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Integrated molecular characterization of adult soft tissue sarcoma for therapeutic targets.


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.

SUBMITTER: Kim J 

PROVIDER: S-EPMC6311917 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Integrated molecular characterization of adult soft tissue sarcoma for therapeutic targets.

Kim Jihyun J   Kim June Hyuk JH   Kang Hyun Guy HG   Park Seog Yun SY   Yu Jung Yeon JY   Lee Eun Young EY   Oh Sung Eun SE   Kim Young Ho YH   Yun Tak T   Park Charny C   Cho Soo Young SY   You Hye Jin HJ  

BMC medical genetics 20181231 Suppl 1


<h4>Background</h4>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 prof  ...[more]

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