المؤلفون: Morin, R.D., Mendez-Lago, M., Mungall, A.J., Goya, R., Mungall, K.L., Corbett, R.D., Johnson, N.A., Severson, T.M., Chiu, R., Field, M., Jackman, S., Krzywinski, M., Scott, D.W., Trinh, D.L., Tamura-Wells, J., Li, S., Firme, M.R., Rogic, S., Griffith, M., Chan, S., Yakovenko, O., Meyer, I.M., Zhao, E.Y., Smailus, D., Moksa, M., Chittaranjan, S., Rimsza, L., Brooks-Wilson, A., Spinelli, J.J., Ben-Neriah, S., Meissner, B., Woolcock, B., Boyle, M., McDonald, H., Tam, A., Zhao, Y., Delaney, A., Zeng, T., Tse, K., Butterfield, Y., Birol, I., Holt, R., Schein, J., Horsman, D.E., Moore, R., Jones, S.J.M., Connors, J.M., Hirst, M., Gascoyne, R.D., Marra, M.A.

مصطلحات موضوعية: Cancer Research

الوصف: Follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) are the two most common non-Hodgkin lymphomas (NHLs). Here we sequenced tumour and matched normal DNA from 13 DLBCL cases and one FL case to identify genes with mutations in B-cell NHL. We analysed RNA-seq data from these and another 113 NHLs to identify genes with candidate mutations, and then re-sequenced tumour and matched normal DNA from these cases to confirm 109 genes with multiple somatic mutations. Genes with roles in histone modification were frequent targets of somatic mutation. For example, 32% of DLBCL and 89% of FL cases had somatic mutations in MLL2, which encodes a histone methyltransferase, and 11.4% and 13.4% of DLBCL and FL cases, respectively, had mutations in MEF2B, a calcium-regulated gene that cooperates with CREBBP and EP300 in acetylating histones. Our analysis suggests a previously unappreciated disruption of chromatin biology in lymphomagenesis.

العلاقة: Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma. Morin, R.D. and Mendez-Lago, M. and Mungall, A.J. and Goya, R. and Mungall, K.L. and Corbett, R.D. and Johnson, N.A. and Severson, T.M. and Chiu, R. and Field, M. and Jackman, S. and Krzywinski, M. and Scott, D.W. and Trinh, D.L. and Tamura-Wells, J. and Li, S. and Firme, M.R. and Rogic, S. and Griffith, M. and Chan, S. and Yakovenko, O. and Meyer, I.M. and Zhao, E.Y. and Smailus, D. and Moksa, M. and Chittaranjan, S. and Rimsza, L. and Brooks-Wilson, A. and Spinelli, J.J. and Ben-Neriah, S. and Meissner, B. and Woolcock, B. and Boyle, M. and McDonald, H. and Tam, A. and Zhao, Y. and Delaney, A. and Zeng, T. and Tse, K. and Butterfield, Y. and Birol, I. and Holt, R. and Schein, J. and Horsman, D.E. and Moore, R. and Jones, S.J.M. and Connors, J.M. and Hirst, M. and Gascoyne, R.D. and Marra, M.A. Nature 476 (7360): 298-303. 18 August 2011

الإتاحة: https://doi.org/10.1038/nature10351Test
http://edoc.mdc-berlin.de/14204Test/
https://edoc.mdc-berlin.de/14204Test/

المؤلفون: Robertson, G., Schein, J., Chiu, R., Corbett, R., Field, M., Jackman, S., Mungall, K., Lee, S., Okada, H., Qian, J., Griffith, M., Raymond, A., Thiessen, N., Cezard, T., Butterfield, Y., Newsome, R., Chan, S., She, R., Varhol, Richard, Kamoh, B., Prabhu, A., Tam, A., Zhao, Y., Moore, R., Hirst, M., Marra, M., Jones, S., Hoodless, P., Birol, I.

الوصف: We describe Trans-ABySS, a de novo short-read transcriptome assembly and analysis pipeline that addresses variation in local read densities by assembling read substrings with varying stringencies and then merging the resulting contigs before analysis. Analyzing 7.4 gigabases of 50-base-pair paired-end Illumina reads from an adult mouse liver poly(A) RNA library, we identified known, new and alternative structures in expressed transcripts, and achieved high sensitivity and specificity relative to reference-based assembly methods. © 2010 Nature America, Inc. All rights reserved.

وصف الملف: restricted

العلاقة: http://hdl.handle.net/20.500.11937/16548Test

الإتاحة: https://doi.org/20.500.11937/16548Test
https://doi.org/10.1038/nmeth.1517Test
https://hdl.handle.net/20.500.11937/16548Test

المؤلفون: Morin, R. D., Chang, E., Petrescu, A., Liao, N., Kirkpatrick, R., Griffith, M., Butterfield, Y., Stott, J., Barber, S., Babakaiff, R., Matsuo, C., Wong, D., Yang, G., Smailus, D., Brown-John, M., Mayo, M., Beland, J., Gibson, S., Olson, T., Tsai, M., Featherstone, R., Chand, S., Siddiqui, A., Jang, W., Lee, E., Klein, S., Prange, C., Myers, R. M., Green, E. D., Wagner, L., Gerhard, D., Marra, M., Jones, S. M., Holt, R.

المساهمون: United States. Department of Energy.

المصدر: Journal Name: Genome Research , vol. 16, no. 6, June 1, 2006, pp. 796-803

مصطلحات موضوعية: Genes, Dna Sequencing, Cloning, Frogs, 59 Basic Biological Sciences

الوصف: Sequencing of full-insert clones from full-length cDNA libraries from both Xenopus laevis and Xenopus tropicalis has been ongoing as part of the Xenopus Gene Collection initiative. Here we present an analysis of 10967 clones (8049 from X. laevis and 2918 from X. tropicalis). The clone set contains 2013 orthologs between X. laevis and X. tropicalis as well as 1795 paralog pairs within X. laevis. 1199 are in-paralogs, believed to have resulted from an allotetraploidization event approximately 30 million years ago, and the remaining 546 are likely out-paralogs that have resulted from more ancient gene duplications, prior to the divergence between the two species. We do not detect any evidence for positive selection by the Yang and Nielsen maximum likelihood method of approximating d{sub N}/d{sub S}. However, d{sub N}/d{sub S} for X. laevis in-paralogs is elevated relative to X. tropicalis orthologs. This difference is highly significant, and indicates an overall relaxation of selective pressures on duplicated gene pairs. Within both groups of paralogs, we found evidence of subfunctionalization, manifested as differential expression of paralogous genes among tissues, as measured by EST information from public resources. We have observed, as expected, a higher instance of subfunctionalization in out-paralogs relative to in-paralogs.

وصف الملف: 31 p.; ill.; Text

العلاقة: rep-no: UCRL-JRNL-216808; grantno: W-7405-ENG-48; osti: 889991; https://digital.library.unt.edu/ark:/67531/metadc875300Test/; ark: ark:/67531/metadc875300

الإتاحة: https://digital.library.unt.edu/ark:/67531/metadc875300Test/

المؤلفون: Gerhard, D. S., Wagner, L., Feingold, E. A., Shenmen, C. M., Grouse, L. H., Schuler, G., Klein, S. L., Old, S., Rasooly, R., Good, P., Guyer, M., Peck, A. M., Derge, J. G., Lipman, D., Collins, F. S., Jang, W., Sherry, S., Feolo, M., Misquitta, L., Lee, E., Rotmistrovsky, K., Greenhut, S. F., Schaefer, C. F., Buetow, K. H., Bonner, T. I., Haussler, D., Kent, J., Diekhans, M., Furey, T., Brent, M., Prange, C., Schreiber, K., Shapiro, N., Bhat, N. K., Hopkins, R. F., Hsie, F., Driscoll, T., Soares, M. B., Bonaldo, M. F., Casavant, T. L., Scheetz, T. E., Brownstein, M. J., Usdin, T. B., Toshiyuki, S., Carninci, P., Piao, Y., Dudekula, D. B., Ko, M. S. H., Kawakami, K., Suzuki, Y., Sugano, S., Gruber, C. E., Smith, M. R., Simmons, B., Moore, T., Waterman, R., Johnson, S. L., Ruan, Y., Lin Wei, C., Mathavan, S., Gunaratne, P. H., Wu, J., Garcia, A. M., Hulyk, S. W., Fuh, E., Yuan, Y., Sneed, A., Kowis, C., Hodgson, A., Muzny, D. M., John McPherson, Gibbs, R. A., Fahey, J., Helton, E., Ketteman, M., Madan, A., Rodrigues, S., Sanchez, A., Whiting, M., Young, A. C., Wetherby, K. D., Granite, S. J., Kwong, P. N., Brinkley, C. P., Pearson, R. L., Bouffard, G. G., Blakesly, R. W., Green, E. D., Dickson, M. C., Rodriguez, A. C., Grimwood, J., Schmutz, J., Myers, R. M., Butterfield, Y. S. N., Griffith, M., Griffith, O. L., Krzywinski, M. I., Liao, N., Morrin, R., Palmquist, D., Petrescu, A. S., Skalska, U., Smailus, D. E., Stott, J. M., Schnerch, A., Schein, J. E., Jones, S. J. M., Holt, R. A., Baross, A., Marra, M. A., Clifton, S., Makowski, K. A., Bosak, S., Malek, J.

المصدر: Scopus-Elsevier

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=dedup_wf_001::2992dd2229400fd5e934349f07b001e5Test
http://www.scopus.com/inward/record.url?eid=2-s2.0-7444262496&partnerID=MN8TOARSTest

المؤلفون: Morin, R. D., Chang, E., Petrescu, A., Liao, N., Griffith, M., Chow, W., Kirkpatrick, R., Butterfield, Y. S., Young, A. C., Stott, J., Barber, S., Babakaiff, R., Dickson, M. C., Matsuo, C., Wong, D., Yang, G. S., Smailus, D. E., Wetherby, K. D., Kwong, P. N., Grimwood, J., Brinkley Iii, C. P., Brown-John, M., Reddix-Dugue, N. D., Mayo, M., Schmutz, J., Beland, J., Park, M., Gibson, S., Olson, T., Bouffard, G. G., Tsai, M., Featherstone, R., Chand, S., Siddiqui, A. S., Jang, W., Lee, E., Klein, S. L., Blakesley, R. W., Zeeberg, B. R., Narasimhan, S., John Weinstein, Pennacchio, C. P., Myers, R. M., Green, E. D., Wagner, L., Gerhard, D. S., Marra, M. A., Jones, S. J. M., Holt, R. A.

المصدر: Scopus-Elsevier

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=dedup_wf_001::7579e7cc17c8ca94d7eac8e8b385451bTest
http://www.scopus.com/inward/record.url?eid=2-s2.0-33745589836&partnerID=MN8TOARSTest

المؤلفون: Baross, Á, Butterfield, Y. S. N., Coughlin, S. M., Zeng, T., Griffith, M., Obi Griffith, Petrescu, A. S., Smailus, D. E., Khattra, J., Mcdonald, H. L., Mckay, S. J., Moksa, M., Holt, R. A., Marra, M. A.

المصدر: Scopus-Elsevier

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=dedup_wf_001::3f31516620ff849b4f2693d309afe871Test
http://www.scopus.com/inward/record.url?eid=2-s2.0-7444226322&partnerID=MN8TOARSTest

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

المساهمون: Brat D.J., Verhaak R.G.W., Aldape K.D., Yung W.K.A., Salama S.R., Cooper L.A.D., Rheinbay E., Miller C.R., Vitucci M., Morozova O., Robertson A.G., Noushmehr H., Laird P.W., Cherniack A.D., Akbani R., Huse J.T., Ciriello G., Poisson L.M., Barnholtz-Sloan J.S., Berger M.S., Brennan C., Colen R.R., Colman H., Flanders A.E., Giannini C., Grifford M., Iavarone A., Jain R., Joseph I., Kim J., Kasaian K., Mikkelsen T., Murray B.A., O'Neill B.P., Pachter L., Parsons D.W., Sougnez C., Sulman E.P., Vandenberg S.R., Van Meir E.G., Von Deimling A., Zhang H., Crain D., Lau K., Mallery D., Morris S., Paulauskis J., Penny R., Shelton T., Sherman M., Yena P., Black A., Bowen J., Dicostanzo K., Gastier-Foster J., Leraas K.M., Lichtenberg T.M., Pierson C.R., Ramirez N.C., Taylor C., Weaver S., Wise L., Zmuda E., Davidsen T., Demchok J.A., Eley G., Ferguson M.L., Hutter C.M., Shaw K.R.M., Ozenberger B.A., Sheth M., Sofia H.J., Tarnuzzer R., Wang Z., Yang L., Zenklusen J.C., Ayala B., Baboud J., Chudamani S., Jensen M.A., Liu J., Pihl T., Raman R., Wan Y., Wu Y., Ally A., Auman J.T., Balasundaram M., Balu S., Baylin S.B., Beroukhim R., Bootwalla M.S., Bowlby R., Bristow C.A., Brooks D., Butterfield Y., Carlsen R., Carter S., Chin L., Chu A., Chuah E., Cibulskis K., Clarke A., Coetzee S.G., Dhalla N., Fennell T., Fisher S., Gabriel S., Getz G., Gibbs R., Guin R., Hadjipanayis A., Hayes D.N., Hinoue T., Hoadley K., Holt R.A., Hoyle A.P., Jefferys S.R., Jones S., Jones C.D., Kucherlapati R., Lai P.H., Lander E., Lee S., Lichtenstein L., Ma Y., Maglinte D.T., Mahadeshwar H.S., Marra M.A., Mayo M., Meng S., Meyerson M.L., Mieczkowski P.A., Moore R.A., Mose L.E., Mungall A.J., Pantazi A., Parfenov M., Park P.J., Parker J.S., Perou C.M., Protopopov A., Ren X., Roach J., Sabedot T.S., Schein J., Schumacher S.E., Seidman J.G., Seth S., Shen H., Simons J.V., Sipahimalani P., Soloway M.G., Song X., Sun H., Tabak B., Tam A., Tan D., Tang J., Thiessen N., Triche T., Van Den Berg D.J., Veluvolu U., Waring S., Weisenberger D.J., Wilkerson M.D., Wong T., Wu J., Xi L., Xu A.W., Zack T.I., Zhang J., Aksoy B.A., Arachchi H., Benz C., Bernard B., Carlin D., Cho J., DiCara D., Frazer S., Fuller G.N., Gao J., Gehlenborg N., Haussler D., Heiman D.I., Iype L., Jacobsen A., Ju Z., Katzman S., Kim H., Knijnenburg T., Kreisberg R.B., Lawrence M.S., Lee W., Leinonen K., Lin P., Ling S., Liu W., Liu Y., Lu Y., Mills G., Ng S., Noble M.S., Paull E., Rao A., Reynolds S., Saksena G., Sanborn Z., Sander C., Schultz N., Senbabaoglu Y., Shen R., Shmulevich I., Sinha R., Stuart J., Sumer S.O., Sun Y., Tasman N., Taylor B.S., Voet D., Weinhold N., Weinstein J.N., Yang D., Yoshihara K., Zheng S., Zhang W., Zou L., Abel T., Sadeghi S., Cohen M.L., Eschbacher J., Hattab E.M., Raghunathan A., Schniederjan M.J., Aziz D., Barnett G., Barrett W., Bigner D.D., Boice L., Brewer C., Calatozzolo C., Campos B., Carlotti C.G., Chan T.A., Cuppini L., Curley E., Cuzzubbo S., Devine K., DiMeco F., Duell R., Elder J.B., Fehrenbach A., Finocchiaro G., Friedman W., Fulop J., Gardner J., Hermes B., Herold-Mende C., Jungk C., Kendler A., Lehman N.L., Lipp E., Liu O., Mandt R., McGraw M., Mclendon R., McPherson C., Neder L., Nguyen P., Noss A., Nunziata R., Ostrom Q.T., Palmer C., Perin A., Pollo B., Potapov A., Potapova O., Rathmell W.K., Rotin D., Scarpace L., Schilero C., Senecal K., Shimmel K., Shurkhay V., Sifri S., Singh R., Sloan A.E., Smolenski K., Staugaitis S.M., Steele R., Thorne L., Tirapelli D.P.C., Unterberg A., Vallurupalli M., Wang Y., Warnick R., Williams F., Wolinsky Y., Bell S., Rosenberg M., Stewart C., Huang F., Grimsby J.L., Radenbaugh A.J.

المصدر: Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual)
Universidade de São Paulo (USP)
instacron:USP

مصطلحات موضوعية: Adult, Male, Pathology, medicine.medical_specialty, IDH1, Adolescent, Kaplan-Meier Estimate, 1p/19q Codeletion, Biology, Article, Glioma, Molecular genetics, Grade II Glioma, medicine, Cluster Analysis, Humans, neoplasms, Exome, ATRX, Proportional Hazards Models, Aged, Cluster Analysi, DNA, Neoplasm, Sequence Analysis, DNA, General Medicine, Middle Aged, Genes, p53, medicine.disease, Chromosomes, Human, Pair 1, Mutation, Proportional Hazards Model, Cancer research, GLIOMA, Female, Oligodendroglioma, Neoplasm Grading, Glioblastoma, Chromosomes, Human, Pair 19, Human, Signal Transduction

الوصف: BACKGROUND: Diffuse low-grade and intermediate-grade gliomas (which together make up the lower-grade gliomas, World Health Organization grades II and III) have highly variable clinical behavior that is not adequately predicted on the basis of histologic class. Some are indolent; others quickly progress to glioblastoma. The uncertainty is compounded by interobserver variability in histologic diagnosis. Mutations in IDH, TP53, and ATRX and codeletion of chromosome arms 1p and 19q (1p/19q codeletion) have been implicated as clinically relevant markers of lower-grade gliomas. METHODS: We performed genomewide analyses of 293 lower-grade gliomas from adults, incorporating exome sequence, DNA copy number, DNA methylation, messenger RNA expression, microRNA expression, and targeted protein expression. These data were integrated and tested for correlation with clinical outcomes. RESULTS: Unsupervised clustering of mutations and data from RNA, DNA-copy-number, and DNA-methylation platforms uncovered concordant classification of three robust, nonoverlapping, prognostically significant subtypes of lower-grade glioma that were captured more accurately by IDH, 1p/19q, and TP53 status than by histologic class. Patients who had lower-grade gliomas with an IDH mutation and 1p/19q codeletion had the most favorable clinical outcomes. Their gliomas harbored mutations in CIC, FUBP1, NOTCH1, and the TERT promoter. Nearly all lower-grade gliomas with IDH mutations and no 1p/19q codeletion had mutations in TP53 (94%) and ATRX inactivation (86%). The large majority of lower-grade gliomas without an IDH mutation had genomic aberrations and clinical behavior strikingly similar to those found in primary glioblastoma. CONCLUSIONS: The integration of genomewide data from multiple platforms delineated three molecular classes of lower-grade gliomas that were more concordant with IDH, 1p/19q, and TP53 status than with histologic class. Lower-grade gliomas with an IDH mutation either had 1p/19q codeletion or carried a TP53 mutation. Most lower-grade gliomas without an IDH mutation were molecularly and clinically similar to glioblastoma. (Funded by the National Institutes of Health.)

وصف الملف: application/pdf; STAMPA

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6678eeed8340c293a6651ee6ab2d2c5bTest
https://doi.org/10.1056/nejmoa1402121Test