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The landscape of genetic aberrations in myxofibrosarcoma

Takeuchi, Yasuhide Yoshida, Kenichi Halik, Adriane Kunitz, Annegret Suzuki, Hiromichi Kakiuchi, Nobuyuki Shiozawa, Yusuke Yokoyama, Akira Inoue, Yoshikage Hirano, Tomonori Yoshizato, Tetsuichi Aoki, Kosuke Fujii, Yoichi Nannya, Yasuhito Makishima, Hideki Pfitzner, Berit Maria Bullinger, Lars Hirata, Masahiro Jinnouchi, Keita Shiraishi, Yuichi Chiba, Kenichi Tanaka, Hiroko Miyano, Satoru Okamoto, Takeshi Haga, Hironori Ogawa, Seishi Damm, Frederik 京都大学 DOI:10.1002/ijc.34051

2022.08.15

概要

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. Our study highlights the genetic complexity underlying sarcomagenesis of MFS.

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