Featured
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Letter |
The deubiquitinase USP9X suppresses pancreatic ductal adenocarcinoma
An in vivo transposon screen in a pancreatic cancer model identifies frequent inactivation of Usp9x; deletion of Usp9x cooperates with KrasG12D to accelerate rapidly pancreatic tumorigenesis in mice, validating their genetic interaction.
- Pedro A. Pérez-Mancera
- , Alistair G. Rust
- & David A. Tuveson
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Article |
The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups
Integrative analysis of copy number and gene expression in 2,000 primary breast tumours with long-term clinical follow-up revealed putative cis-acting driver genes, novel subgroups and trans-acting aberration hotspots that modulate subgroup-specific gene networks.
- Christina Curtis
- , Sohrab P. Shah
- & Samuel Aparicio
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Letter |
The clonal and mutational evolution spectrum of primary triple-negative breast cancers
Primary triple-negative breast cancers are shown to vary widely and continuously in the degree of clonal evolution and mutational content at the time of diagnosis, with implications for future studies of the disease.
- Sohrab P. Shah
- , Andrew Roth
- & Samuel Aparicio
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Letter |
The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity
The Cancer Cell Line Encyclopedia presents the first results from a large-scale screen of some 947 cancer cell lines with 24 anticancer drugs, with the aim of identifying specific genomic alterations and gene expression profiles associated with selective sensitivity or resistance to potential therapeutic agents.
- Jordi Barretina
- , Giordano Caponigro
- & Levi A. Garraway
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Letter |
A murine lung cancer co-clinical trial identifies genetic modifiers of therapeutic response
In parallel with an ongoing human clinical trial, genetically engineered mouse models of lung cancer with different genetic alterations are treated with chemotherapeutic agents; the results have implications for the clinical trial.
- Zhao Chen
- , Katherine Cheng
- & Kwok-Kin Wong
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News & Views |
Sorting out the sirtuins
Debates over the role of sirtuin proteins in ageing are maturing into functional assessments of the individual proteins. It seems that overexpression of a specific sirtuin can extend lifespan in male mice. See Letter p.218
- David B. Lombard
- & Richard A. Miller
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Letter
| Open AccessSequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes
Whole-genome sequencing of neuroblastoma, a childhood tumour of the nervous system, shows that chromothripsis (a local shredding of chromosomes) and mutations in genes regulating neurite growth are associated with the most aggressive tumours.
- Jan J. Molenaar
- , Jan Koster
- & Rogier Versteeg
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Article |
The translational landscape of mTOR signalling steers cancer initiation and metastasis
Ribosome profiling reveals specialized translation of the prostate cancer genome by oncogenic mTOR signalling; stringent inhibition of mTOR signalling reduces prostate cancer invasion and metastasis in a mouse model.
- Andrew C. Hsieh
- , Yi Liu
- & Davide Ruggero
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News |
Field narrows in hunt for devil tumour genes
Genome sequences of the Tasmanian devil's infectious cancer stir hopes for a vaccine.
- Ewen Callaway
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News & Views |
Evolution after tumour spread
A genetic study of brain cancers in mice and humans reveals distinct mutations in primary tumours and their metastases, suggesting that the two disease 'compartments' may require different treatments.
- Steven C. Clifford
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Letter |
IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype
Mutation of isocitrate dehydrogenase 1 (IDH1) is shown to induce DNA hypermethylation and to remodel the epigenome to resemble that of gliomas with the CpG island methylator phenotype.
- Sevin Turcan
- , Daniel Rohle
- & Timothy A. Chan
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News |
Norway to bring cancer-gene tests to the clinic
A pilot programme will use latest tumour-sequencing techniques to help guide cancer care.
- Ewen Callaway
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Research Highlights |
Genome shatters in brain cancer
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Article
| Open AccessA novel retinoblastoma therapy from genomic and epigenetic analyses
The retinoblastoma genome is shown to be stable, but multiple cancer pathways are identified that are epigenetically deregulated, providing potential new therapeutic targets.
- Jinghui Zhang
- , Claudia A. Benavente
- & Michael A. Dyer
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Article
| Open AccessThe genetic basis of early T-cell precursor acute lymphoblastic leukaemia
This work shows that treatments used for acute myeloid leukaemia and targeted therapies could be used for early T-cell precursor acute lymphoblastic leukaemia.
- Jinghui Zhang
- , Li Ding
- & Charles G. Mullighan
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Letter |
Functional genomics reveal that the serine synthesis pathway is essential in breast cancer
- Richard Possemato
- , Kevin M. Marks
- & David M. Sabatini
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Research Highlights |
Breast-cancer weaknesses found
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News & Views |
Genomic evolution of metastasis
Prognosis for patients with pancreatic cancer is bleak, often owing to late diagnosis. The estimate that at least 15 years pass from tumour initiation to malignancy offers hope for early detection and prevention. See Letters p.1109 & p.1114
- E. Georg Luebeck
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Letter |
The patterns and dynamics of genomic instability in metastatic pancreatic cancer
Pancreatic cancer is highly aggressive, usually because of widespread metastasis. Here, next-generation DNA sequencing has been used to detect genomic rearrangements in 13 patients with pancreatic cancer and to explore clonal relationships among metastases. The results reveal not only considerable inter-patient heterogeneity, but also ongoing genomic instability and evolution during the development of metastases.
- Peter J. Campbell
- , Shinichi Yachida
- & P. Andrew Futreal
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Letter |
ETV1 is a lineage survival factor that cooperates with KIT in gastrointestinal stromal tumours
Gastrointestinal stromal tumours (GIST) are believed to arise in interstitial cells of Cajal (ICC). These authors show that the transcription factor ETV1 is required for ICC development and promotes the development of GIST. KIT, which is often activated by mutations in GIST, cooperates with ETV1 in the transformation of ICCs, in part by promoting ETV1 stabilization. Thus, a normal developmental lineage factor is switched into a tumour-promoting factor by a cooperating oncogene.
- Ping Chi
- , Yu Chen
- & Charles L. Sawyers
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Research Highlights |
Cancer biology: Ovarian cancer culprits
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Research Highlights |
Cancer genomics: Probing prostate cancer
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Research Highlights |
Cancer genomics: Prognostic sign
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Letter |
The mutation spectrum revealed by paired genome sequences from a lung cancer patient
Complete genome sequencing has already provided insights into the mutation spectra of several cancer types. Here, the first complete sequences are provided of a primary lung tumour and adjacent normal tissue. Comparison of the two reveals a variety of somatic mutations in the cancer genome, including changes in the KRAS proto-oncogene. The results reveal a distinct pattern of selection against mutations within expressed genes compared to non-expressed genes, and selection against mutations in promoter regions.
- William Lee
- , Zhaoshi Jiang
- & Zemin Zhang
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Perspective |
International network of cancer genome projects
- Thomas J. Hudson (Chairperson)
- , Warwick Anderson
- & Huanming Yang
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Article |
Genome remodelling in a basal-like breast cancer metastasis and xenograft
Massively parallel DNA sequencing allows entire genomes to be screened for genetic changes associated with tumour progression. Here, the genomes of four DNA samples from a 44-year-old African-American patient with basal-like breast cancer were analysed. The samples came from peripheral blood, the primary tumour, a brain metastasis and a xenograft derived from the primary tumour. The findings indicate that cells with a distinct subset of the primary tumour mutation might be selected during metastasis and xenografting.
- Li Ding
- , Matthew J. Ellis
- & Elaine R. Mardis
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News & Views |
Genomics of metastasis
Cancer cells that invade other parts of the body do so by accumulating genomic aberrations. Analysis of the genomic differences between primary and metastatic tumours should aid the understanding of this process.
- Joe Gray
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News Feature |
Big science: The cancer genome challenge
Databases could soon be flooded with genome sequences from 25,000 tumours. Heidi Ledford looks at the obstacles researchers face as they search for meaning in the data.
- Heidi Ledford
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Opinion |
Counterpoint: Data first
Large, unbiased genomic surveys are taking cancer therapeutics in directions that could never have been predicted by traditional molecular biology, says Todd Golub. This Opinion piece is part of a linked pair; see also Point: Hypothesis First by Robert Weinberg.
- Todd Golub
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Research Highlights |
Cancer genomics: Melanoma's mutations
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Article
| Open AccessSignatures of mutation and selection in the cancer genome
Homozygous gene deletions in cancer cells occur over recessive cancer genes (where they can confer selective growth advantage) or over genes at fragile sites of the genome (where they are thought to reflect increased DNA breakage). Here, a large number of homozygous deletions in a collection of cancer cell lines are identified and analysed to derive structural signatures for the two different types of deletion. More deletions are found in inherently fragile regions, and fewer overlying recessive genes.
- Graham R. Bignell
- , Chris D. Greenman
- & Michael R. Stratton
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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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News |
Genomics boosts brain-cancer work
Molecular findings start to open up avenues of diagnosis and treatment.
- Erika Check Hayden
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