社区癌症中心的精准医学:肿瘤泛癌DNA/RNA测序揭示临床相关基因融合

S. Darabi, Carlos E. Zuazo, David Braxton, B. Eisenberg, M. Demeure
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摘要

背景:当两个独立的基因通过基因组重排形成一个杂交基因时,就会发生基因融合,这通常会导致编码蛋白的异常表达和功能。在血液学和实体癌中,致瘤融合可能是预后、诊断或治疗性生物标志物。对这种融合的功能影响的更好的检测和理解可能有利于病人的护理。方法:我们对我们的内部基因组数据库进行回顾性分析,以确定在我们社区癌症中心看到的不同实体瘤中已知的和新的基因融合。然后我们研究了我们确定的融合的临床意义。结果:我们在26种不同的癌症类型中鉴定了420个已知的致癌融合和25个未分类的基因融合。在420例已知融合阳性肿瘤中,有366例独特的基因融合。结论:约10%的肿瘤存在致癌融合,这支持了对晚期癌症患者应提供包括RNA测序在内的全面分子谱分析的观点。
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Precision Medicine in a Community Cancer Center: Pan-Cancer DNA/RNA Sequencing of Tumors Reveals Clinically Relevant Gene Fusions
Background: Gene fusions occur when two independent genes form a hybrid gene through genomic rearrangements, which often leads to abnormal expression and function of an encoded protein. In hematological and solid cancers, oncogenic fusions may be prognostic, diagnostic, or therapeutic biomarkers. Improved detection and understanding of the functional implications of such fusions may be beneficial for patient care. Methods: We performed a retrospective analysis of our internal genomic database to identify known and novel gene fusions in different solid tumors seen in our community cancer center. We then investigated the clinical implications of the fusions we identified. Results: We identified 420 known oncogenic fusions and 25 unclassified gene fusions across twenty-six different cancer types. Of 420 fusion-positive tumors with known fusions, there were 366 unique gene fusions. Conclusions: About 10% of tumors investigated had oncogenic fusions, which supports the notion that comprehensive molecular profiling, including RNA sequencing, should be provided for patients with advanced cancers.
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