Showing papers in "Cancer Cell in 2010"

TL;DR: A robust gene expression-based molecular classification of GBM into Proneural, Neural, Classical, and Mesenchymal subtypes is described and multidimensional genomic data is integrated to establish patterns of somatic mutations and DNA copy number.

TL;DR: Analysis of genomic and clinical outcome data from 218 prostate cancer tumors revealed that copy-number alterations robustly define clusters of low- and high-risk disease beyond that achieved by Gleason score.

TL;DR: Mutational and epigenetic profiling of a large acute myeloid leukemia (AML) patient cohort revealed that IDH1/2-mutant AMLs display global DNA hypermethylation and a specificHypermethylation signature, suggesting a shared proleukemogenic effect.

TL;DR: G-CIMP tumors belong to the proneural subgroup, are more prevalent among lower-grade gliomas, display distinct copy-number alterations, and are tightly associated with IDH1 somatic mutations.

TL;DR: It is reported that tumor 2HG is elevated in a high percentage of patients with cytogenetically normal acute myeloid leukemia (AML), and AML patients with IDH mutations display a significantly reduced number of other well characterized AML-associated mutations and/or associated chromosomal abnormalities, potentially implicating IDH mutation in a distinct mechanism of AML pathogenesis.

TL;DR: It is shown that normal dermal fibroblasts can be "educated" by carcinoma cells to express proinflammatory genes, and this ability to "educate" them is shown to be related to tumor-enhancing inflammation.

TL;DR: Increased IGF-1R and pAKT levels in a post-relapse human tumor sample are consistent with a role for IGF- 1R/PI3K-dependent survival in the development of resistance to BRAF inhibitors.

TL;DR: Using high-throughput FISH analyses in both cell lines and in patients with lung cancer, the potential to prospectively identify treatment naive, patients with EGFR-mutant lung cancer who will benefit from initial combination therapy is highlighted.

TL;DR: These findings provide a working model in which TMPRSS2-ERG plays a critical role in cancer progression by disrupting lineage-specific differentiation of the prostate and potentiating the EZH2-mediated dedifferentiation program.

TL;DR: It is demonstrated that deletion in mice of the 13q14-minimal deleted region (MDR), which encodes the DLEU2/miR-15a/16-1 cluster, causes development of indolent B cell-autonomous, clonal lymphoproliferative disorders, recapitulating the spectrum of CLL-associated phenotypes observed in humans.

TL;DR: DNA methylation profiles segregated patients with CEBPA aberrations from other subtypes of leukemia, defined four epigenetically distinct forms of AML with NPM1 mutations, and showed that established AML1-ETO, CBFb-MYH11, and PML-RARA leukemia entities are associated with specific methylation profile.

TL;DR: These results identify SIRT3 as a genomically expressed, mitochondria-localized tumor suppressor and human breast and other human cancer specimens exhibit reduced Sirt3 levels.

TL;DR: A small molecule inhibitor is described that blocks oncogenic transformation induced by various Rho GTPases in fibroblasts, and the growth of human breast cancer and B lymphoma cells, without affecting normal cells.

TL;DR: It is found that 28% of single melanoma cells obtained directly from patients formed tumors in NOD/SCID IL2Rγ(null) mice, and some melanomas metastasized in mice, irrespective of whether they arose from CD271(-) orCD271(+) cells.

TL;DR: It is shown that overexpression of miR-21 enhances tumorigenesis and that genetic deletion of mi R-21 partially protects against tumor formation, and that overexpression of miRs drives tumorigenisation through inhibition of negative regulators of the Ras/MEK/ERK pathway and inhibition of apoptosis.

TL;DR: It is shown that in ∼80% of primary human CD34+ acute myeloid leukemia (AML), two expanded populations with hemopoietic progenitor immunophenotype coexist in most patients, suggesting that in most cases primaryCD34+ AML is a progenitors disease where LSCs acquire abnormal self-renewal potential.

TL;DR: In this article, the authors investigated functional relationships between SNF5 and EZH2 in oncogenic transformation, and showed that inactivation of Ezh2 blocks tumor formation driven by Snf5 loss.

TL;DR: The results show that the capacities for self-renewal and tumor initiation in GBM need not be restricted to a uniform population of stemlike cells, but can be shared by a lineage of self-Renewing cell types expressing a range of markers of forebrain lineage.

TL;DR: Using the K14-HPV16 mouse model of squamous carcinogenesis, it is reported that B cells and humoral immunity foster cancer development by activating FcGamma receptors (FcgammaRs) on resident and recruited myeloid cells.

TL;DR: A cell population enriched for GICs that expresses high levels of CD44 and Id1 and tend to be located in a perivascular niche is identified, which confer poor prognosis in GBM patients.

TL;DR: It is demonstrated that the mechanisms of tumor regression by anti-HER2/neu antibody therapy also require the adaptive immune response, and the addition of chemotherapeutic drugs, although capable of enhancing the reduction of tumor burden, could abrogate antibody-initiated immunity leading to decreased resistance to rechallenge or earlier relapse.

TL;DR: This work identifies EPI-001, a small molecule that blocked transactivation of the NTD and was specific for inhibition of AR without attenuating transcriptional activities of related steroid receptors.

TL;DR: Mechanistically, itraconazole appears to act on the essential Hh pathway component Smoothened by a mechanism distinct from that of cyclopamine and other known SMO antagonists, and prevents the ciliary accumulation of SMO normally caused by Hh stimulation.

TL;DR: Evidence is provided that miR-192, 194, and 215, which are downregulated in a subset of newly diagnosed MMs, can be transcriptionally activated by p53 and then modulate MDM2 expression, and that their downregulation plays a key role in MM development.

TL;DR: The 4EBP-eIF4E axis downstream of mTOR is a druggable mediator of translational control and Akt-mediated tumorigenesis that has important implications for the treatment of human cancers.

TL;DR: A transplant system that allows initiated mouse hepatocytes to form hepatocellular carcinomas (HCC) in host liver after a long latency and deletion of IKKbeta long after initiation accelerated HCC development and enhanced proliferation of tumor initiating cells.

TL;DR: It is demonstrated that repetitive exposure to tobacco smoke promotes tumor development both in carcinogen-treated mice and in transgenic mice undergoing sporadic K-ras activation in lung epithelial cells.

TL;DR: Targeting Cdk4 alleles in advanced tumors detectable by computed tomography scanning also induces senescence and prevents tumor progression, suggesting that robust and selective pharmacological inhibition of Cdk 4 may provide therapeutic benefit for NSCLC patients carrying K-RAS oncogene.

TL;DR: It is shown that increased Zeste homolog 2 (EZH2) expression in either tumor cells or in tumor vasculature is predictive of poor clinical outcome, and the potential for targeting ezh2 as an important therapeutic approach is supported.

TL;DR: 4E-BP1 plays a prominent role in mediating the effects of these pathways in tumors in which they are activated by mutation, and provides mechanistic bases for the limited activity of AKT and MEK inhibitors in tumors with comutation of both pathways.