Cancer

  • Article |

    Cutaneous melanoma is an aggressive form of skin cancer. Here, the authors show that mutations in the TERT promoter of 287 primary melanomas are associated with age, Breslow thickness and tumour ulceration and frequently occur at sun-exposed sites.

    • Barbara Heidenreich
    • , Eduardo Nagore
    •  & Rajiv Kumar
  • Article |

    Defects in the homologous recombination repair of DNA can result in gene mutation and cancer. In this study, Peng et al.identify a gene signature associated with homologous recombination repair deficiency and show that this can be used both to predict repair defects and clinical outcome in cancer patients.

    • Guang Peng
    • , Curtis Chun-Jen Lin
    •  & Shiaw-Yih Lin
  • Article
    | Open Access

    Renin cells have traditionally been associated with the kidney where they regulate blood pressure and fluid electrolyte homeostasis. In this study, Belyea et al.describe a renin progenitor in the bone marrow that gives rise to B-cell leukaemia when RBP-J, the final effector of the Notch pathway, is deleted.

    • Brian C. Belyea
    • , Fang Xu
    •  & R. Ariel Gomez
  • Article |

    Many studies provide evidence of genes that are associated with cancer prognosis but a global view of these genes is lacking. Using data from ‘The Cancer Genome Atlas’, Yang et al.investigate the network properties of prognostic genes and show that these genes tend to be within highly interconnected groups but not the most connected nodes in the gene co-expression network.

    • Yang Yang
    • , Leng Han
    •  & Han Liang
  • Article |

    R-spondin 2 has an important role in development but its function in cancer has not been described. In this study, Wu et al. demonstrate that R-spondin 2 is decreased in expression in colorectal cancer and this is associated with promoter methylation and inhibition of Wnt signalling.

    • Changjie Wu
    • , Sunquan Qiu
    •  & Xincheng Lu
  • Article |

    Cellular metabolism is dysregulated in cancer and may be reflected in differences in the expression of metabolic genes. In this study, the authors find that mitochondrial folate-coupled dehydrogenase is increased in expression in a wide variety of cancers and negatively correlates with breast cancer patient survival.

    • Roland Nilsson
    • , Mohit Jain
    •  & Vamsi K. Mootha
  • Article |

    Lgr5 is a protein that is important for the maintenance of intestinal homeostasis. In this study, the authors demonstrate that Lgr5 is required for colorectal cancer development and its expression is regulated by the transcription factor GATA6.

    • Shinnosuke Tsuji
    • , Yoshihiro Kawasaki
    •  & Tetsu Akiyama
  • Article |

    Ovarian cancer is one of the most common cancers in women and has an average 5-year survival of only 43%. Here, Kanchi et al.describe the germline and somatic mutation spectrum in ovarian cancer patients and identify potential risk variants associated with the disease.

    • Krishna L. Kanchi
    • , Kimberly J. Johnson
    •  & Li Ding
  • Article |

    Spitzoid neoplasms constitute a spectrum of melanocytic tumours, characterized by distinct clinical, pathological and genetic features. Here, Wiesner et al. show that kinase fusions represent the majority of oncogenic aberrations in spitzoid neoplasms and may serve as therapeutic targets for metastatic spitzoid melanoma.

    • Thomas Wiesner
    • , Jie He
    •  & Boris C. Bastian
  • Article
    | Open Access

    A role for the serpin maspin has been described in both development and cancer. In this study, the authors demonstrate that maspin knockout mice develop normally and that maspin does not function as a tumour suppressor, suggesting that another gene at the maspin locus may be responsible for this activity.

    • Sonia S. Y. Teoh
    • , Jessica Vieusseux
    •  & Phillip I. Bird
  • Article |

    Autophagy prolongs the survival of cells in stressful conditions but its role in cancer is unclear. Here, Rao et al. show that loss of the autophagic protein Atg5 enhanced cancer incidence but impaired tumour progression in a mouse model of lung cancer.

    • Shuan Rao
    • , Luigi Tortola
    •  & Josef M. Penninger
  • Article
    | Open Access

    Multiple myeloma is a malignant plasma cell disorder with a complex molecular pathogenesis. Here, the authors perform whole-exome sequencing, copy-number profiling and cytogenetic analysis in 84 myeloma samples and highlight the diversity and evolution of the mutational profile underlying the disease.

    • Niccolo Bolli
    • , Hervé Avet-Loiseau
    •  & Nikhil C. Munshi
  • Article
    | Open Access

    Non-coding RNAs have recently emerged as crucial regulators of gene expression. Here Rutnam et al.identify a pseudogene complementary to the 3′-UTR of the TUSC2 tumour suppressor that regulates TUSC2 levels by acting as a decoy for endogenous microRNAs and thereby inhibits tumorigenesis.

    • Zina Jeyapalan Rutnam
    • , William W. Du
    •  & Burton B. Yang
  • Article
    | Open Access

    Ovarian cancer is often diagnosed at a late stage when metastasis has already occurred. In this study, Parikh et al.show that mir-181a is involved in mediating the epithelial-to-mesenchymal transition in ovarian cancer, leading to activation of the TGF-β signalling pathway and metastasis.

    • Aditya Parikh
    • , Christine Lee
    •  & Analisa DiFeo
  • Article |

    The majority of ovarian granulosa tumours harbour the C134W mutation in FOXL2 but the mechanism of tumorigenesis is largely unknown. Here, Kim et al. show that mutant FOXL2 is hyperphosphorylated by GSK3β, which targets the protein for degradation, and find that GSK3β inhibition represses the growth of ovarian granulosa cells.

    • Jae-Hong Kim
    • , Yong-Hak Kim
    •  & Jeehyeon Bae
  • Article |

    Glioblastoma cancers contain brain tumour-initiating cells and targeting these specific cells is an attractive opportunity for therapy. In this study, the authors show that FOXG1 and Groucho/TLE transcription factors are important for glioblastoma growth and might be useful therapeutic targets.

    • Federica Verginelli
    • , Alessandro Perin
    •  & Stefano Stifani
  • Article
    | Open Access

    The Hippo tumour suppressor pathway is inactivated in many cancer types, but how this occurs is unclear. Here, the authors show that integrin-linked kinase (ILK) has a role in inhibiting the Hippo pathway and pharmacological inhibition of ILK reduces the size of tumours in mice.

    • Isabel Serrano
    • , Paul C. McDonald
    •  & Shoukat Dedhar
  • Article |

    Many cancers harbour mutations in the tumour suppressor p53, which often then gains oncogenic functions. Here, the authors show that mutant p53 enhances glycolysis in tumour cells by promoting glucose uptake via a mechanism involving GLUT1, RhoA and ROCK.

    • Cen Zhang
    • , Juan Liu
    •  & Zhaohui Feng
  • Article |

    Insulinomas develop from pancreatic β-cells and secrete insulin, but the underlying genetic defects are largely unknown. In this study, Cao et al. identify recurrent T372R mutations in the transcription factor YY1, and validate this hotspot mutation in 30% of insulinomas.

    • Yanan Cao
    • , Zhibo Gao
    •  & Guang Ning
  • Article |

    Whether microRNA processing mediated by Dicer is regulated in a cell-cycle-dependent manner is unknown. Here, Chen et al.show that Cyclin D1, which is important in the control of the cell cycle, regulates the expression of Dicer, and that Cyclin D1 and Dicer expression levels correlate in breast cancer.

    • Zuoren Yu
    • , Liping Wang
    •  & Richard G. Pestell
  • Article |

    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
  • Article |

    Nodal signalling has been implicated in the asymmetric positioning of various organs. Here, Noël et al.show that the asymmetry of the embryonic zebrafish heart is also established in the absence of Nodal signalling, suggesting a Nodal-independent mechanism that relies on actomyosin activity.

    • Emily S. Noël
    • , Manon Verhoeven
    •  & Jeroen Bakkers
  • Article |

    The miR-372-3 cluster has a role in oncogenesis. In this study, by utilizing parthenogenetic induced pluripotent stem cells, that lack the paternal genome, Stelzer et al.report that these miR-372-3 are negatively regulated by a paternally imprinted antisense transcript and that loss of its expression promotes oncogenesis.

    • Yonatan Stelzer
    • , Ido Sagi
    •  & Nissim Benvenisty
  • Article
    | Open Access

    Activating mutations in the Wnt signalling pathway are associated with colon cancer. Here the authors show that tumour cells carrying mutations in APC and β-catenin are still regulated by Wnt ligands, suggesting that Wnt secretion and receptor signalling remains important to control downstream signalling.

    • Oksana Voloshanenko
    • , Gerrit Erdmann
    •  & Michael Boutros
  • Article |

    Semiconductor-based, non-optical DNA sequencing technologies such as Ion Torrent sequencing offer speed and cost advantages compared with alternative techniques. Cheng et al. demonstrate a protocol allowing the use of Ion Torrent technology to sequence DNA from chromatin immunoprecipitation experiments.

    • Christine S. Cheng
    • , Kunal Rai
    •  & Ido Amit
  • Article
    | Open Access

    PALB2 is a BRCA1-/BRCA2-interacting protein and heterozygous mutations in PALB2 are associated with hereditary breast cancer predisposition. Here the authors show that human lymphoblastoid cells from heterozygous PALB2mutation carriers display abnormal DNA replication dynamics and DNA damage response.

    • Jenni Nikkilä
    • , Ann Christin Parplys
    •  & Robert Winqvist
  • Article |

    Loss of the tumour suppressor Rb1 alone is thought to be insufficient for tumorigenesis. In this study, Liu et al. demonstrate that cells in which all three Rb1 family members are inactivated can initiate tumour formation, but only if cell survival is ensured by the retention of cell–cell contacts.

    • Yongqing Liu
    • , Ester Sánchez-Tilló
    •  & Douglas C. Dean
  • Article |

    Hodgkin’s lymphoma has a genetic component that is poorly understood. In this study, Frampton et al. perform a genome-wide association study in German patients and combine the results with a previously published UK genome-wide association study to identify susceptibility loci at 3p24.1 and 6q23.3.

    • Matthew Frampton
    • , Miguel Inacio da Silva Filho
    •  & Richard S. Houlston
  • Article |

    Non-small cell lung cancers (NSCLC) that harbour mutations in KRas can be separated into KRas-dependent and -independent subsets. By analysing transcriptome, proteome and phosphoproteome data from NSCLC cell lines, Balbin et al. show that KRas-dependent cell lines activate the Lck pathway.

    • O. Alejandro Balbin
    • , John R. Prensner
    •  & Arul M. Chinnaiyan
  • Article
    | Open Access

    Tumour biopsies contain contaminating normal cells and these can influence the analysis of tumour samples. In this study, Yoshihara et al.develop an algorithm based on gene expression profiles from The Cancer Genome Atlas to estimate the number of contaminating normal cells in tumour samples.

    • Kosuke Yoshihara
    • , Maria Shahmoradgoli
    •  & Roel G.W. Verhaak
  • Article
    | Open Access

    Hyaluronan is a component of the tumour extracellular matrix. Here, Chauhan et al. show that hyaluronan increases blood pressure in collagen-rich tumours by compressing vessel walls, and that reducing the level of hyaluranon with an angiotensin II inhibitor increases blood flow and drug penetrance in tumours.

    • Vikash P. Chauhan
    • , John D. Martin
    •  & Rakesh K. Jain
  • Article
    | Open Access

    Viruses contribute to the pathogenesis of certain cancers. Using massively parallel sequencing data from The Cancer Genome Atlas to analyse viral expression in 19 tumour types, Tang et al. both confirm and reject previously described viral associations and present new information on viral integration and host interaction.

    • Ka-Wei Tang
    • , Babak Alaei-Mahabadi
    •  & Erik Larsson