Featured
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News |
Personalized biomarkers monitor cancer
Pilot study harnesses sequencing power to track tumours.
- Heidi Ledford
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Article |
The landscape of somatic copy-number alteration across human cancers
One way of discovering genes with key roles in cancer development is to identify genomic regions that are frequently altered in human cancers. Here, high-resolution analyses of somatic copy-number alterations (SCNAs) in numerous cancer specimens provide an overview of regions of focal SCNA that are altered at significant frequency across several cancer types. An oncogenic function is also found for the anti-apoptosis genes MCL1 and BCL2L1, which reside in amplified genome regions in many cancers.
- Rameen Beroukhim
- , Craig H. Mermel
- & Matthew Meyerson
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News |
How accurate are cancer cell lines?
Some argue that tumour cells obtained directly from patients are the best way to study cancer genomics.
- Brendan Borrell
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Brief Communications Arising |
Chronic DLL4 blockade induces vascular neoplasms
- Minhong Yan
- , Christopher A. Callahan
- & Greg D. Plowman
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Research Highlights |
Stem cells: Uneven divide
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Letter |
TGF-β–FOXO signalling maintains leukaemia-initiating cells in chronic myeloid leukaemia
Chronic myeloid leukaemia is caused by a BCR-ABL fusion, a constitutively active tyrosine kinase that, it is believed, leads to suppression of the forkhead O transcription factors (FOXO). Although the use of the tyrosine kinase inhibitor imatinib is a breakthrough for CML therapy, imatinib does not deplete the leukaemia-initiating cells (LICs) that drive the recurrence of CML. Foxo3a is now shown to have an essential role in the maintenance of CML LICs in a mouse model.
- Kazuhito Naka
- , Takayuki Hoshii
- & Atsushi Hirao
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Books & Arts |
The woman behind HeLa
Steve Silberman enjoys a moving account that probes racial and ethical issues in medicine through the story of the young mother whose death from cancer led to the first immortal cell line.
- Steve Silberman
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News & Views |
Big roles for small RNAs
Embryonic stem cells can create copies of themselves, but can also mature into almost any type of cell in the body. Tiny gene regulators called microRNAs are now shown to have a role in directing these properties.
- Frank J. Slack
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Letter |
RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth
The RAS–RAF signalling pathway is an attractive target for drug development in oncology, and several RAF inhibitors are being tested in clinical trials. Here and in an accompanying paper, RAF inhibitors are shown to have opposing roles, functioning as either inhibitors or activators of RAF depending on the cellular context and mutational status of RAF. The mechanistic basis for these opposing roles is dissected. The results have implications for the clinical use of these inhibitors and for the design of kinase inhibitors.
- Georgia Hatzivassiliou
- , Kyung Song
- & Shiva Malek
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News |
Project set to map marks on genome
Consortium sets sights on the differences that make us different.
- Alison Abbott
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Research Highlights |
Cancer biology: Weighted cancer risk
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News Feature |
Translational research: Talking up translation
Alan Ashworth took a cancer drug from Petri dish to patients in near record speed. Daniel Cressey meets a biologist who is evangelical about translational research.
- Daniel Cressey
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Letter |
Hsp70 stabilizes lysosomes and reverts Niemann–Pick disease-associated lysosomal pathology
Heat shock protein 70 (Hsp70) is a molecular chaperone which, by inhibiting lysosomal membrane permeabilization, promotes the survival of stressed cells. Hsp70 is now shown to stabilize lysosomes by binding to an anionic phospholipid, BMP, resulting in stimulation of acid sphingomyelinase (ASM) activity. Notably, the decreased ASM activity and lysosomal stability seen in patients with Niemann–Pick disease can be corrected by treatment with recombinant Hsp70.
- Thomas Kirkegaard
- , Anke G. Roth
- & Marja Jäättelä
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News |
Lawsuit rekindles gene-patent debate
Criticism of exclusive licences puts university policies in the spotlight.
- Brendan Borrell
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News |
Genomics boosts brain-cancer work
Molecular findings start to open up avenues of diagnosis and treatment.
- Erika Check Hayden
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Research Highlights |
Cancer biology: Kicking out cancer cells
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Letter |
Interaction between RasV12 and scribbled clones induces tumour growth and invasion
In human tumours, complex cell interactions in the tumour and its microenvironment are thought to have an important role in tumorigenesis and cancer progression. In a genetically well-defined model system in Drosophila, clones of cells bearing different mutations are now shown to cooperate to promote tumour growth and invasion. This interaction involves JNK signalling propagation and JNK-induced upregulation of JAK/STAT-activating cytokines.
- Ming Wu
- , José Carlos Pastor-Pareja
- & Tian Xu
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Letter |
Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma
The role of B-cell-receptor (BCR) signalling in human B cell lymphomas has been a long-standing question, with genetic and functional evidence for its oncogenic role in human lymphomas lacking. Here, a form of 'chronic active' BCR signalling that is required for cell survival in the activated B-cell-like subtype of diffuse large B-cell lymphoma is described and analysed, with potential implications for future therapeutic strategies.
- R. Eric Davis
- , Vu N. Ngo
- & Louis M. Staudt
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Letter |
Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes
Clear cell renal carcinoma, the most common form of adult kidney cancer, is often characterized by the presence of inactivating mutations in the VHL gene. A large survey for somatic mutations now identifies inactivating mutations in two genes encoding enzymes involved in histone modification, highlighting the role of mutations in components of the chromatin modification machinery in human cancer.
- Gillian L. Dalgliesh
- , Kyle Furge
- & P. Andrew Futreal
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