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The landscape of genetic aberrations in myxofibrosarcoma

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Item Type:Article
Title:The landscape of genetic aberrations in myxofibrosarcoma
Creators Name:Takeuchi, Y. and Yoshida, K. and Halik, A. and Kunitz, A. and Suzuki, H. and Kakiuchi, N. and Shiozawa, Y. and Yokoyama, A. and Inoue, Y. and Hirano, T. and Yoshizato, T. and Aoki, K. and Fujii, Y. and Nannya, Y. and Makishima, H. and Pfitzner, B.M. and Bullinger, L. and Hirata, M. and Jinnouchi, K. and Shiraishi, Y. and Chiba, K. and Tanaka, H. and Miyano, S. and Okamoto, T. and Haga, H. and Ogawa, S. and Damm, F.
Abstract: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.
Keywords:Druggable Alterations, Genetics, Myxofibrosarcoma, Whole Genome/Exome/Targeted-Capture Sequence
Source:International Journal of Cancer
ISSN:0020-7136
Publisher:Wiley
Volume:151
Number:4
Page Range:565-577
Date:15 August 2022
Official Publication:https://doi.org/10.1002/ijc.34051
PubMed:View item in PubMed

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