The driver landscape of sporadic chordoma
Open Access
- 11 October 2017
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 8 (1), 1-6
- https://doi.org/10.1038/s41467-017-01026-0
Abstract
Chordoma is a malignant, often incurable bone tumour showing notochordal differentiation. Here, we defined the somatic driver landscape of 104 cases of sporadic chordoma. We reveal somatic duplications of the notochordal transcription factor brachyury (T) in up to 27% of cases. These variants recapitulate the rearrangement architecture of the pathogenic germline duplications of T that underlie familial chordoma. In addition, we find potentially clinically actionable PI3K signalling mutations in 16% of cases. Intriguingly, one of the most frequently altered genes, mutated exclusively by inactivating mutation, was LYST (10%), which may represent a novel cancer gene in chordoma.This publication has 26 references indexed in Scilit:
- Signatures of mutational processes in human cancerNature, 2013
- An integrated functional genomics approach identifies the regulatory network directed by brachyury (T) in chordomaThe Journal of Pathology, 2012
- deFuse: An Algorithm for Gene Fusion Discovery in Tumor RNA-Seq DataPLoS Computational Biology, 2011
- Recurrent Chromosomal Copy Number Alterations in Sporadic ChordomasPLOS ONE, 2011
- Role of the transcription factor T (brachyury) in the pathogenesis of sporadic chordoma: a genetic and functional‐based studyThe Journal of Pathology, 2010
- Analysis of receptor tyrosine kinases (RTKs) and downstream pathways in chordomasNeuro-Oncology, 2010
- T (brachyury) gene duplication confers major susceptibility to familial chordomaNature Genetics, 2009
- Response to imatinib plus sirolimus in advanced chordomaAnnals Of Oncology, 2009
- Potential therapeutic targets for chordoma: PI3K/AKT/TSC1/TSC2/mTOR pathwayBritish Journal of Cancer, 2009
- TopHat: discovering splice junctions with RNA-SeqBioinformatics, 2009