin, Human, Comparative genomic hybridization
Abstract: BACKGROUND—Many mutations that contribute to the pathogenesis of acute myeloid leukemia (AML) are undefined. The relationships between patterns of mutations and epigenetic phenotypes are not yet clear. METHODS—We analyzed the genomes of 200 clinically annotated adult cases of de novo AML, using either whole-genome sequencing (50 cases) or whole-exome sequencing (150 cases), along with RNA and microRNA sequencing and DNA-methylation analysis. RESULTS—AML genomes have fewer mutations than most other adult cancers, with an average of only 13 mutations found in genes. Of these, an average of 5 are in genes that are recurrently mutated in AML. A total of 23 genes were significantly mutated, and another 237 were mutated in two or more samples. Nearly all samples had at least 1 nonsynonymous mutation in one of nine categories of genes that are almost certainly relevant for pathogenesis, including transcriptionfactor fusions (18% of cases), the gene encoding nucleophosmin (NPM1) (27%), tumorsuppressor genes (16%), DNA-methylation–related genes (44%), signaling genes (59%), chromatin-modifying genes (30%), myeloid transcription-factor genes (22%), cohesin-complex genes (13%), and spliceosome-complex genes (14%). Patterns of cooperation and mutual exclusivity suggested strong biologic relationships among several of the genes and categories. CONCLUSIONS—We identified at least one potential driver mutation in nearly all AML samples and found that a complex interplay of genetic events contributes to AML pathogenesis in individual patients. The databases from this study are widely available to serve as a foundation for further investigations of AML pathogenesis, classification, and risk stratification. (Funded by the National Institutes of Health.) The molecular pathogenesis of acute myeloid leukemia (AML) has been studied with the use of cytogenetic analysis for more than three decades. Recurrent chromosomal structural variations are well established as diagnostic and prognostic markers, suggesting that acquired genetic abnormalities (i.e., somatic mutations) have an essential role in pathogenesis. 1,2 However, nearly 50% of AML samples have a normal karyotype, and many of these genomes lack structural abnormalities, even when assessed with high-density comparative genomic hybridization or single-nucleotide polymorphism (SNP) arrays 3-5 (see Glossary). Targeted sequencing has identified recurrent mutations in FLT3, NPM1, KIT, CEBPA, and TET2. 6-8 Massively parallel sequencing enabled the discovery of recurrent mutations in DNMT3A 9,10 and IDH1. 11 Recent studies have shown that many patients with
Published: 2013

31. Comprehensive molecular portraits of human breast tumours

Author: Moore, Richard A., Fulton, Lucinda L., Hirst, Martin, Chun, Hye-Jung E., Fulton, Robert S., Mardis, Elaine R., Dhalla, Noreen, Ally, Adrian, Koboldt, Daniel C., Dooling, David J., Chuah, Eric, Holt, Robert A., Ding, Li, Kalicki-Veizer, Joelle, Chu, Andy, Mungall, Andrew J., Butterfield, Yaron S. N., Li, Haiyan I., Pleasance, Erin, Schmidt, Heather, Carlsen, Rebecca, Carter, Candace, McLellan, Michael D., Balasundaram, Miruna, Hirst, Carrie, Guin, Ranabir, Lee, Darlene, Coope, Robin J. N., Wilson, Richard K., McMichael, Joshua F., Mayo, Michael, and Gordon Robertson, A.
Subjects: skin and connective tissue diseases
Abstract: This Article from the Cancer Genome Atlas consortium describes a multifaceted analysis of primary breast cancers in 825 people. Exome sequencing, copy number variation, DNA methylation, messenger RNA arrays, microRNA sequencing and proteomic analyses were performed and integrated to shed light on breast-cancer heterogeneity. Just three genes — TP53, PIK3CA and GATA3 — are mutated at greater than 10% frequency across all breast cancers. Many subtype-associated and novel mutations were identified, as well as two breast-cancer subgroups with specific signalling-pathway signatures. The analyses also suggest that much of the clinically observable plasticity and heterogeneity occurs within, and not across, the major subtypes of breast cancer.
Published: 2012
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32. TYK2 Protein-Coding Variants Protect against Rheumatoid Arthritis and Autoimmunity, with No Evidence of Major Pleiotropic Effects on Non-Autoimmune Complex Traits

Author: Diogo, Dorothée, primary, Bastarache, Lisa, additional, Liao, Katherine P., additional, Graham, Robert R., additional, Fulton, Robert S., additional, Greenberg, Jeffrey D., additional, Eyre, Steve, additional, Bowes, John, additional, Cui, Jing, additional, Lee, Annette, additional, Pappas, Dimitrios A., additional, Kremer, Joel M., additional, Barton, Anne, additional, Coenen, Marieke J. H., additional, Franke, Barbara, additional, Kiemeney, Lambertus A., additional, Mariette, Xavier, additional, Richard-Miceli, Corrine, additional, Canhão, Helena, additional, Fonseca, João E., additional, de Vries, Niek, additional, Tak, Paul P., additional, Crusius, J. Bart A., additional, Nurmohamed, Michael T., additional, Kurreeman, Fina, additional, Mikuls, Ted R., additional, Okada, Yukinori, additional, Stahl, Eli A., additional, Larson, David E., additional, Deluca, Tracie L., additional, O'Laughlin, Michelle, additional, Fronick, Catrina C., additional, Fulton, Lucinda L., additional, Kosoy, Roman, additional, Ransom, Michael, additional, Bhangale, Tushar R., additional, Ortmann, Ward, additional, Cagan, Andrew, additional, Gainer, Vivian, additional, Karlson, Elizabeth W., additional, Kohane, Isaac, additional, Murphy, Shawn N., additional, Martin, Javier, additional, Zhernakova, Alexandra, additional, Klareskog, Lars, additional, Padyukov, Leonid, additional, Worthington, Jane, additional, Mardis, Elaine R., additional, Seldin, Michael F., additional, Gregersen, Peter K., additional, Behrens, Timothy, additional, Raychaudhuri, Soumya, additional, Denny, Joshua C., additional, and Plenge, Robert M., additional
Published: 2015
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33. Genome remodelling in a basal-like breast cancer metastasis and xenograft

Author: McLellan, Michael D., Ellis, Matthew J., Tao, Yu, Lin, Li, Vickery, Tammi L., Fulton, Lucinda L., Lin, Ling, Koboldt, Daniel C., Appelbaum, Elizabeth, DeSchryver, Katherine, Zhang, Qunyuan, Schmidt, Heather, Ding, Li, Wallis, John W., Crowder, Robert, Kalicki, Joelle, Larson, David E., McMichael, Joshua F., Fulton, Robert S., Hoog, Jeremy, Li, Shunqiang, Chen, Ken, Cook, Lisa, Magrini, Vincent J., Chen, Lei, Davies, Sherri, Wendl, Michael C., Abbott, Rachel M., Guintoli, Therese, McGrath, Sean D., Harris, Christopher C., and Dooling, David J.
Abstract: Massively parallel DNA sequencing technologies provide an unprecedented ability to screen entire genomes for genetic changes associated with tumor progression. Here we describe the genomic analyses of four DNA samples from an African-American patient with basal-like breast cancer: peripheral blood, the primary tumor, a brain metastasis, and a xenograft derived from the primary tumor. The metastasis contained two de novo mutations and a large deletion not present in the primary tumor, and was significantly enriched for 20 shared mutations. The xenograft retained all primary tumor mutations, and displayed a mutation enrichment pattern that paralleled the metastasis (16 of 20 genes). Two overlapping large deletions, encompassing CTNNA1, were present in all three tumor samples. The differential mutation frequencies and structural variation patterns in metastasis and xenograft compared to the primary tumor suggest that secondary tumors may arise from a minority of cells within the primary.
Published: 2010
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34. 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., Hayes, D. Neil, 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., Byers, Lauren Averett, 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 S. N., 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, Robertson, A. Gordon, Wye, Natasja, Thiessen, Nina, Holt, Robert A., Jones, Steven J. M., Marra, Marco A., Imielinski, Marcin, Onofrio, Robert C., Hodis, Eran, Zack, Travis, Helman, Elena, Pedamallu, Chandra Sekhar, Mesirov, Jill, Saksena, Gordon, Schumacher, Steven E., Carter, Scott L., Garraway, Levi, Beroukhim, Rameen, Lee, Semin, Mahadeshwar, Harshad S., Pantazi, Angeliki, Protopopov, Alexei, Ren, Xiaojia, Seth, Sahil, Song, Xingzhi, Tang, Jiabin, Yang, Lixing, Zhang, Jianhua, Chen, Peng-Chieh, Parfenov, Michael, Xu, Andrew Wei, Santoso, Netty, Chin, Lynda, Park, Peter J., Hoadley, Katherine A., Auman, J. Todd, Meng, Shaowu, Shi, Yan, Buda, Elizabeth, Waring, Scot, Veluvolu, Umadevi, Tan, Donghui, Mieczkowski, Piotr A., Jones, Corbin D., Simons, Janae V., Soloway, Matthew G., Bodenheimer, Tom, Jefferys, Stuart R., Roach, Jeffrey, Hoyle, Alan P., Wu, Junyuan, Balu, Saianand, Singh, Darshan, Prins, Jan F., Marron, J. S., Parker, Joel S., Perou, Charles M., Liu, Jinze, Maglinte, Dennis T., Lai, Philip H., Bootwalla, Moiz S., Van Den Berg, David J., Triche, Timothy, Jr., Cho, Juok, DiCara, Daniel, Heiman, David, Lin, Pei, Mallard, William, Voet, Douglas, Zhang, Hailei, Zou, Lihua, Noble, Michael S., Gehlenborg, Nils, Thorvaldsdottir, Helga, Nazaire, Marc-Danie, Robinson, Jim, Aksoy, B. Arman, Ciriello, Giovanni, Taylor, Barry S., Dresdner, Gideon, Gao, Jianjiong, Gross, Benjamin, Seshan, Venkatraman E., Reva, Boris, Sumer, S. Onur, Weinhold, Nils, Sander, Chris, Zhu, Jingchun, Benz, Christopher C., Yau, Christina, Haussler, David, Spellman, Paul T., Kimes, Patrick K., Broom, Bradley M., Wang, Jing, Lu, Yiling, Diao, Lixia, Liu, Wenbin, Amos, Christopher I., Akbani, Rehan, Mills, Gordon B., Curley, Erin, Paulauskis, Joseph, Lau, Kevin, Morris, Scott, Shelton, Troy, Mallery, David, Gardner, Johanna, Penny, Robert, Saller, Charles, Tarvin, Katherine, Richards, William G., Cerfolio, Robert, Bryant, Ayesha, Raymond, Daniel P., Pennell, Nathan A., Farver, Carol, Czerwinski, Christine, Huelsenbeck-Dill, Lori, Iacocca, Mary, Petrelli, Nicholas, Rabeno, Brenda, Brown, Jennifer, Bauer, Thomas, Dolzhanskiy, Oleg, Potapova, Olga, Rotin, Daniil, Voronina, Olga, Nemirovich-Danchenko, Elena, Fedosenko, Konstantin V., Gal, Anthony, Behera, Madhusmita, Ramalingam, Suresh S., Sica, Gabriel, Flieder, Douglas, Boyd, Jeff, Weaver, JoEllen, Kohl, Bernard, Sandusky, George, Juhl, Hartmut, Duhig, Edwina, Illei, Peter, Gabrielson, Edward, Shin, James, Lee, Beverly, Rogers, Kristen, Trusty, Dante, Brock, Malcolm V., Williamson, Christina, Burks, Eric, Rieger-Christ, Kimberly, Holway, Antonia, Sullivan, Travis, Asiedu, Michael K., Kosari, Farhad, Rekhtman, Natasha, Zakowski, Maureen, Rusch, Valerie W., Zippile, Paul, Suh, James, Pass, Harvey, Goparaju, Chandra, Owusu-Sarpong, Yvonne, Bartlett, John M. S., Kodeeswaran, Sugy, Parfitt, Jeremy, Sekhon, Harmanjatinder, Albert, Monique, Eckman, John, Myers, Jerome B., Cheney, Richard, Morrison, Carl, Gaudioso, Carmelo, Borgia, Jeffrey A., Bonomi, Philip, Pool, Mark, Liptay, Michael J., Moiseenko, Fedor, Zaytseva, Irina, Dienemann, Hendrik, Meister, Michael, Schnabel, Philipp A., Muley, Thomas R., Peifer, Martin, Gomez-Fernandez, Carmen, Herbert, Lynn, Egea, Sophie, Huang, Mei, Thorne, Leigh B., Boice, Lori, Salazar, Ashley Hill, Funkhouser, William K., Rathmell, W. Kimryn, Dhir, Rajiv, Yousem, Samuel A., Dacic, Sanja, Schneider, Frank, Siegfried, Jill M., Hajek, Richard, Watson, Mark A., McDonald, Sandra, Meyers, Bryan, Clarke, Belinda, Yang, Ian A., Fong, Kwun M., Hunter, Lindy, Windsor, Morgan, Bowman, Rayleen V., Peters, Solange, Letovanec, Igor, Khan, Khurram Z., Jensen, Mark A., Snyder, Eric E., Srinivasan, Deepak, Kahn, Ari B., Baboud, Julien, Pot, David A., Shaw, Kenna R. Mills, Sheth, Margi, Davidsen, Tanja, Demchok, John A., Yang, Liming, Wang, Zhining, Tarnuzzer, Roy, Zenklusen, Jean Claude, Ozenberger, Bradley A., Sofia, Heidi J., 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., Hayes, D. Neil, 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., Byers, Lauren Averett, 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 S. N., 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, Robertson, A. Gordon, Wye, Natasja, Thiessen, Nina, Holt, Robert A., Jones, Steven J. M., Marra, Marco A., Imielinski, Marcin, Onofrio, Robert C., Hodis, Eran, Zack, Travis, Helman, Elena, Pedamallu, Chandra Sekhar, Mesirov, Jill, Saksena, Gordon, Schumacher, Steven E., Carter, Scott L., Garraway, Levi, Beroukhim, Rameen, Lee, Semin, Mahadeshwar, Harshad S., Pantazi, Angeliki, Protopopov, Alexei, Ren, Xiaojia, Seth, Sahil, Song, Xingzhi, Tang, Jiabin, Yang, Lixing, Zhang, Jianhua, Chen, Peng-Chieh, Parfenov, Michael, Xu, Andrew Wei, Santoso, Netty, Chin, Lynda, Park, Peter J., Hoadley, Katherine A., Auman, J. Todd, Meng, Shaowu, Shi, Yan, Buda, Elizabeth, Waring, Scot, Veluvolu, Umadevi, Tan, Donghui, Mieczkowski, Piotr A., Jones, Corbin D., Simons, Janae V., Soloway, Matthew G., Bodenheimer, Tom, Jefferys, Stuart R., Roach, Jeffrey, Hoyle, Alan P., Wu, Junyuan, Balu, Saianand, Singh, Darshan, Prins, Jan F., Marron, J. S., Parker, Joel S., Perou, Charles M., Liu, Jinze, Maglinte, Dennis T., Lai, Philip H., Bootwalla, Moiz S., Van Den Berg, David J., Triche, Timothy, Jr., Cho, Juok, DiCara, Daniel, Heiman, David, Lin, Pei, Mallard, William, Voet, Douglas, Zhang, Hailei, Zou, Lihua, Noble, Michael S., Gehlenborg, Nils, Thorvaldsdottir, Helga, Nazaire, Marc-Danie, Robinson, Jim, Aksoy, B. Arman, Ciriello, Giovanni, Taylor, Barry S., Dresdner, Gideon, Gao, Jianjiong, Gross, Benjamin, Seshan, Venkatraman E., Reva, Boris, Sumer, S. Onur, Weinhold, Nils, Sander, Chris, Zhu, Jingchun, Benz, Christopher C., Yau, Christina, Haussler, David, Spellman, Paul T., Kimes, Patrick K., Broom, Bradley M., Wang, Jing, Lu, Yiling, Diao, Lixia, Liu, Wenbin, Amos, Christopher I., Akbani, Rehan, Mills, Gordon B., Curley, Erin, Paulauskis, Joseph, Lau, Kevin, Morris, Scott, Shelton, Troy, Mallery, David, Gardner, Johanna, Penny, Robert, Saller, Charles, Tarvin, Katherine, Richards, William G., Cerfolio, Robert, Bryant, Ayesha, Raymond, Daniel P., Pennell, Nathan A., Farver, Carol, Czerwinski, Christine, Huelsenbeck-Dill, Lori, Iacocca, Mary, Petrelli, Nicholas, Rabeno, Brenda, Brown, Jennifer, Bauer, Thomas, Dolzhanskiy, Oleg, Potapova, Olga, Rotin, Daniil, Voronina, Olga, Nemirovich-Danchenko, Elena, Fedosenko, Konstantin V., Gal, Anthony, Behera, Madhusmita, Ramalingam, Suresh S., Sica, Gabriel, Flieder, Douglas, Boyd, Jeff, Weaver, JoEllen, Kohl, Bernard, Sandusky, George, Juhl, Hartmut, Duhig, Edwina, Illei, Peter, Gabrielson, Edward, Shin, James, Lee, Beverly, Rogers, Kristen, Trusty, Dante, Brock, Malcolm V., Williamson, Christina, Burks, Eric, Rieger-Christ, Kimberly, Holway, Antonia, Sullivan, Travis, Asiedu, Michael K., Kosari, Farhad, Rekhtman, Natasha, Zakowski, Maureen, Rusch, Valerie W., Zippile, Paul, Suh, James, Pass, Harvey, Goparaju, Chandra, Owusu-Sarpong, Yvonne, Bartlett, John M. S., Kodeeswaran, Sugy, Parfitt, Jeremy, Sekhon, Harmanjatinder, Albert, Monique, Eckman, John, Myers, Jerome B., Cheney, Richard, Morrison, Carl, Gaudioso, Carmelo, Borgia, Jeffrey A., Bonomi, Philip, Pool, Mark, Liptay, Michael J., Moiseenko, Fedor, Zaytseva, Irina, Dienemann, Hendrik, Meister, Michael, Schnabel, Philipp A., Muley, Thomas R., Peifer, Martin, Gomez-Fernandez, Carmen, Herbert, Lynn, Egea, Sophie, Huang, Mei, Thorne, Leigh B., Boice, Lori, Salazar, Ashley Hill, Funkhouser, William K., Rathmell, W. Kimryn, Dhir, Rajiv, Yousem, Samuel A., Dacic, Sanja, Schneider, Frank, Siegfried, Jill M., Hajek, Richard, Watson, Mark A., McDonald, Sandra, Meyers, Bryan, Clarke, Belinda, Yang, Ian A., Fong, Kwun M., Hunter, Lindy, Windsor, Morgan, Bowman, Rayleen V., Peters, Solange, Letovanec, Igor, Khan, Khurram Z., Jensen, Mark A., Snyder, Eric E., Srinivasan, Deepak, Kahn, Ari B., Baboud, Julien, Pot, David A., Shaw, Kenna R. Mills, Sheth, Margi, Davidsen, Tanja, Demchok, John A., Yang, Liming, Wang, Zhining, Tarnuzzer, Roy, Zenklusen, Jean Claude, Ozenberger, Bradley A., and Sofia, Heidi J.
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

35. Whole Genome Sequence of the Treponema pallidum subsp. endemicum Strain Bosnia A: The Genome Is Related to Yaws Treponemes but Contains Few Loci Similar to Syphilis Treponemes

Author: Štaudová, Barbora, primary, Strouhal, Michal, additional, Zobaníková, Marie, additional, Čejková, Darina, additional, Fulton, Lucinda L., additional, Chen, Lei, additional, Giacani, Lorenzo, additional, Centurion-Lara, Arturo, additional, Bruisten, Sylvia M., additional, Sodergren, Erica, additional, Weinstock, George M., additional, and Šmajs, David, additional
Published: 2014
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36. Clonal Architecture of Secondary Acute Myeloid Leukemia Defined by Single-Cell Sequencing

Author: Hughes, Andrew E. O., primary, Magrini, Vincent, additional, Demeter, Ryan, additional, Miller, Christopher A., additional, Fulton, Robert, additional, Fulton, Lucinda L., additional, Eades, William C., additional, Elliott, Kevin, additional, Heath, Sharon, additional, Westervelt, Peter, additional, Ding, Li, additional, Conrad, Donald F., additional, White, Brian S., additional, Shao, Jin, additional, Link, Daniel C., additional, DiPersio, John F., additional, Mardis, Elaine R., additional, Wilson, Richard K., additional, Ley, Timothy J., additional, Walter, Matthew J., additional, and Graubert, Timothy A., additional
Published: 2014
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37. Erratum: Corrigendum: C11orf95–RELA fusions drive oncogenic NF-κB signalling in ependymoma

Author: Parker, Matthew, primary, Mohankumar, Kumarasamypet M., additional, Punchihewa, Chandanamali, additional, Weinlich, Ricardo, additional, Dalton, James D., additional, Li, Yongjin, additional, Lee, Ryan, additional, Tatevossian, Ruth G., additional, Phoenix, Timothy N., additional, Thiruvenkatam, Radhika, additional, White, Elsie, additional, Tang, Bo, additional, Orisme, Wilda, additional, Gupta, Kirti, additional, Rusch, Michael, additional, Chen, Xiang, additional, Li, Yuxin, additional, Nagahawhatte, Panduka, additional, Hedlund, Erin, additional, Finkelstein, David, additional, Wu, Gang, additional, Shurtleff, Sheila, additional, Easton, John, additional, Boggs, Kristy, additional, Yergeau, Donald, additional, Vadodaria, Bhavin, additional, Mulder, Heather L., additional, Becksfort, Jared, additional, Gupta, Pankaj, additional, Huether, Robert, additional, Ma, Jing, additional, Song, Guangchun, additional, Gajjar, Amar, additional, Merchant, Thomas, additional, Boop, Frederick, additional, Smith, Amy A., additional, Ding, Li, additional, Lu, Charles, additional, Ochoa, Kerri, additional, Zhao, David, additional, Fulton, Robert S., additional, Fulton, Lucinda L., additional, Mardis, Elaine R., additional, Wilson, Richard K., additional, Downing, James R., additional, Green, Douglas R., additional, Zhang, Jinghui, additional, Ellison, David W., additional, and Gilbertson, Richard J., additional
Published: 2014
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38. The Somatic Genomic Landscape of Glioblastoma

Author: Brennan, Cameron W., primary, Verhaak, Roel G.W., additional, McKenna, Aaron, additional, Campos, Benito, additional, Noushmehr, Houtan, additional, Salama, Sofie R., additional, Zheng, Siyuan, additional, Chakravarty, Debyani, additional, Sanborn, J. Zachary, additional, Berman, Samuel H., additional, Beroukhim, Rameen, additional, Bernard, Brady, additional, Wu, Chang-Jiun, additional, Genovese, Giannicola, additional, Shmulevich, Ilya, additional, Barnholtz-Sloan, Jill, additional, Zou, Lihua, additional, Vegesna, Rahulsimham, additional, Shukla, Sachet A., additional, Ciriello, Giovanni, additional, Yung, W.K., additional, Zhang, Wei, additional, Sougnez, Carrie, additional, Mikkelsen, Tom, additional, Aldape, Kenneth, additional, Bigner, Darell D., additional, Van Meir, Erwin G., additional, Prados, Michael, additional, Sloan, Andrew, additional, Black, Keith L., additional, Eschbacher, Jennifer, additional, Finocchiaro, Gaetano, additional, Friedman, William, additional, Andrews, David W., additional, Guha, Abhijit, additional, Iacocca, Mary, additional, O’Neill, Brian P., additional, Foltz, Greg, additional, Myers, Jerome, additional, Weisenberger, Daniel J., additional, Penny, Robert, additional, Kucherlapati, Raju, additional, Perou, Charles M., additional, Hayes, D. Neil, additional, Gibbs, Richard, additional, Marra, Marco, additional, Mills, Gordon B., additional, Lander, Eric, additional, Spellman, Paul, additional, Wilson, Richard, additional, Sander, Chris, additional, Weinstein, John, additional, Meyerson, Matthew, additional, Gabriel, Stacey, additional, Laird, Peter W., additional, Haussler, David, additional, Getz, Gad, additional, Chin, Lynda, additional, Benz, Christopher, additional, Barrett, Wendi, additional, Ostrom, Quinn, additional, Wolinsky, Yingli, additional, Bose, Bikash, additional, Boulos, Paul T., additional, Boulos, Madgy, additional, Brown, Jenn, additional, Czerinski, Christine, additional, Eppley, Matthew, additional, Kempista, Thelma, additional, Kitko, Teresa, additional, Koyfman, Yakov, additional, Rabeno, Brenda, additional, Rastogi, Pawan, additional, Sugarman, Michael, additional, Swanson, Patricia, additional, Yalamanchii, Kennedy, additional, Otey, Ilana P., additional, Liu, Yingchun Spring, additional, Xiao, Yonghong, additional, Auman, J.Todd, additional, Chen, Peng-Chieh, additional, Hadjipanayis, Angela, additional, Lee, Eunjung, additional, Lee, Semin, additional, Park, Peter J., additional, Seidman, Jonathan, additional, Yang, Lixing, additional, Kalkanis, Steven, additional, Poisson, Laila M., additional, Raghunathan, Aditya, additional, Scarpace, Lisa, additional, Bressler, Ryan, additional, Eakin, Andrea, additional, Iype, Lisa, additional, Kreisberg, Richard B., additional, Leinonen, Kalle, additional, Reynolds, Sheila, additional, Rovira, Hector, additional, Thorsson, Vesteinn, additional, Annala, Matti J., additional, Paulauskis, Joseph, additional, Curley, Erin, additional, Hatfield, Martha, additional, Mallery, David, additional, Morris, Scott, additional, Shelton, Troy, additional, Shelton, Candace, additional, Sherman, Mark, additional, Yena, Peggy, additional, Cuppini, Lucia, additional, DiMeco, Francesco, additional, Eoli, Marica, additional, Maderna, Emanuela, additional, Pollo, Bianca, additional, Saini, Marco, additional, Balu, Saianand, additional, Hoadley, Katherine A., additional, Li, Ling, additional, Miller, C. Ryan, additional, Shi, Yan, additional, Topal, Michael D., additional, Wu, Junyuan, additional, Dunn, Gavin, additional, Giannini, Caterina, additional, O'Neill, Brian P., additional, Aksoy, B. Arman, additional, Antipin, Yevgeniy, additional, Borsu, Laetitia, additional, Brennan, Cameron W., additional, Cerami, Ethan, additional, Gao, Jianjiong, additional, Gross, Benjamin, additional, Jacobsen, Anders, additional, Ladanyi, Marc, additional, Lash, Alex, additional, Liang, Yupu, additional, Reva, Boris, additional, Schultz, Nikolaus, additional, Shen, Ronglai, additional, Socci, Nicholas D., additional, Viale, Agnes, additional, Ferguson, Martin L., additional, Chen, Qing-Rong, additional, Demchok, John A., additional, Dillon, Laura A.L., additional, Shaw, Kenna R. Mills, additional, Sheth, Margi, additional, Tarnuzzer, Roy, additional, Wang, Zhining, additional, Yang, Liming, additional, Davidsen, Tanja, additional, Guyer, Mark S., additional, Ozenberger, Bradley A., additional, Sofia, Heidi J., additional, Bergsten, Julie, additional, Eckman, John, additional, Harr, Jodi, additional, Smith, Christine, additional, Tucker, Kelly, additional, Winemiller, Cindy, additional, Zach, Leigh Anne, additional, Ljubimova, Julia Y., additional, Eley, Greg, additional, Ayala, Brenda, additional, Jensen, Mark A., additional, Kahn, Ari, additional, Pihl, Todd D., additional, Pot, David A., additional, Wan, Yunhu, additional, Hansen, Nathan, additional, Hothi, Parvi, additional, Lin, Biaoyang, additional, Shah, Nameeta, additional, Yoon, Jae-geun, additional, Lau, Ching, additional, Berens, Michael, additional, Ardlie, Kristin, additional, Carter, Scott L., additional, Cherniack, Andrew D., additional, Noble, Mike, additional, Cho, Juok, additional, Cibulskis, Kristian, additional, DiCara, Daniel, additional, Frazer, Scott, additional, Gabriel, Stacey B., additional, Gehlenborg, Nils, additional, Gentry, Jeff, additional, Heiman, David, additional, Kim, Jaegil, additional, Jing, Rui, additional, Lander, Eric S., additional, Lawrence, Michael, additional, Lin, Pei, additional, Mallard, Will, additional, Onofrio, Robert C., additional, Saksena, Gordon, additional, Schumacher, Steve, additional, Stojanov, Petar, additional, Tabak, Barbara, additional, Voet, Doug, additional, Zhang, Hailei, additional, Dees, Nathan N., additional, Ding, Li, additional, Fulton, Lucinda L., additional, Fulton, Robert S., additional, Kanchi, Krishna-Latha, additional, Mardis, Elaine R., additional, Wilson, Richard K., additional, Baylin, Stephen B., additional, Harshyne, Larry, additional, Cohen, Mark L., additional, Devine, Karen, additional, Sloan, Andrew E., additional, VandenBerg, Scott R., additional, Berger, Mitchel S., additional, Carlin, Daniel, additional, Craft, Brian, additional, Ellrott, Kyle, additional, Goldman, Mary, additional, Goldstein, Theodore, additional, Grifford, Mia, additional, Ma, Singer, additional, Ng, Sam, additional, Stuart, Joshua, additional, Swatloski, Teresa, additional, Waltman, Peter, additional, Zhu, Jing, additional, Foss, Robin, additional, Frentzen, Barbara, additional, McTiernan, Raquel, additional, Yachnis, Anthony, additional, Mao, Yong, additional, Akbani, Rehan, additional, Bogler, Oliver, additional, Fuller, Gregory N., additional, Liu, Wenbin, additional, Liu, Yuexin, additional, Lu, Yiling, additional, Mills, Gordon, additional, Protopopov, Alexei, additional, Ren, Xiaojia, additional, Sun, Youting, additional, Yung, W.K. Alfred, additional, Zhang, Jianhua, additional, Chen, Ken, additional, Weinstein, John N., additional, Bootwalla, Moiz S., additional, Lai, Phillip H., additional, Triche, Timothy J., additional, Van Den Berg, David J., additional, Gutmann, David H., additional, Lehman, Norman L., additional, VanMeir, Erwin G., additional, Brat, Daniel, additional, Olson, Jeffrey J., additional, Mastrogianakis, Gena M., additional, Devi, Narra S., additional, Zhang, Zhaobin, additional, Bigner, Darell, additional, Lipp, Eric, additional, and McLendon, Roger, additional
Published: 2013
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39. Identification of a rare coding variant in complement 3 associated with age-related macular degeneration

Author: Zhan, Xiaowei, primary, Larson, David E, additional, Wang, Chaolong, additional, Koboldt, Daniel C, additional, Sergeev, Yuri V, additional, Fulton, Robert S, additional, Fulton, Lucinda L, additional, Fronick, Catrina C, additional, Branham, Kari E, additional, Bragg-Gresham, Jennifer, additional, Jun, Goo, additional, Hu, Youna, additional, Kang, Hyun Min, additional, Liu, Dajiang, additional, Othman, Mohammad, additional, Brooks, Matthew, additional, Ratnapriya, Rinki, additional, Boleda, Alexis, additional, Grassmann, Felix, additional, von Strachwitz, Claudia, additional, Olson, Lana M, additional, Buitendijk, Gabriëlle H S, additional, Hofman, Albert, additional, van Duijn, Cornelia M, additional, Cipriani, Valentina, additional, Moore, Anthony T, additional, Shahid, Humma, additional, Jiang, Yingda, additional, Conley, Yvette P, additional, Morgan, Denise J, additional, Kim, Ivana K, additional, Johnson, Matthew P, additional, Cantsilieris, Stuart, additional, Richardson, Andrea J, additional, Guymer, Robyn H, additional, Luo, Hongrong, additional, Ouyang, Hong, additional, Licht, Christoph, additional, Pluthero, Fred G, additional, Zhang, Mindy M, additional, Zhang, Kang, additional, Baird, Paul N, additional, Blangero, John, additional, Klein, Michael L, additional, Farrer, Lindsay A, additional, DeAngelis, Margaret M, additional, Weeks, Daniel E, additional, Gorin, Michael B, additional, Yates, John R W, additional, Klaver, Caroline C W, additional, Pericak-Vance, Margaret A, additional, Haines, Jonathan L, additional, Weber, Bernhard H F, additional, Wilson, Richard K, additional, Heckenlively, John R, additional, Chew, Emily Y, additional, Stambolian, Dwight, additional, Mardis, Elaine R, additional, Swaroop, Anand, additional, and Abecasis, Goncalo R, additional
Published: 2013
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40. Whole Genome Sequence of the Treponema Fribourg-Blanc: Unspecified Simian Isolate Is Highly Similar to the Yaws Subspecies

Author: Zobaníková, Marie, primary, Strouhal, Michal, additional, Mikalová, Lenka, additional, Čejková, Darina, additional, Ambrožová, Lenka, additional, Pospíšilová, Petra, additional, Fulton, Lucinda L., additional, Chen, Lei, additional, Sodergren, Erica, additional, Weinstock, George M., additional, and Šmajs, David, additional
Published: 2013
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41. Sequencing of the sea lamprey (Petromyzon marinus) genome provides insights into vertebrate evolution

Author: Smith, Jeramiah J, primary, Kuraku, Shigehiro, additional, Holt, Carson, additional, Sauka-Spengler, Tatjana, additional, Jiang, Ning, additional, Campbell, Michael S, additional, Yandell, Mark D, additional, Manousaki, Tereza, additional, Meyer, Axel, additional, Bloom, Ona E, additional, Morgan, Jennifer R, additional, Buxbaum, Joseph D, additional, Sachidanandam, Ravi, additional, Sims, Carrie, additional, Garruss, Alexander S, additional, Cook, Malcolm, additional, Krumlauf, Robb, additional, Wiedemann, Leanne M, additional, Sower, Stacia A, additional, Decatur, Wayne A, additional, Hall, Jeffrey A, additional, Amemiya, Chris T, additional, Saha, Nil R, additional, Buckley, Katherine M, additional, Rast, Jonathan P, additional, Das, Sabyasachi, additional, Hirano, Masayuki, additional, McCurley, Nathanael, additional, Guo, Peng, additional, Rohner, Nicolas, additional, Tabin, Clifford J, additional, Piccinelli, Paul, additional, Elgar, Greg, additional, Ruffier, Magali, additional, Aken, Bronwen L, additional, Searle, Stephen M J, additional, Muffato, Matthieu, additional, Pignatelli, Miguel, additional, Herrero, Javier, additional, Jones, Matthew, additional, Brown, C Titus, additional, Chung-Davidson, Yu-Wen, additional, Nanlohy, Kaben G, additional, Libants, Scot V, additional, Yeh, Chu-Yin, additional, McCauley, David W, additional, Langeland, James A, additional, Pancer, Zeev, additional, Fritzsch, Bernd, additional, de Jong, Pieter J, additional, Zhu, Baoli, additional, Fulton, Lucinda L, additional, Theising, Brenda, additional, Flicek, Paul, additional, Bronner, Marianne E, additional, Warren, Wesley C, additional, Clifton, Sandra W, additional, Wilson, Richard K, additional, and Li, Weiming, additional
Published: 2013
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42. The genomic landscape of hypodiploid acute lymphoblastic leukemia

Author: Holmfeldt, Linda, primary, Wei, Lei, additional, Diaz-Flores, Ernesto, additional, Walsh, Michael, additional, Zhang, Jinghui, additional, Ding, Li, additional, Payne-Turner, Debbie, additional, Churchman, Michelle, additional, Andersson, Anna, additional, Chen, Shann-Ching, additional, McCastlain, Kelly, additional, Becksfort, Jared, additional, Ma, Jing, additional, Wu, Gang, additional, Patel, Samir N, additional, Heatley, Susan L, additional, Phillips, Letha A, additional, Song, Guangchun, additional, Easton, John, additional, Parker, Matthew, additional, Chen, Xiang, additional, Rusch, Michael, additional, Boggs, Kristy, additional, Vadodaria, Bhavin, additional, Hedlund, Erin, additional, Drenberg, Christina, additional, Baker, Sharyn, additional, Pei, Deqing, additional, Cheng, Cheng, additional, Huether, Robert, additional, Lu, Charles, additional, Fulton, Robert S, additional, Fulton, Lucinda L, additional, Tabib, Yashodhan, additional, Dooling, David J, additional, Ochoa, Kerri, additional, Minden, Mark, additional, Lewis, Ian D, additional, To, L Bik, additional, Marlton, Paula, additional, Roberts, Andrew W, additional, Raca, Gordana, additional, Stock, Wendy, additional, Neale, Geoffrey, additional, Drexler, Hans G, additional, Dickins, Ross A, additional, Ellison, David W, additional, Shurtleff, Sheila A, additional, Pui, Ching-Hon, additional, Ribeiro, Raul C, additional, Devidas, Meenakshi, additional, Carroll, Andrew J, additional, Heerema, Nyla A, additional, Wood, Brent, additional, Borowitz, Michael J, additional, Gastier-Foster, Julie M, additional, Raimondi, Susana C, additional, Mardis, Elaine R, additional, Wilson, Richard K, additional, Downing, James R, additional, Hunger, Stephen P, additional, Loh, Mignon L, additional, and Mullighan, Charles G, additional
Published: 2013
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43. Somatic neurofibromatosis type 1 (NF1) inactivation characterizes NF1-associated pilocytic astrocytoma

Author: Gutmann, David H., primary, McLellan, Michael D., additional, Hussain, Ibrahim, additional, Wallis, John W., additional, Fulton, Lucinda L., additional, Fulton, Robert S., additional, Magrini, Vincent, additional, Demeter, Ryan, additional, Wylie, Todd, additional, Kandoth, Cyriac, additional, Leonard, Jeffrey R., additional, Guha, Abhijit, additional, Miller, Christopher A., additional, Ding, Li, additional, and Mardis, Elaine R., additional
Published: 2012
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44. Abstract LB-423: Whole genome comparisons of pre- and post- aromatase inhibitor treatment in estrogen receptor positive breast cancer

Author: Ellis, Matthew J., primary, Li, Ding, additional, Shen, Dong, additional, Luo, Jingqin, additional, Suman, Vera J., additional, Wallis, John W., additional, Van Tine, Brian A., additional, Hoog, Jeremy, additional, Crowder, Robert J., additional, Snider, Jacqueline E., additional, Ballman, Karla, additional, Chen, Ken, additional, Koboldt, Daniel C., additional, Schierding, William S., additional, McMichael, Joshua F., additional, Miller, Christopher A., additional, Kandoth, Cyriac, additional, Lu, Charles, additional, Harris, Christopher C., additional, McLellan, Michael D., additional, Wendl, Michael C., additional, DeSchryver, Katherine, additional, Allred, D. Craig, additional, Esserman, Laura, additional, Unzeitig, Gary, additional, Margenthaler, Julie, additional, Babiera, G.V., additional, Marcom, P. Kelly, additional, Guenther, J.M., additional, Leitch, Marilyn, additional, Hunt, Kelly, additional, Olson, John, additional, Tao, Yu, additional, Fulton, Lucinda L., additional, Fulton, Robert S., additional, Harrison, Michelle, additional, Oberkfell, Ben, additional, Du, Feiyu, additional, Demeter, Ryan, additional, Griffith, Malachi, additional, Vickery, Tammi L., additional, McDonald, Sandra A., additional, Watson, Mark, additional, Dooling, David J., additional, Ota, David, additional, Chang, Li-Wei, additional, Bose, Ron, additional, Ley, Timothy J., additional, Wilson, Richard K., additional, and Mardis, Elaine R., additional
Published: 2012
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45. De Novo Gene Disruptions in Children on the Autistic Spectrum

Author: Iossifov, Ivan, primary, Ronemus, Michael, additional, Levy, Dan, additional, Wang, Zihua, additional, Hakker, Inessa, additional, Rosenbaum, Julie, additional, Yamrom, Boris, additional, Lee, Yoon-ha, additional, Narzisi, Giuseppe, additional, Leotta, Anthony, additional, Kendall, Jude, additional, Grabowska, Ewa, additional, Ma, Beicong, additional, Marks, Steven, additional, Rodgers, Linda, additional, Stepansky, Asya, additional, Troge, Jennifer, additional, Andrews, Peter, additional, Bekritsky, Mitchell, additional, Pradhan, Kith, additional, Ghiban, Elena, additional, Kramer, Melissa, additional, Parla, Jennifer, additional, Demeter, Ryan, additional, Fulton, Lucinda L., additional, Fulton, Robert S., additional, Magrini, Vincent J., additional, Ye, Kenny, additional, Darnell, Jennifer C., additional, Darnell, Robert B., additional, Mardis, Elaine R., additional, Wilson, Richard K., additional, Schatz, Michael C., additional, McCombie, W. Richard, additional, and Wigler, Michael, additional
Published: 2012
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46. Whole Genome Sequences of Three Treponema pallidum ssp. pertenue Strains: Yaws and Syphilis Treponemes Differ in Less than 0.2% of the Genome Sequence

Author: Čejková, Darina, primary, Zobaníková, Marie, additional, Chen, Lei, additional, Pospíšilová, Petra, additional, Strouhal, Michal, additional, Qin, Xiang, additional, Mikalová, Lenka, additional, Norris, Steven J., additional, Muzny, Donna M., additional, Gibbs, Richard A., additional, Fulton, Lucinda L., additional, Sodergren, Erica, additional, Weinstock, George M., additional, and Šmajs, David, additional
Published: 2012
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47. Mutational Analysis of EGFR and Related Signaling Pathway Genes in Lung Adenocarcinomas Identifies a Novel Somatic Kinase Domain Mutation in FGFR4

Author: Marks, Jenifer L., primary, McLellan, Michael D., additional, Zakowski, Maureen F., additional, Lash, Alex E., additional, Kasai, Yumi, additional, Broderick, Stephen, additional, Sarkaria, Inderpal S., additional, Pham, DuyKhanh, additional, Singh, Bhuvanesh, additional, Miner, Tracie L., additional, Fewell, Ginger A., additional, Fulton, Lucinda L., additional, Mardis, Elaine R., additional, Wilson, Richard K., additional, Kris, Mark G., additional, Rusch, Valerie W., additional, Varmus, Harold, additional, and Pao, William, additional
Published: 2007
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48. Genome remodelling in a basal-like breast cancer metastasis and xenograft.

Author: Li Ding, Ellis, Matthew J., Shunqiang Li, Larson, David E., Ken Chen, Wallis, John W., Harris, Christopher C., McLellan, Michael D., Fulton, Robert S., Fulton, Lucinda L., Abbott, Rachel M., Hoog, Jeremy, Dooling, David J., Koboldt, Daniel C., Schmidt, Heather, Kalicki, Joelle, Qunyuan Zhang, Lei Chen, Ling Lin, and Wendl, Michael C.
Subjects: BREAST cancer, GENOMES, BASAL cell carcinoma, XENOGRAFTS, METASTASIS, CANCER invasiveness
Abstract: Massively parallel DNA sequencing technologies provide an unprecedented ability to screen entire genomes for genetic changes associated with tumour progression. Here we describe the genomic analyses of four DNA samples from an African-American patient with basal-like breast cancer: peripheral blood, the primary tumour, a brain metastasis and a xenograft derived from the primary tumour. The metastasis contained two de novo mutations and a large deletion not present in the primary tumour, and was significantly enriched for 20 shared mutations. The xenograft retained all primary tumour mutations and displayed a mutation enrichment pattern that resembled the metastasis. Two overlapping large deletions, encompassing CTNNA1, were present in all three tumour samples. The differential mutation frequencies and structural variation patterns in metastasis and xenograft compared with the primary tumour indicate that secondary tumours may arise from a minority of cells within the primary tumour. [ABSTRACT FROM AUTHOR]
Published: 2010
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49. Somatic neurofibromatosis type 1 (NF1) inactivation characterizes NF1-associated pilocytic astrocytoma.

Author: Gutmann, David H., McLellan, Michael D., Hussain, Ibrahim, Wallis, John W., Fulton, Lucinda L., Fulton, Robert S., Magrini, Vincent, Demeter, Ryan, Wylie, Todd, Kandoth, Cyriac, Leonard, Jeffrey R., Guha, Abhijit, Miller, Christopher A., Li Ding, and Mardis, Elaine R.
Subjects: *ASTROCYTOMAS, *NEUROFIBROMATOSIS, *BRAIN tumors, *GENETICS of disease susceptibility, *GERM cell tumors
Abstract: Low-grade brain tumors (pilocytic astrocytomas) arising in the neurofibromatosis type 1 (NF1) inherited cancer predisposition syndrome are hypothesized to result from a combination of germline and acquired somatic NF1 tumor suppressor gene mutations. However, genetically engineered mice (GEM) in which mono-allelic germline Nf1 gene loss is coupled with bi-allelic somatic (glial progenitor cell) Nf1 gene inactivation develop brain tumors that do not fully recapitulate the neuropathological features of the human condition. These observations raise the intriguing possibility that, while loss of neurofibromin function is necessary for NF1-associated low-grade astrocytoma development, additional genetic changes may be required for full penetrance of the human brain tumor phenotype. To identify these potential cooperating genetic mutations, we performed whole-genome sequencing (WGS) analysis of three NF1-associated pilocytic astrocytoma (PA) tumors. We found that the mechanism of somatic NF1 loss was different in each tumor (frameshift mutation, loss of heterozygosity, and methylation). In addition, tumor purity analysis revealed that these tumors had a high proportion of stromal cells, such that only 50%-60% of cells in the tumor mass exhibited somatic NF1 loss. Importantly, we identified no additional recurrent pathogenic somatic mutations, supporting a model in which neuroglial progenitor cell NF1 loss is likely sufficient for PA formation in cooperation with a proper stromal environment. [ABSTRACT FROM AUTHOR]
Published: 2013
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50. The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma.

Author: Wu G, Diaz AK, Paugh BS, Rankin SL, Ju B, Li Y, Zhu X, Qu C, Chen X, Zhang J, Easton J, Edmonson M, Ma X, Lu C, Nagahawatte P, Hedlund E, Rusch M, Pounds S, Lin T, Onar-Thomas A, Huether R, Kriwacki R, Parker M, Gupta P, Becksfort J, Wei L, Mulder HL, Boggs K, Vadodaria B, Yergeau D, Russell JC, Ochoa K, Fulton RS, Fulton LL, Jones C, Boop FA, Broniscer A, Wetmore C, Gajjar A, Ding L, Mardis ER, Wilson RK, Taylor MR, Downing JR, Ellison DW, Zhang J, and Baker SJ
Subjects: Animals, Child, Cohort Studies, Computational Biology, Gene Expression Profiling, Gene Fusion genetics, Humans, Immunoblotting, Immunohistochemistry, Microarray Analysis, Receptor, trkA genetics, Receptor, trkB genetics, Receptor, trkC genetics, Reverse Transcriptase Polymerase Chain Reaction, Sequence Analysis, DNA, Statistics, Nonparametric, Zebrafish, Activin Receptors, Type I genetics, Brain Stem Neoplasms genetics, Glioma genetics, Signal Transduction genetics
Abstract: Pediatric high-grade glioma (HGG) is a devastating disease with a less than 20% survival rate 2 years after diagnosis. We analyzed 127 pediatric HGGs, including diffuse intrinsic pontine gliomas (DIPGs) and non-brainstem HGGs (NBS-HGGs), by whole-genome, whole-exome and/or transcriptome sequencing. We identified recurrent somatic mutations in ACVR1 exclusively in DIPGs (32%), in addition to previously reported frequent somatic mutations in histone H3 genes, TP53 and ATRX, in both DIPGs and NBS-HGGs. Structural variants generating fusion genes were found in 47% of DIPGs and NBS-HGGs, with recurrent fusions involving the neurotrophin receptor genes NTRK1, NTRK2 and NTRK3 in 40% of NBS-HGGs in infants. Mutations targeting receptor tyrosine kinase-RAS-PI3K signaling, histone modification or chromatin remodeling, and cell cycle regulation were found in 68%, 73% and 59% of pediatric HGGs, respectively, including in DIPGs and NBS-HGGs. This comprehensive analysis provides insights into the unique and shared pathways driving pediatric HGG within and outside the brainstem.
Published: 2014
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