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对一万多个晚期实体瘤进行全面基因组分析。

Comprehensive genomic profiling of over 10,000 advanced solid tumors.

作者信息

De La O Jean-Paul, Hoag Jess R, Deem Angela K, Wang Min, Starodynov Arthur, Udhane Sameer S, LoBello Janine R, Therala Nishitha, Hall David W, Basu Gargi D, Baehner Frederick L

机构信息

Exact Sciences Corporation, Madison, WI 53719, USA.

出版信息

Oncotarget. 2025 Jul 25;16:587-603. doi: 10.18632/oncotarget.28757.

Abstract

PURPOSE

To summarize clinically relevant genomic alterations in solid tumor samples from over 10,000 patients.

METHODS

Descriptive statistics were used to summarize findings of retrospectively analyzed OncoExTra assay data from solid tumor samples.

RESULTS

The analysis cohort included 11,091 solid tumor samples from 10,768 patients. Therapeutically actionable alterations were present in 92.0% of patient samples. Biomarkers associated with on- or off-label FDA-approved therapies were detected in 29.2% and 28.0% of samples, respectively. The prevalence of hotspot alterations detected at variant allele frequency (VAF) <5% was analyzed among 7,481 samples (67.5%) harboring ≥1 of these events: 13.7% (1,022 of 7,481) had ≥1 alteration detected at VAF <5%, and 9.8% (558 of 5,690) of hotspot alterations associated with an on- or off-label FDA-approved therapy were detected at VAF <5%. Common and rare mutations in the promoter were found in 8.4% (933) of samples. Whole transcriptome sequencing detected clinically relevant fusions in 7.5% of samples, with highest frequencies in prostate cancer (42.0%). The transcript was found in 14 NSCLC samples (2.7%).

CONCLUSIONS

The broad capabilities of the OncoExTra assay detected therapeutically actionable and other clinically relevant genomic events that can inform clinical decision-making for patients with advanced solid tumors.

摘要

目的

总结来自10000多名患者的实体瘤样本中具有临床相关性的基因组改变。

方法

采用描述性统计方法总结对实体瘤样本进行回顾性分析的OncoExTra检测数据的结果。

结果

分析队列包括来自10768名患者的11091份实体瘤样本。92.0%的患者样本中存在可用于治疗的改变。分别在29.2%和28.0%的样本中检测到与FDA批准的治疗药物的标签上或标签外使用相关的生物标志物。在7481份(67.5%)具有≥1个此类事件的样本中,分析了在变异等位基因频率(VAF)<5%时检测到的热点改变的发生率:13.7%(7481份中的1022份)在VAF<5%时检测到≥1个改变,与FDA批准的治疗药物的标签上或标签外使用相关的热点改变中有9.8%(5690份中的558份)在VAF<5%时被检测到。在8.4%(933份)的样本中发现启动子区存在常见和罕见突变。全转录组测序在7.5%的样本中检测到具有临床相关性的融合,在前列腺癌中频率最高(42.0%)。在14份非小细胞肺癌样本(2.7%)中发现了该转录本。

结论

OncoExTra检测的广泛功能检测到了具有治疗意义和其他临床相关的基因组事件,可为晚期实体瘤患者的临床决策提供依据。

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