Abstract:
:Myxofibrosarcoma (MFS) is a common adult soft tissue sarcoma characterized by an infiltrative growth pattern and a high local recurrence rate. Here we report the genetic and epigenetic landscape of MFS based on the results of whole-exome sequencing (N = 41), RNA sequencing (N = 29), and methylation analysis (N = 41), using 41 MFSs as a discovery set, and subsequent targeted sequencing of 140 genes in the entire cohort of 99 MFSs and 17 MFSs' data from TCGA. Fourteen driver genes are identified, including potentially actionable therapeutic targets seen in 37% of cases. There are frequent alterations in p53 signaling (51%) and cell cycle checkpoint genes (43%). Other conceivably actionable driver genes including ATRX, JAK1, NF1, NTRK1, and novel oncogenic BRAF fusion gene are identified. Methylation patterns cluster into three subtypes associated with unique combinations of driver mutations, clinical outcomes, and immune cell compositions. Our results provide a valuable genomic resource to enable the design of precision medicine for MFS.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Ogura K,Hosoda F,Arai Y,Nakamura H,Hama N,Totoki Y,Yoshida A,Nagai M,Kato M,Arakawa E,Mukai W,Rokutan H,Kawai A,Tanaka S,Shibata Tdoi
10.1038/s41467-018-03891-9subject
Has Abstractpub_date
2018-07-17 00:00:00pages
2765issue
1issn
2041-1723pii
10.1038/s41467-018-03891-9journal_volume
9pub_type
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