Integrated genetic and epigenetic analysis of myxofibrosarcoma

Nature Communications
Koichi OguraTatsuhiro Shibata

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.

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Citations

May 1, 2020·Frontiers in Oncology·Chiara Caruso, Cecilia Garofalo
Apr 30, 2020·International Journal of Molecular Sciences·Jordan L KohlmeyerDawn E Quelle
Jun 4, 2020·Therapeutic Advances in Medical Oncology·Milena UrbiniMaristella Saponara
Nov 7, 2019·Biomarker Research·Mingzhou GuoJames G Herman
Nov 11, 2020·International Journal of Urology : Official Journal of the Japanese Urological Association·Tetsuya UrasakiShunji Takahashi
Dec 22, 2020·The Journal of Molecular Diagnostics : JMD·Xiu Q WangTorsten O Nielsen
Feb 3, 2019·Surgical Pathology Clinics·Sofia Daniela CarvalhoFrançois Le Loarer
May 6, 2021·The Journal of Pathology. Clinical Research·Iben LyskjaerAdrienne M Flanagan
Jul 6, 2021·European Journal of Histochemistry : EJH·Kazuhiko HashimotoMasao Akagi
Jul 25, 2021·International Journal of Molecular Sciences·Marcella TazzariViviana Vallacchi
May 26, 2020·Oncology Research and Treatment·Andrea SambriGiuseppe Bianchi
Feb 3, 2022·JCO Precision Oncology·Jocelyn Y HsuJames L Chen
Nov 4, 2021·Molecular Cancer Research : MCR·Chantal PauliMark A Rubin

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Datasets Mentioned

BETA
EGAS00001002889
GSE111200

Methods Mentioned

BETA
reverse transcription-PCR
methylation profiling
exome
PCR
chip

Software Mentioned

R package
DNACopy
SPSS
Cutadapt
CIBERSORT
GISTIC
Database for Annotation , Visualization and Integrated Discove...
BWA
Burrows Aligner ( BWA )
BLASTN

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