The landscape of genetic aberrations in myxofibrosarcoma

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

The landscape of genetic aberrations in myxofibrosarcoma

Tools

Preview	PDF (Original Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader 2MB
	Other (Supporting Information) 21MB

Item Type:	Article
Title:	The landscape of genetic aberrations in myxofibrosarcoma
Creators Name:	Takeuchi, Y., Yoshida, K., Halik, A., Kunitz, A., Suzuki, H., Kakiuchi, N., Shiozawa, Y., Yokoyama, A., Inoue, Y., Hirano, T., Yoshizato, T., Aoki, K., Fujii, Y., Nannya, Y., Makishima, H., Pfitzner, B.M., Bullinger, L., Hirata, M., Jinnouchi, K., Shiraishi, Y., Chiba, K., Tanaka, H., Miyano, S., Okamoto, T., Haga, H., 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

Repository Staff Only: item control page

Download Statistics

Downloads

Downloads per month over past year