Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas.

@article{Brat2015ComprehensiveIG,
  title={Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas.},
  author={Daniel J. Brat and Roel G. W. Verhaak and Kenneth D. Aldape and W. K. Alfred Yung and Sofie R. Salama and Lee A. D. Cooper and Esther Rheinbay and C. Ryan Miller and Mark Vitucci and Olena Morozova and A. Gordon Robertson and Houtan Noushmehr and Peter W. Laird and Andrew D. Cherniack and Rehan Akbani and Jason T. Huse and Giovanni Domenico Ciriello and Laila M. Poisson and Jill S. Barnholtz-Sloan and Mitchel S. Berger and Cameron W. Brennan and Rivka R. Colen and Howard Colman and Adam E. Flanders and Caterina Giannini and Mia Grifford and Antonio Iavarone and Rajan Jain and Isaac Charles Joseph and Jaegil Kim and Katayoon Kasaian and Tom Mikkelsen and Bradley A. Murray and Brian P. O'neill and Lior Pachter and Donald W. Parsons and Carrie Sougnez and Erik P. Sulman and Scott R. Vandenberg and Erwin G. Van Meir and Andreas von Deimling and Hailei Zhang and Daniel Crain and Kevin R Lau and David W Mallery and Scott Morris and Joseph D. Paulauskis and Robert J. Penny and Troy Shelton and Mark E. Sherman and Peggy Yena and Aaron D. Black and Jay Bowen and Katie Dicostanzo and Julie M. Gastier-Foster and Kristen Leraas and Tara M. Lichtenberg and Christopher R. Pierson and Nilsa C. Ramirez and Cynthia Taylor and Stephanie Weaver and Lisa Wise and E J Zmuda and Tanja Davidsen and John A. Demchok and Greg Eley and Martin L Ferguson and Carolyn Hutter and Kenna R. Mills Shaw and Bradley A Ozenberger and Margi Sheth and Heidi J. Sofia and Roy W. Tarnuzzer and Zhining Wang and Liming Yang and Jean Claude Zenklusen and Brenda Ayala and Julien Baboud and Sudha Chudamani and Mark A. Jensen and Jia Liu and Todd Pihl and Rohini Raman and Yunhu Wan and Ye Wu and Adrian Ally and James T. Auman and Miruna Balasundaram and Saianand Balu and Stephen B. Baylin and Rameen Beroukhim and Moiz S. Bootwalla and Reanne Bowlby and Christopher Aaron Bristow and Denise Brooks and Yaron S. N. Butterfield and Rebecca Carlsen and Scott L. Carter and Lynda Chin and Andy Chu and Eric Chuah and Kristian Cibulskis and Amanda Clarke and Simon G. Coetzee and Noreen Dhalla and Tim Fennell and Sheila A Fisher and S. Gabriel and Gad Getz and Richard A. Gibbs and Ranabir Guin and Angela Hadjipanayis and David Neil Hayes and Toshinori Hinoue and Katherine A. Hoadley and Robert A. Holt and Alan Hoyle and Stuart R. Jefferys and Steven J. M. Jones and Corbin D. Jones and Raju Kucherlapati and Phillip H. Lai and Eric S. Lander and Semin Lee and Lee T Lichtenstein and Yussanne Ma and Dennis T. Maglinte and Harshad S. Mahadeshwar and Marco A. Marra and Michael Mayo and Shaowu Meng and Matthew L Meyerson and Piotr A. Mieczkowski and Richard A. Moore and Lisle E. Mose and Andrew J. Mungall and Angeliki Pantazi and Michael G Parfenov and Peter J. Park and Joel S. Parker and Charles M. Perou and Alexei Protopopov and Xiaojia Ren and Jeffrey M. Roach and Tha{\'i}s S. Sabedot and Jacqueline E. Schein and Steven E Schumacher and Jonathan G. Seidman and Sahil Seth and Hui Shen and Janae V. Simons and Payal Sipahimalani and Matthew G. Soloway and Xingzhi Song and Huandong Sun and Barbara Tabak and Angela Tam and Donghui Tan and Jiabin Tang and Nina Thiessen and Timothy J. Triche and David J. Van Den Berg and Umadevi Veluvolu and Scot Michael Waring and Daniel J. Weisenberger and Matthew D. Wilkerson and Tina Wong and Junyuan Wu and Liu Xi and Andrew Wei Xu and Lixing Yang and T. Zack and Jianhua Zhang and B{\"u}lent Arman Aksoy and Harindra M. Arachchi and Christiane Benz and Brady Bernard and Daniel E. Carlin and Juok Cho and Danielle M. Dicara and Scott R. Frazer and Gregory N. Fuller and Jianjiong Gao and Nils Gehlenborg and David Haussler and David I. Heiman and Lisa E. Iype and Anders S. Jacobsen and Zhenlin Ju and Sol Katzman and Hoon Kim and Theo A. Knijnenburg and Richard Kreisberg and Michael S. Lawrence and William Lee and Kalle Leinonen and Pei Lin and Shiyun Ling and Wenbin Liu and YingChun Liu and Yuexin Liu and Yiling Lu and Gordon B. Mills and Sam Ng and Michael S. Noble and Evan O. Paull and Arvind U. K. Rao and Sheila M. Reynolds and Gordon Saksena and Zachary Sanborn and Chris Sander and Nikolaus D. Schultz and Yasin Şenbabaoğlu and Ronglai Shen and Ilya Shmulevich and Rileen Sinha and Josh M Stuart and Selcuk Onur Sumer and Yichao Sun and Natalie I. Tasman and Barry S. Taylor and Douglas Voet and Nils Weinhold and John N. Weinstein and Da Yang and Kosuke Yoshihara and Siyuan Zheng and Wei Zhang and Lihua Zou and Ty William Abel and Sara Sadeghi and Mark L. Cohen and Jennifer Eschbacher and Eyas M. Hattab and Aditya Raghunathan and Matthew J Schniederjan and Dina Aziz and Gene H. Barnett and Wendi Barrett and Darell D. Bigner and L. Peter Boice and Cathy Brewer and Chiara Calatozzolo and Benito Campos and Carlos Gilberto Carlotti and Timothy A. Chan and Lucia Cuppini and Erin E. Curley and Stefania Cuzzubbo and Karen Dragon Devine and Francesco DiMeco and Rebecca Duell and J. Bradley Elder and Ashley Fehrenbach and Gaetano Finocchiaro and William Friedman and Jordonna Fulop and Johanna Gardner and Beth Hermes and Christel Herold‐Mende and Christine Jungk and Ady Kendler and Norman L. Lehman and Eric S. Lipp and Ouida Liu and Randy Mandt and Mary McGraw and R L McLendon and Christopher M. McPherson and Luciano Neder and Phuong Linh Nguyen and Ardene Noss and Raffaele Nunziata and Quinn T. Ostrom and Cheryl A Palmer and Alessandro Perin and Bianca Pollo and Alexander A. Potapov and Olga Potapova and W. Rathmell and Daniil Rotin and Lisa M. Scarpace and Cathy Schilero and Kelly Senecal and Kristen Shimmel and Vsevolod A. Shurkhay and Suzanne Sifri and Rosy Singh and Andrew E. Sloan and Kathy Smolenski and Susan M. Staugaitis and Ruth Steele and Leigh B. Thorne and Daniela Tirapelli and Andreas W. Unterberg and Mahitha Vallurupalli and Yun Wang and Ronald E. Warnick and Felicia Williams and Yingli Wolinsky and Sue Bell and Mara W Rosenberg and Chip Stewart and Franklin W. Huang and Jonna Grimsby and Amie Radenbaugh and Jianan Zhang},
  journal={The New England journal of medicine},
  year={2015},
  volume={372 26},
  pages={
          2481-98
        }
}
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… 

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References

SHOWING 1-10 OF 62 REFERENCES

Integrated DNA methylation and copy-number profiling identify three clinically and biologically relevant groups of anaplastic glioma

It is suggested that anaplastic gliomas can be grouped by IDH and 1p/19q status into three molecular groups that show clear links to underlying biology and a significant association with clinical outcome in a prospective trial cohort.

Update on molecular findings, management and outcome in low-grade gliomas

Molecular marker assessment will, hopefully, improve the accuracy of tumor diagnosis and enhance the effectiveness of treatment to achieve improved patient outcomes.

Mutational landscape and clonal architecture in grade II and III gliomas

Mutations showed significant positive and negative correlations and a chronological hierarchy, as inferred from different allelic burdens among coexisting mutations, suggesting that there is functional interplay between the mutations that drive clonal selection.

Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas

Focusing on the therapeutically challenging diffuse LGGs, this study of 151 tumors has discovered genetic alterations and potential therapeutic targets across the entire range of pediatric L GGs and LGGNTs.

Molecular genetics of gliomas.

Diffusely infiltrating gliomas are the most common primary brain tumors and include astrocytomas, oligodendrogliomas, and oligoastrocytomas of grades II and III and glioblastoma (GBM), grade IV.

A survey of intragenic breakpoints in glioblastoma identifies a distinct subset associated with poor survival.

A previously underappreciated genomic mechanism of gene deregulation that can confer growth advantages on tumor cells and may generate cancer-specific vulnerabilities in subsets of GBM is uncovered.

Glioma Groups Based on 1p/19q, IDH, and TERT Promoter Mutations in Tumors.

The five glioma molecular groups had different ages at onset, overall survival, and associations with germline variants, which implies that they are characterized by distinct mechanisms of pathogenesis.

An Integrated Genomic Analysis of Human Glioblastoma Multiforme

Recurrent mutations in the active site of isocitrate dehydrogenase 1 (IDH1) occurred in a large fraction of young patients and in most patients with secondary GBMs and were associated with an increase in overall survival.

The genetic landscape of anaplastic astrocytoma

Anaplastic astrocytoma WHO grade III (A3) is a lethal brain tumor that often occurs in middle aged patients. Clinically, it is challenging to distinguish A3 from glioblastoma multiforme (GBM) WHO
...