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.

Details

Title
Integrated genetic and epigenetic analysis of myxofibrosarcoma
Author
Ogura, Koichi 1 ; Hosoda, Fumie 2 ; Arai, Yasuhito 2 ; Nakamura, Hiromi 2 ; Hama, Natsuko 2 ; Totoki, Yasushi 2 ; Yoshida, Akihiko 3 ; Nagai, Momoko 2 ; Kato, Mamoru 2 ; Arakawa, Erika 2 ; Mukai, Wakako 2 ; Rokutan, Hirofumi 2 ; Kawai, Akira 4 ; Tanaka, Sakae 5 ; Shibata, Tatsuhiro 6   VIAFID ORCID Logo 

1  Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan; Department of Musculoskeletal Oncology, National Cancer Center Hospital, Tokyo, Japan; Department of Orthopaedic Surgery, The University of Tokyo, Tokyo, Japan 
2  Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan 
3  Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan 
4  Department of Musculoskeletal Oncology, National Cancer Center Hospital, Tokyo, Japan 
5  Department of Orthopaedic Surgery, The University of Tokyo, Tokyo, Japan 
6  Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan; Laboratory of Molecular Medicine, Human Genome Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan 
Pages
1-11
Publication year
2018
Publication date
Jul 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-018-03891-9
ProQuest document ID
2071157943
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.