成人软组织肉瘤治疗靶点的综合分子特征分析
Integrated molecular characterization of adult soft tissue sarcoma for therapeutic targets.
作者信息
Kim Jihyun, Kim June Hyuk, Kang Hyun Guy, Park Seog Yun, Yu Jung Yeon, Lee Eun Young, Oh Sung Eun, Kim Young Ho, Yun Tak, Park Charny, Cho Soo Young, You Hye Jin
机构信息
Clinical Genomic Analysis Branch, Research Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi, 10408, South Korea.
Orthopaedic Oncology Clinic, Hospital, National Cancer Center, Goyang, Gyeonggi, 10408, South Korea.
出版信息
BMC Med Genet. 2018 Dec 31;19(Suppl 1):216. doi: 10.1186/s12881-018-0722-6.
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.
背景
多项研究已对成人软组织肉瘤的分子驱动因素和治疗靶点进行了调查。然而，此类研究受到肉瘤基因组异质性和罕见性的限制，尤其是在那些具有复杂和不平衡核型的肉瘤中。需要跨肉瘤类型的其他生物标志物来改善治疗策略。为了研究复杂核型肉瘤（CKS）的分子特征以寻找治疗靶点，我们进行了基因组分析。
结果
突变图谱显示TP53、ATRX和PTEN基因高度突变。CKS样本根据与CDK4和RB1特征相关的拷贝数变异分为三组。基因组和转录组数据的综合分析揭示了几条与PDGFR相关的通路，这可能是抗肉瘤治疗的一个战略靶点。
结论
本研究提供了CKS的详细分子分类，并提出了几个治疗靶点。在进行化疗之前，应考虑针对CKS的靶向或联合治疗。
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