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Comprehensive genomic characterization defines human glioblastoma genes and core pathways.

Author: Cancer Genome Atlas Research Network
Publication venue: eScholarship, University of California
Publication date: 01/10/2008
Field of study

Human cancer cells typically harbour multiple chromosomal aberrations, nucleotide substitutions and epigenetic modifications that drive malignant transformation. The Cancer Genome Atlas (TCGA) pilot project aims to assess the value of large-scale multi-dimensional analysis of these molecular characteristics in human cancer and to provide the data rapidly to the research community. Here we report the interim integrative analysis of DNA copy number, gene expression and DNA methylation aberrations in 206 glioblastomas--the most common type of adult brain cancer--and nucleotide sequence aberrations in 91 of the 206 glioblastomas. This analysis provides new insights into the roles of ERBB2, NF1 and TP53, uncovers frequent mutations of the phosphatidylinositol-3-OH kinase regulatory subunit gene PIK3R1, and provides a network view of the pathways altered in the development of glioblastoma. Furthermore, integration of mutation, DNA methylation and clinical treatment data reveals a link between MGMT promoter methylation and a hypermutator phenotype consequent to mismatch repair deficiency in treated glioblastomas, an observation with potential clinical implications. Together, these findings establish the feasibility and power of TCGA, demonstrating that it can rapidly expand knowledge of the molecular basis of cancer

eScholarship - University of California

Evaluation of the impact of National Breast Cancer Foundation-funded research

Author: Cancer Research Leadership Forum
Hanney S
National Breast Cancer Foundation
National Breast Cancer Foundation
Panel on Return on Investment in Health Research
UK Evaluation Forum
Wooding S
Publication venue: 'AMPCo'
Publication date: 01/03/2014
Field of study

© Copyright 2014. The Medical Journal of Australia - reproduced with permission.Objective: To evaluate the impact of the National Breast Cancer Foundation’s (NBCF’s) research investment. Design and participants: Surveys based on the Payback Framework were sent to chief investigators involved in research funded by the NBCF during 1995–2012; a bibliometric analysis of NBCF-funded publications in 2006–2010 was conducted; and a purposive, stratified sample of case studies was obtained. Main outcome measures: Research impact on knowledge production, the research system, informing policy, product development and broader health and economic benefits. Results: Of 242 surveys sent, 153 (63%) were returned. The average impact of journals in which NBCF publications appeared was double that of world publications. Seventy surveys (46%) reported career progression, and 185 higher degrees were obtained or expected, including 121 PhDs. One hundred and one grants (66%) produced tools that built capacity across the research system, and research teams leveraged an additional $1.40 in funding for every dollar invested. Fifteen applied grants and one basic grant impacted on policy. Ten basic and four applied grants led to the development of drugs, prognostic tools or diagnostic technologies. Twenty applied and two basic grants led to changes in practice and behaviour of health care staff, consumers and the public, with further impacts anticipated. Case studies provided illustrations of high impact. Conclusions: NBCF’s strategy of investing in a mixed portfolio of research areas and mechanisms encouraged a broad range of impacts across all Payback categories. The impacts from basic research tended to focus on knowledge production and drug development; while applied research generated greater impacts within the other Payback categories. The funding of shared infrastructure stimulated impact across the research system

Crossref

Greenwich Academic Literature Archive

The Australian National University

Brunel University Research Archive