Improved EGFR mutation detection using combined exosomal RNA and circulating tumor DNA in NSCLC patient plasma.
Improved EGFR mutation detection using combined exosomal RNA and circulating tumor DNA in NSCLC patient plasma.
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DOI：
10.1093/annonc/mdx765
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发表时间：
2018-03-01
期刊：
影响因子：
--
通讯作者：
Skog J
中科院分区：
文献类型：
--
作者：
Krug AK;Enderle D;Karlovich C;Priewasser T;Bentink S;Spiel A;Brinkmann K;Emenegger J;Grimm DG;Castellanos-Rizaldos E;Goldman JW;Sequist LV;Soria JC;Camidge DR;Gadgeel SM;Wakelee HA;Raponi M;Noerholm M;Skog J
用于体细胞突变检测的循环肿瘤DNA（ctDNA）的主要限制是在癌症患者的子集中发现的低水平的ctDNA。我们研究了使用外泌体RNA（exoRNA）和无细胞DNA（cfDNA）的联合分离是否可以改善非小细胞肺癌（NSCLC）患者中EGFR突变检测的血液液体活检。从入组TIGER-X（NCT 01526928）的84例患者中采集匹配的治疗前肿瘤和血浆，TIGER-X是一项在突变型EGFR NSCLC患者中进行的rociletinib I/II期研究。使用靶向的下一代测序板（EXO 1000）对合并的分离的exoRNA和cfDNA（exoNA）进行突变盲分析，并使用通过BEAMing的ctDNA分析与来自相同样品的现有数据进行比较。对于exoNA，检测激活EGFR突变的灵敏度为98%，检测EGFR T790 M的灵敏度为90%。通过BEAMing对ctDNA的相应灵敏度对于激活突变为82%，对于T790 M为84%。在胸内转移性疾病患者亚组（M0/M1a; n = 21）中，当使用exoNA进行检测时，激活突变的灵敏度从26%增加到74%（P = 0.003），T790 M的灵敏度从19%增加到31%（P = 0.5）。exoRNA和ctDNA的组合增加了血浆中EGFR突变检测的灵敏度，在已知ctDNA水平低的M0/M1a疾病患者亚组中观察到最大的改善，并对单独ctDNA的突变检测提出了挑战。NCT01526928
A major limitation of circulating tumor DNA (ctDNA) for somatic mutation detection has been the low level of ctDNA found in a subset of cancer patients. We investigated whether using a combined isolation of exosomal RNA (exoRNA) and cell-free DNA (cfDNA) could improve blood-based liquid biopsy for EGFR mutation detection in non-small-cell lung cancer (NSCLC) patients. Matched pretreatment tumor and plasma were collected from 84 patients enrolled in TIGER-X (NCT01526928), a phase 1/2 study of rociletinib in mutant EGFR NSCLC patients. The combined isolated exoRNA and cfDNA (exoNA) was analyzed blinded for mutations using a targeted next-generation sequencing panel (EXO1000) and compared with existing data from the same samples using analysis of ctDNA by BEAMing. For exoNA, the sensitivity was 98% for detection of activating EGFR mutations and 90% for EGFR T790M. The corresponding sensitivities for ctDNA by BEAMing were 82% for activating mutations and 84% for T790M. In a subgroup of patients with intrathoracic metastatic disease (M0/M1a; n = 21), the sensitivity increased from 26% to 74% for activating mutations (P = 0.003) and from 19% to 31% for T790M (P = 0.5) when using exoNA for detection. Combining exoRNA and ctDNA increased the sensitivity for EGFR mutation detection in plasma, with the largest improvement seen in the subgroup of M0/M1a disease patients known to have low levels of ctDNA and poses challenges for mutation detection on ctDNA alone. NCT01526928
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影响因子：
3.7
作者：
Enderle D;Spiel A;Coticchia CM;Berghoff E;Mueller R;Schlumpberger M;Sprenger-Haussels M;Shaffer JM;Lader E;Skog J;Noerholm M
通讯作者：
Noerholm M
影响因子：
3.6
作者：
Lokhandwala, Tasneem;Bittoni, Marisa A.;Carbone, David P.
通讯作者：
Carbone, David P.
DOI：
10.1073/pnas.0507904102
发表时间：
2005-11-08
影响因子：
11.1
作者：
Diehl, F;Li, M;Vogelstein, B
通讯作者：
Vogelstein, B
影响因子：
11.5
作者：
Danila, Daniel C.;Heller, Glenn;Scher, Howard I.
通讯作者：
Scher, Howard I.
DOI：
10.1158/1078-0432.ccr-15-1260
发表时间：
2016-05-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Karlovich C;Goldman JW;Sun JM;Mann E;Sequist LV;Konopa K;Wen W;Angenendt P;Horn L;Spigel D;Soria JC;Solomon B;Camidge DR;Gadgeel S;Paweletz C;Wu L;Chien S;O'Donnell P;Matheny S;Despain D;Rolfe L;Raponi M;Allen AR;Park K;Wakelee H
通讯作者：
Wakelee H