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| Open AccessIntegrated genetic and epigenetic analysis of myxofibrosarcoma
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
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Article
| Open AccessIntegrative genomic and transcriptomic analysis of leiomyosarcoma
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
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Article
| Open AccessGeneration and comparison of CRISPR-Cas9 and Cre-mediated genetically engineered mouse models of sarcoma
Site-specific recombination and CRISPR-Cas9 have been used to generate genetically engineered mouse models of cancer. Here the authors compare sarcomas generated using both systems and see similar genetic and cellular phenotypes, suggesting CRISPR-Cas9 can be used to rapidly generate sarcoma models.
- Jianguo Huang
- , Mark Chen
- & David G. Kirsch
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Article
| Open AccessMAX inactivation is an early event in GIST development that regulates p16 and cell proliferation
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
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Article
| Open AccessTP53 mutations emerge with HDM2 inhibitor SAR405838 treatment in de-differentiated liposarcoma
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
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Article
| Open AccessEpigenetic re-expression of HIF-2α suppresses soft tissue sarcoma growth
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
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Article
| Open AccessA mutation in the POT1 gene is responsible for cardiac angiosarcoma in TP53-negative Li–Fraumeni-like families
Genetic factors that cause cardiac angiosarcoma are unknown. Calveteet al. show that a missense mutation in protection of telomeres1 (POT1) gene causes cardiac angiosarcoma by affecting the POT1 function and, consequently, telomere length and stability.
- Oriol Calvete
- , Paula Martinez
- & Javier Benítez
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Article
| Open AccessIntegrated genetic and epigenetic analysis defines novel molecular subgroups in rhabdomyosarcoma
Rhabdomyosarcoma is a common childhood soft-tissue cancer. Here Seki and Nishimura analyse the exome, transcriptome, copy number and DNA methylome of 60 sarcomas and identify distinct methylation subgroups associated with genetic and clinical features.
- Masafumi Seki
- , Riki Nishimura
- & Junko Takita
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Rb1 family mutation is sufficient for sarcoma initiation
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