The landscape of genetic aberrations in myxofibrosarcoma


  • Y. Takeuchi
  • K. Yoshida
  • A. Halik
  • A. Kunitz
  • H. Suzuki
  • N. Kakiuchi
  • Y. Shiozawa
  • A. Yokoyama
  • Y. Inoue
  • T. Hirano
  • T. Yoshizato
  • K. Aoki
  • Y. Fujii
  • Y. Nannya
  • H. Makishima
  • B.M. Pfitzner
  • L. Bullinger
  • M. Hirata
  • K. Jinnouchi
  • Y. Shiraishi
  • K. Chiba
  • H. Tanaka
  • S. Miyano
  • T. Okamoto
  • H. Haga
  • S. Ogawa
  • F. Damm


  • International Journal of Cancer


  • Int J Cancer 151 (4): 565-577


  • Myxofibrosarcoma (MFS) is a rare subtype of sarcoma, whose genetic basis is poorly understood. We analyzed 69 MFS cases using whole-genome (WGS), whole-exome (WES), and/or targeted-sequencing (TS). Newly sequenced genomic data were combined with additional deposited 116 MFS samples. WGS identified a high number of structural variations (SVs) per tumor most frequently affecting the TP53 and RB1 loci, 40% of tumors showed a BRCAness-associated mutation signature, and evidence of chromothripsis was found in all cases. Most frequently mutated /copy number altered genes affected known disease drivers such as TP53 (56.2%), CDKN2A/B (29.7%), RB1 (27.0%), ATRX (19.5%), and HDLBP (18.9%). Several previously unappreciated genetic aberrations including MUC17, FLG, and ZNF780A were identified in more than 20% of patients. Longitudinal analysis of paired diagnosis and relapse time points revealed a 1.2-fold mutation number increase accompanied with substantial changes in clonal composition over time. This study highlights the genetic complexity underlying sarcomagenesis of MFS.