Integrated genetic and epigenetic analysis of myxofibrosarcoma.

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 Commun

journal_title

Nature communications

authors

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 T

doi

10.1038/s41467-018-03891-9

subject

Has Abstract

pub_date

2018-07-17 00:00:00

pages

2765

issue

1

issn

2041-1723

pii

10.1038/s41467-018-03891-9

journal_volume

9

pub_type

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