Integrated molecular characterization of adult soft tissue sarcoma for therapeutic targets

• Main Authors: Jihyun Kim, June Hyuk Kim, Hyun Guy Kang, Seog Yun Park, Jung Yeon Yu, Eun Young Lee, Sung Eun Oh, Young Ho Kim, Tak Yun, Charny Park, Soo Young Cho, Hye Jin You
• Format: Article
• Language: English
• Published: BMC 2018-12-01
• Series: BMC Medical Genetics
• Subjects: Complex karyotype sarcoma; Molecular characterization; PDGFRA; CDK4 and RB1
• Online Access: http://link.springer.com/article/10.1186/s12881-018-0722-6

Abstract Background Several studies have investigated the molecular drivers and therapeutic targets in adult soft tissue sarcomas. However, such studies are limited by the genomic heterogeneity and rarity of sarcomas, particularly in those with complex and unbalanced karyotypes. Additional biomarkers are needed across sarcoma types to improve therapeutic strategies. To investigate the molecular characteristics of complex karyotype sarcomas (CKSs) for therapeutic targets, we performed genomic profiling. Results The mutational landscape showed that TP53, ATRX, and PTEN genes were highly mutated. CKS samples were categorized into three groups based on copy number variations that were associated with CDK4 and RB1 signatures. Integrated analysis of genomic and transcriptomic data revealed several pathways related to PDGFR, which could be a strategic target for anti-sarcoma therapy. Conclusions This study provides a detailed molecular classification of CKSs and proposes several therapeutic targets. Targeted or combinational therapies for treating CKS should be considered before chemotherapy.