The Somatic Genomic Landscape of Glioblastoma

Brennan, Cameron; Verhaak, Roel G.W.; McKenna, Aaron; Campos, Benito; Noushmehr, Houtan; Salama, Sofie R.; Zheng, Siyuan; Chakravarty, Debyani; Sanborn, J. Zachary; Berman, Samuel H.; Beroukhim, Rameen; Bernard, Brady; Wu, Chang Jiun; Genovese, Giannicola; Shmulevich, Ilya; Barnholtz‐Sloan, Jill S.; Zou, Lihua; Vegesna, Rahulsimham; Shukla, Sachet A.; Ciriello, Giovanni; Yung, W. K. Alfred; Zhang, Wei; Sougnez, Carrie; Mikkelsen, Tom; Aldape, Kenneth; Bigner, Darell D.; Meir, Erwin G. Van; Prados, Michael D.; Sloan, Andrew E.; Black, Keith L.; Eschbacher, Jennifer; Finocchiaro, Gaetano; Friedman, William E.; Andrews, David W.; Guha, Abhijit; Iacocca, Mary; O’Neill, Brian Patrick; Foltz, Greg; Myers, Jerome; Weisenberger, Daniel J.; Penny, Robert; Kucherlapati, Raju; Perou, Charles M.; Hayes, D. Neil; Gibbs, Richard A.; Marra, Marco; Mills, Gordon B.; Lander, Eric S.; Spellman, Paul T.; Wilson, Richard F.; Sander, Chris; Weinstein, John N.; Meyerson, Matthew; Gabriel, Stacey; Laird, Peter W.; Haussler, David; Getz, Gad; Chin, Lynda

doi:10.1016/j.cell.2014.04.004

Cited by 566 publications

(915 citation statements)

References 0 publications

Supporting

Mentioning

823

Contrasting

Unclassified

Order By: Relevance

“…In 2013, the same specimens were analysed with next-generation sequencing (NGS) and another 337 specimens were added, ending up with 543 tumours 11. Seventy-one significantly mutated genes (SMGs) were found, which many of them corresponded with previous findings.…”

Section: Methodsmentioning

confidence: 92%

See 1 more Smart Citation

Hallmarks of glioblastoma: a systematic review

2016

View full text Add to dashboard Cite

Despite decades of intense research, the complex biology of glioblastoma (GBM) is not completely understood. Progression-free survival and overall survival have remained unchanged since the implementation of the STUPP regimen in 2005 with concomitant radio-/chemotherapy and adjuvant chemotherapy with temozolomide.In the context of Hanahan and Weinberg's six hallmarks and two emerging hallmarks of cancer, we discuss up-to-date status and recent research in the biology of GBM. We discuss the clinical impact of the research results with the most promising being in the hallmarks ‘enabling replicative immortality’, ‘inducing angiogenesis’, ‘reprogramming cellular energetics’ and ‘evading immune destruction’.This includes the importance of molecular diagnostics according to the new WHO classification and how next generation sequencing is being implemented in the clinical daily life. Molecular results linked together with clinical outcome have revealed the importance of the prognostic biomarker isocitratedehydrogenase (IDH), which is now part of the diagnostic criteria in brain tumours. IDH is discussed in the context of the hallmark ‘reprogramming cellular energetics’. O-6-methylguanine-DNA methyltransferase status predicts a more favourable response to treatment and is thus a predictive marker. Based on genomic aberrations, Verhaak et al have suggested a division of GBM into three subgroups, namely, proneural, classical and mesenchymal, which could be meaningful in the clinic and could help guide and differentiate treatment decisions according to the specific subgroup.The information achieved will develop and improve precision medicine in the future.

show abstract

Section: Methodsmentioning

confidence: 92%

“…In the 2013 TCGA study,11 expression of TERT was found in 21/25 cases accessible for investigation. In the remaining four samples, mutations were found in the transcriptional regulator gene alpha thalassaemia mental retardation ( ATRX ).…”

Section: Methodsmentioning

confidence: 99%

Hallmarks of glioblastoma: a systematic review

2016

View full text Add to dashboard Cite

show abstract

“…The recent assessment of the "genomic landscape" of GB [ 6 ], and the improved knowledge of signaling pathways, have led to great expectations from biologically targeted therapies, specifi cally monoclonal antibodies (mAb) and tyrosine-kinase inhibitors (TKI), as well as active and passive immune therapy [ 7 , 8 ]. However, the numerous clinical trials undertaken on these grounds have generally yielded unsatisfactory results.…”

Section: Prognostic Markers and Treatment Strategiesmentioning

confidence: 99%

Introduction and Background

Pirtoli¹,

Gravina²,

Giordano³

2016

Current Clinical Pathology

View full text Add to dashboard Cite

Glioblastoma (GB) accounts for 54 % of primary brain tumors, with an incidence of about fi ve new cases for every 100,000 per year, and after aggressive multimodal treatments, prognosis remains poor, with a 5-year Overall Survival (OS) rate barely reaching 5 %, as extensively documented in the section of this book dedicated to prognostic parameters of GB. Maximum achievable safe surgical resection, and limited-volume radiotherapy (RT) with concurrent and sequential chemotherapy (CHT) based on the alkylating agent Temozolomide (TMZ) [ 1 ], achieve 40, 15, and 7-8 % OS rates, respectively at 1-, 2-, and 3-years. These present standards of treatment mostly stem from studies dating back to the seventies of the last century [ 2 , 3 ], and progressively evolving through subsequent clinical trials.A great deal of medical literature is dedicated to GB, with increasing frequency over time. Most recent articles on GB, in fact, begin with the statement that prognosis has not improved, despite the numerous research fi ndings on its underlying genomic and molecular mechanisms. This is due at least in part to the diffi culty in improving patient outcomes, given the elusive nature of this disease with respect to therapeutic innovations, including those in the RT domain. Radiation is one of the most used and useful tool against cancer, including GB, and knowledge of its mechanisms of action on biological substrates is of the utmost importance in oncology. Radioresistance of GB is one challenge for Radiation Biology (RB) that has emerged from the clinical setting, and important questions raised by clinical experiences are addressed by basic RB laboratory research. However, RB is a scarcely known discipline outside of the inner circle of the radiological science scholars, and we are convinced that a comprehensive and updated coverage of this subject is warranted, that is, the aim of this book. The researchers and the practitioners studying GB in the domains of radiation and medical oncology, pathology, biology, and physics may profi t from reciprocal scientifi c contributions collected in a lineup fi tting the present state-of-the-art. 2We dedicated the fi rst section of the book to RB topics emerging from clinical studies on GB. These include research regarding RT dose, volume and fractionation, CHT associated with RT, RT modalities alternative to the current photon irradiation, mathematical modeling of treatment parameters, prognostic parameters and markers, and radiation tolerance of normal brain. The second part addresses preclinical research domains of particular relevance for GB. These include related basic experimental RB; immune system and GB microenvironment; genetic and epigenetic determinants in tumor initiation and progression; GB microenvironment in its relationship with hypoxia and glioma stem cellrelated radiation resistance; cell-death pathways and radiation; miRNA manipulation in modifying radiation resistance of GB; and nanoparticle research. The third and last section of the book deals with translational issues,...

show abstract

“…Human glioma progression may sometimes consist of the transition through states that are currently considered as distinct molecular/functional classes, e.g., proneural and mesenchymal subtypes (Brennan et al 2013). Such transitions may be modeled in vivo in PDGF-driven gliomas, as suggested by the altered molecular phenotype and aggressiveness of tumors induced by the concomitant overexpression of PDGF and factors characterizing the mesenchymal subtype such as Stat3 (Doucette et al 2012) or TAZ (Bhat et al 2011).…”

Section: Target Cellsmentioning

confidence: 99%