Sarcoma

  • Article
    | Open Access

    Heterogeneity in leiomyosarcomas (LMS) makes treatment of the disease challenging. Here the authors analyze LMS heterogeneity and molecular LMS subtypes using genomics and transcriptomics, finding origins in distinct lineages and associations with survival, in addition to the early emergence of metastatic clones.

    • Nathaniel D. Anderson
    • , Yael Babichev
    •  & Adam Shlien
  • Article
    | Open Access

    Sarcomas are morphologically heterogeneous tumours rendering their classification challenging. Here the authors developed a classifier using DNA methylation data from several soft tissue and bone sarcoma subtypes, which has the potential to improve classification for research and clinical purposes.

    • Christian Koelsche
    • , Daniel Schrimpf
    •  & Andreas von Deimling
  • Article
    | Open Access

    Rhabdomyosarcomas are tumours blocked in myogenic differentiation, which despite the expression of master muscle regulatory factors, including MYOD, are unable to differentiate. Here, the authors show that SNAI2 is upregulated by MYOD through super enhancers, binds to MYOD target enhancers, and arrests differentiation.

    • Silvia Pomella
    • , Prethish Sreenivas
    •  & Myron S. Ignatius
  • Article
    | Open Access

    Promising results of cancer therapies in transplant tumor models often fail to predict efficacy in clinical trials. Here the authors show that, while transplant tumors are cured by radiotherapy and PD-1 blockade, autochthonous sarcomas are resistant to the identical treatment, recapitulating the immune landscape and resistance to checkpoint blockade observed in most sarcoma patients.

    • Amy J. Wisdom
    • , Yvonne M. Mowery
    •  & David G. Kirsch
  • Article
    | Open Access

    Chondrosarcomas are frequently aggressive, understanding the transcriptional changes associated with progression may help in developing new treatments. Here, the authors show that HIF-2α is increased in expression on progression and pharmacological inhibition of the protein together with chemotherapy is a useful strategy for controlling tumour growth in mice.

    • Hyeonkyeong Kim
    • , Yongsik Cho
    •  & Jin-Hong Kim
  • Article
    | Open Access

    Osteosarcoma is an aggressive tumour and little is known the mechanisms underpinning its highly metastatic nature. Here, the authors highlight a role for the CK1α/CBX4 axis in driving metastasis, suggesting that this pathway might be targeted for therapeutic benefit.

    • Xin Wang
    • , Ge Qin
    •  & Tiebang Kang
  • Article
    | Open Access

    Glutamine is an energetic source required for the proliferation of cancer cells. Here, the authors show that soft tissue sarcomas expressing high levels of glutaminase (GLS) are particularly sensitive to glutamine starvation and GLS inhibition in tumour-bearing allograft and autochthonous mouse models.

    • Pearl Lee
    • , Dania Malik
    •  & M. Celeste Simon
  • Article
    | Open Access

    Understanding the genomic features of dedifferentiated liposarcoma (DDLPS) is likely to uncover new options for management. Here, the authors reveal three prognostic groups, and highlight molecular markers associated with malignant transformation.

    • Makoto Hirata
    • , Naofumi Asano
    •  & Koichi Matsuda
  • Article
    | Open Access

    Interactions between germline variants and somatic mutations is a relatively unexplored topic in cancer. Here, in Ewing sarcoma, the authors show that binding of the oncogenic EWSR1-FLI1 fusion transcription factor to a polymorphic enhancer-like DNA element controls MYBL2, whose high expression correlates with prognosis.

    • Julian Musa
    • , Florencia Cidre-Aranaz
    •  & Thomas G. P. Grünewald
  • Article
    | Open Access

    Sarcomas are rare malignant tumours of bone and soft tissue whose diagnosis remain difficult. Here, the authors analyse serum samples from over 1000 patients and using separate discovery, training and validation cohorts, identify and validate a 7-microRNA index that distinguishes malignant sarcomas from benign disease.

    • Naofumi Asano
    • , Juntaro Matsuzaki
    •  & Takahiro Ochiya
  • Article
    | Open Access

    Hofvander and colleagues compare the patterns of clonal evolution in different pathogenetic subgroups of sarcoma. They show that sarcomas driven by gene fusion or amplification display few additional changes over time, whereas sarcomas with complex karyotypes show a gradual increase of nucleotide- and chromosome-level mutations.

    • Jakob Hofvander
    • , Björn Viklund
    •  & Fredrik Mertens
  • Article
    | Open Access

    Granular cell tumors (GCTs) are rare tumors that arise in multiple anatomical locations. Here, the authors investigate the genomics of GCTs, finding inactivating somatic mutations in ATP6AP1 or ATP6AP2 in 72% of the 82 GCTs analyzed. In vitro manipulation of these genes recapitulated GCT phenotypes in cellular models.

    • Fresia Pareja
    • , Alissa H. Brandes
    •  & Jorge S. Reis-Filho
  • Article
    | Open Access

    Myxofibrosarcoma occurs in adults and is associated with high local relapse. Here, based on exome/transcriptome sequencing and DNA methylation analysis, the authors identify driver genes and methylation clusters associated with unique combinations of mutations, outcomes, and immune cell compositions.

    • Koichi Ogura
    • , Fumie Hosoda
    •  & Tatsuhiro Shibata
  • Article
    | Open Access

    The molecular genetic landscape of leiomyosarcoma (LMS) is largely unknown. Here, the authors identify frequent DNA copy number alterations, whole-genome duplication, TP53 and RB1 inactivation, alternative telomere lengthening, and genomic imprints of defective DNA repair via homologous recombination as a potential therapeutic target in LMS patients.

    • Priya Chudasama
    • , Sadaf S. Mughal
    •  & Stefan Fröhling
  • Article
    | Open Access

    In gastrointestinal stromal tumours early mutations in known genes are frequently followed by chromosome 14q deletion. Here the authors find mutations resulting in loss of MAX protein expression conserved between primary tumours and metastases in the same patients, suggesting thatMAXmutation is an early event.

    • Inga-Marie Schaefer
    • , Yuexiang Wang
    •  & Jonathan A. Fletcher
  • Article
    | Open Access

    Pre-clinical studies have shown that TP53 mutations can account for acquired resistance to HDM2 antagonists. This study provides clinical evidence for the emergence of TP53mutations in circulating cell-free DNA, seen in 5 out of 20 de-differentiated liposarcoma patients treated with an HDM2 antagonist.

    • Joonil Jung
    • , Joon Sang Lee
    •  & James Watters
  • Article
    | Open Access

    Hypoxia is a common feature of soft tissue sarcomas, resulting in the activation of HIF-1α, which promotes metastasis. Here, Nakazawa et al. show that paradoxically HIF-2α is epigenetically silenced during the progression of multiple sarcoma subtypes, and when reexpressed, blocks tumour growth in vivo.

    • Michael S. Nakazawa
    • , T. S. Karin Eisinger-Mathason
    •  & M. Celeste Simon
  • 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