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| Open AccessComplex MSH2 and MSH6 mutations in hypermutated microsatellite unstable advanced prostate cancer
Several patients with metastatic prostate cancer have been shown to harbour tumours with markedly high mutation rates. Here, the authors characterise hypermutation in advanced prostate cancer samples and show that these samples have somatic mismatch repair gene mutations and microsatellite instability.
- Colin C. Pritchard
- , Colm Morrissey
- & Peter S. Nelson
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Somatic mutations in DROSHA and DICER1 impair microRNA biogenesis through distinct mechanisms in Wilms tumours
Wilms tumour is a common childhood cancer. Here, the authors use whole-exome sequencing in 44 Wilms tumours to characterize their mutational landscape and show that DICER1 and DROSHAmutations can suppress the biogenesis of tumour-suppressing microRNAs.
- Dinesh Rakheja
- , Kenneth S. Chen
- & James F. Amatruda
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Symmetrical and asymmetrical division analysis provides evidence for a hierarchy of prostate epithelial cell lineages
The role of cell division modes of basal and luminal epithelial cells in prostate development and tumorigenesis is unclear. Here, the authors show that while luminal cells contribute to development and tumorigenesis via symmetrical divisions, basal cells do so through asymmetric divisions.
- Jia Wang
- , Helen He Zhu
- & Wei-Qiang Gao
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Article
| Open AccessGermline mutations in the PAF1 complex gene CTR9 predispose to Wilms tumour
Wilms tumour is a childhood kidney cancer that affects 1 in 10,000 children. Here the authors exome sequence 12 individuals with non-syndromic Wilms tumour from six unrelated families and find mutations in CTR9 that may increase risk of developing the disease.
- Sandra Hanks
- , Elizabeth R. Perdeaux
- & Nazneen Rahman
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Increased Notch signalling inhibits anoikis and stimulates proliferation of prostate luminal epithelial cells
Prostate epithelia contain basal, luminal and neuroendocrine cells. Here the authors show that overexpression of the Notch intracellular domain in the mouse prostate promotes proliferation and suppresses anoikis of prostate luminal epithelial cells.
- Oh-Joon Kwon
- , Joseph M. Valdez
- & Li Xin
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Article
| Open AccessRecurrent somatic mutation in DROSHA induces microRNA profile changes in Wilms tumour
Wilms tumour (WT) is the most common paediatric kidney cancer and few driver genes related to its development have been identified. Here, the authors identify DROSHAmutations that may contribute to WT tumorigenesis through their effect on primary microRNA processing.
- Giovana T. Torrezan
- , Elisa N. Ferreira
- & Dirce M. Carraro
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Article
| Open AccessWhole-genome sequencing of bladder cancers reveals somatic CDKN1A mutations and clinicopathological associations with mutation burden
Bladder cancer is a complex genetic disease and a common cause of death due to malignancy. Here, the authors carry out whole-genome sequencing of 14 bladder cancers to characterize the genomic landscape of the disease and show that mutational burden is associated with tumour progression in these samples.
- J. -B. Cazier
- , S. R. Rao
- & F. C. Hamdy
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A common variant at 8q24.21 is associated with renal cell cancer
Renal cell carcinoma (RCC) accounts for 80–90% of all kidney cancers, but to date, only five genome-wide significant RCC risk loci have been identified. Here, Gudmundsson et al.identify a new RCC susceptibility locus and provide insight into the genetic basis of the disease.
- Julius Gudmundsson
- , Patrick Sulem
- & Kari Stefansson
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Peptidomimetic targeting of critical androgen receptor–coregulator interactions in prostate cancer
Androgen receptor signalling plays an important role in driving prostate cancer progression. Here the authors design a peptidomimetic that blocks the interaction between the androgen receptor and its coactivator PELP1, and show that the drug slows prostate cancer cell growth in a xenograft model.
- Preethi Ravindranathan
- , Tae-Kyung Lee
- & Ganesh V. Raj
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Recruitment of mesenchymal stem cells into prostate tumours promotes metastasis
Cancer-associated fibroblasts promote tumour growth and metastasis by secreting signalling molecules. Jung and colleagues show that prostate cancer cells secrete CXC chemokine ligand 16, which recruits mesenchymal stem cells and converts them into cancer-associated fibroblasts.
- Younghun Jung
- , Jin Koo Kim
- & Russell S. Taichman
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Monoallelic expression of TMPRSS2/ERG in prostate cancer stem cells
The TMPRSS2/ERG gene fusion is frequently expressed in prostate cancers, however, its clinical significance is unclear. Polsen et al. show that this gene fusion is expressed monoallelically in prostate cancer stem cells, and may influence their self-renewal and maintenance.
- Euan S. Polson
- , John L. Lewis
- & Norman J. Maitland
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Reliable detection of subclonal single-nucleotide variants in tumour cell populations
The detection of subclonal variants in heterogeneous cancer specimens is a challenge due to errors that occur during sequencing. In this study, a statistical algorithm and a sequencing strategy are reported that circumvent this issue and can accurately detect variants at a frequency as low as 1/10,000.
- Moritz Gerstung
- , Christian Beisel
- & Niko Beerenwinkel
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α-Mannosidase 2C1 attenuates PTEN function in prostate cancer cells
PTEN is a phosphatase that regulates the phosphatidylinositol-3 kinase signalling pathway and is inactivated in many tumour types. Heet al.show that a mannosidase, α-mannosidase 2C1, can inactivate PTEN in prostate cancer cells, and that PTEN-positive human prostate tumours overexpress α-mannosidase 2C1.
- Lizhi He
- , Catherine Fan
- & Damu Tang