Scientific Publications Archive
The Genetic Landscape of the Childhood Cancer Medulloblastoma
December 16, 2010
Through whole exome sequencing, researchers have found that pediatric medulloblastoma, the most common malignant brain tumor found in children, contains a fraction of the mutations found in adult cancers. These findings, reported in the December 16 issue of Science, reveal that mutations of genes involved in normal developmental processes occur with greater frequency in medulloblastoma tumors.
Towards Patient-Based Cancer Therapeutics
Genomic analysis of primary tumors is providing extraordinary insights into the molecular changes in genes and pathways that cause cancer. Researchers from the NCI Cancer Target Discovery and Development (CTD²) network are relating the genetic features of cancers to acquired gene and pathway dependencies and identifying small-molecule therapeutics that target them.
TARGET researchers have discovered eight unique subgroups among patients with pediatric high-risk B-precursor acute lymphoblastic leukemia (ALL). These subgroups can be distinguished by high-level expression of unique “outlier” genes, distinct DNA copy number abnormalities, specific clinical features and significantly different rates of relapse-free survival. The research demonstrates the striking biologic, genetic and clinical complexity within high-risk ALL, and uncovers novel genes which may serve as new targets for diagnosis, risk classification and therapy.
Outcomes for Children and Adolescents With Cancer: Challenges for the Twenty-First Century
Journal of Clinical Oncology
May 20, 2010
Leaders from the NCI Cancer Therapy Evaluation Program (CTEP) and the Children’s Oncology Group provide an overview of the most current childhood cancer statistics, an analysis of the impact past research discoveries have had on survival and treatment outcomes, and essential information for prioritizing future treatment and research directions.
The Genome of the Western Clawed Frog Xenopus tropicalis
April 30, 2010 Epub
Researchers have sequenced the genome of the western clawed frog (Xenopus tropicalis). The frog is a vertebrate developmental model that may provide insights into cell division and differentiation, two concepts important to understanding cancer.
TCGA researchers identified four distinct molecular subtypes of glioblastoma multiforme (GBM), and demonstrated that response to aggressive chemotherapy and radiation differed by subtype. These findings, reported in the January 19 issue of Cancer Cell, may result in more personalized approaches to treating groups of GBM patients based on their genetic alterations.
Somatic mutation of EZH2 (Y641) in Follicular and Diffuse Large B-cell Lymphomas of Germinal Center Origin
January 17, 2010 as an Epub ahead of print
Morin et al. describe recurrent somatic mutations in EZH2, a polycomb group oncogene. The mutation, found in the SET domain of this gene encoding a histone methyltransferase, is found only in a subset of lymphoma samples. Specifically, EZH2 mutations are found in about 12% of follicular lymphomas (FL) and almost 23% of diffuse large B-cell lymphomas (DLBCL) of germinal center origin. This paper goes on to demonstrate that altered EZH2 proteins, corresponding to the most frequent mutations found in human lymphomas, have reduced activity using in vitro histone methylation assays. Together, these results highlight a conserved biologic pathway important for DLBCL and FL pathogenesis.
Gene Expression Classifiers for Relapse-Free Survival and Minimal Residual Disease Improve Risk Classification and Outcome Prediction in Pediatric B-Precursor Acute Lymphoblastic Leukemia
October 30, 2009 as an Epub ahead of print
TARGET researchers used gene expression profiling to improve their ability to predict the outcome of children with acute lymphoblastic leukemia (ALL). Their research generated a 38-gene expression classifier predictive of relapse-free survival (RFS). Together with flow cytometry data, they were able to classify specific groups of high-risk patients into low, intermediate or high risk subgroups. This data demonstrates that gene expression profiles can improve ALL classification and help to prospectively identify children that respond or fail current treatment regimens. These trials were registered at http://clinicaltrials.gov under NCT00005603. [Read Abstract]
Identification of a New Prostate Cancer Susceptibility Locus on Chromosome 8q24
September 20, 2009 as an Advance Online Publication
CGEMS researchers announce discovery of new area on chromosome 8 that is associated with risk for prostate cancer. This publication describes a specific variant at 8q24 that is associated with prostate cancer. This study, along with additional papers published in parallel, all found this region to be associated with prostate cancer risk.
The Completion of the Mammalian Gene Collection (MGC)
September 18, 2009 as an Advance Online Publication
The MGC Project Team announces the completion of the Mammalian Gene Collection. This publication describes the process of creating and validating more than 100,000 full-length open reading frames from human, mouse, rat, cow, frog and zebrafish. Each of these is now available to the research community through the MGC website.
JAK Mutations in High-Risk Childhood Acute Lymphoblastic Leukemia
Proceedings of the National Academy of Sciences
June 9, 2009
Vol. 106 / No. 23
TARGET researchers built on their discoveries in acute lymphoblastic leukemia (ALL). They identified mutations in a class of protein kinase genes called the janus kinases (JAK) in high-risk ALL patients. Mutations in the JAK gene frequently occurred alongside alterations of IKAROS, (see below, NEJM). Importantly, almost 80% of patients with mutations in a JAK gene and deletion or mutations in IKAROS relapsed within four years compared to only 23% of patients with neither mutation.
A Multistage Genome-Wide Association Study in Breast Cancer Identifies Two New Risk Alleles at 1p11.2 and 14q24.1 (RAD51L1)
Vol. 41 / No. 5 (March 29, 2009 Epub)
CGEMS Researchers have identified new genetic variations in two regions of DNA — located on chromosomes 1 and 14 — that may be associated with the risk of sporadic breast cancer. This study also confirms some of the previously identified associations between specific regions in the genome and breast cancer risk.
Genome Studies Yield Insights into Childhood Leukemia
NCI Cancer Bulletin
January 13, 2009
Volume 6 / Number 1
This "Special Report" in the NCI Cancer Bulletin features the first results from the TARGET Initiative, highlighting the discovery of the genetic changes associated with children treated for acute lymphoblastic leukemia (ALL) and their risk for relapse. TARGET collaborators analyzed two independent groups of ALL patients with high rates of relapse to reveal that the gene mutation of IKAROS (or IKZF1) increased the risk for recurrence, which may help to explain why chemotherapy fails for some patients. These findings could lead to genetic tests that identify ALL patients at high risk for relapse and those who may benefit from more aggressive treatments.
Deletion of IKZF1 and Prognosis in Acute Lymphoblastic Leukemia
The New England Journal of Medicine
January 7, 2009
NCI's TARGET Initiative reported the discovery of a novel genetic marker for children with acute lymphoblastic leukemia (ALL) in the January 7, 2009, advance online edition of The New England Journal of Medicine. The genetic alteration identified, IKZF1, should improve clinicians' ability to identify high-risk patients and better assign these patients to appropriate therapy.
Comprehensive Genomic Characterization Defines Human Glioblastoma Genes and Core Pathways
October 23, 2008
The Cancer Genome Atlas Research Network reported the first results of its large-scale, comprehensive study of the most common form of brain cancer, glioblastoma (GBM) in the advance online edition of the journal Nature, released September 4, 2008. Among the TCGA findings are the identification of many gene mutations involved in GBM, including three previously unrecognized mutations that occur with significant frequency; and the delineation of core pathways disrupted in this type of brain cancer. One of the most exciting results is an unexpected observation that points to a potential mechanism of resistance to a common chemotherapy drug used for brain cancer.
*Advance online edition released September 4, 2008; final article published in the October 23, 2008 issue of Nature.
Genome Surveys Reveal Complexity of Brain Cancers
NCI Cancer Bulletin
September 9, 2008
Volume 5 / Number 18
This NCI Cancer Bulletin article features one of the most comprehensive studies to date of the molecular changes underlying brain cancer. The TCGA Research Network analyzed 206 glioblastoma (GBM) brain tumors using an integrated approach based on multiple types of genetic data and clinical information. Highlighting three genes found in the disease – ERBB2, NF1, and TP53, these findings significantly expand our current knowledge about the genetic networks involved in this deadly disease and potential therapeutic strategies.
TCGA Moving Molecular Oncology Forward
NCI Cancer Bulletin
May 27, 2008
Volume 5 / Number 11
This guest update by Dr. Daniela S. Gerhard looks at the progress of TCGA pilot project and the value seen by researchers through data being developed and shared across the globe along with its offering of new technologies and tools to propel molecular oncology with precision and efficiency.
Multiple Loci Identified in a Genome-Wide Association Study of Prostate Cancer
February 10, 2008
Vol 40, Issue 3
The prostate cancer study looks at the association between multiple loci and the susceptibility to prostate cancer, which could be used as an indicator for high risk individuals (subscription required).
Common Genetic Variants Linked to Breast Cancer
NCI Cancer Bulletin
May 29, 2007
Volume 4 / Number 18
Researchers have identified common genetic variations associated with breast cancer in several populations of women. The variants occur in a tumor suppressor gene called FGFR2 (Fibroblast Growth Factor Receptor 2), which was previously reported to be amplified or overexpressed in some breast cancers.
Small Molecules, Big Players: the National Cancer Institute's Initiative
for Chemical Genetics
AACR Cancer Research
September 15, 2006
The Initiative for Chemical Genetics (ICG), created by NCI, enables public research using small molecules to accelerate the discovery of cancer-relevant small-molecule probes. This report outlines how the ICG functions, how researchers can take advantage of its screening, chemistry and informatic capabilities, and provides a brief summary of some of the many important research findings (subscription required).
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