Detection of tumor PIK3CA status in metastatic breast cancer using peripheral blood.
Detection of tumor PIK3CA status in metastatic breast cancer using peripheral blood.
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DOI：
10.1158/1078-0432.ccr-11-2696
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发表时间：
2012-06-15
期刊：
影响因子：
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通讯作者：
Park BH
中科院分区：
文献类型：
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作者：
Higgins MJ;Jelovac D;Barnathan E;Blair B;Slater S;Powers P;Zorzi J;Jeter SC;Oliver GR;Fetting J;Emens L;Riley C;Stearns V;Diehl F;Angenendt P;Huang P;Cope L;Argani P;Murphy KM;Bachman KE;Greshock J;Wolff AC;Park BH
我们试图评估使用称为BEAMing的新技术检测来自转移性乳腺癌患者血浆的循环肿瘤DNA（ctDNA）中的PIK 3CA突变的可行性。在一项回顾性分析中，通过BEAMing筛选了49份来自乳腺癌患者的肿瘤和时间匹配的血浆样本的PIK 3CA突变。然后，我们通过BEAMing前瞻性筛选了60例转移性乳腺癌患者的ctDNA中的PIK 3CA突变，并将结果与通过使用测序和BEAMing筛选相应的存档肿瘤组织DNA获得的结果进行了比较。两个患者队列中BEAMing检测的PIK 3CA突变的总体频率相似（分别为29%和28.3%）。在回顾性队列中，福尔马林固定、石蜡包埋（FFPE）样本和时间匹配血浆ctDNA之间通过BEAMing检测的PIK 3CA突变状态一致性为100%（34/34）。在前瞻性队列中，51例可评价病例中，ctDNA BEAMing与存档肿瘤组织DNA测序的一致率为72.5%。当通过测序和BEAMing筛选相同存档组织DNA的PIK 3CA突变时（n = 41个组织样品），获得的结果具有100%的一致性。分析血浆来源的ctDNA用于检测转移性乳腺癌患者中的PIK 3CA突变是可行的。我们的研究结果表明，PIK 3CA突变状态可以改变疾病复发，强调重新评估PIK 3CA状态的重要性当代（非档案）生物标本。这些结果对靶向治疗反应的预测性生物标志物的开发具有意义。
We sought to evaluate the feasibility of detecting PIK3CA mutations in circulating tumor DNA (ctDNA) from plasma of patients with metastatic breast cancer using a novel technique called BEAMing. In a retrospective analysis, 49 tumor and temporally matched plasma samples from patients with breast cancer were screened for PIK3CA mutations by BEAMing. We then prospectively screened the ctDNA of 60 patients with metastatic breast cancer for PIK3CA mutations by BEAMing and compared the findings with results obtained by screening corresponding archival tumor tissue DNA using both sequencing and BEAMing. The overall frequency of PIK3CA mutations by BEAMing was similar in both patient cohorts (29% and 28.3%, respectively). In the retrospective cohort, the concordance of PIK3CA mutation status by BEAMing between formalin-fixed, paraffin-embedded (FFPE) samples and ctDNA from temporally matched plasma was 100% (34 of 34). In the prospective cohort, the concordance rate among 51 evaluable cases was 72.5% between BEAMing of ctDNA and sequencing of archival tumor tissue DNA. When the same archival tissue DNA was screened by both sequencing and BEAMing for PIK3CA mutations (n = 41 tissue samples), there was 100% concordance in the obtained results. Analysis of plasma-derived ctDNA for the detection of PIK3CA mutations in patients with metastatic breast cancer is feasible. Our results suggest that PIK3CA mutational status can change upon disease recurrence, emphasizing the importance of reassessing PIK3CA status on contemporary (not archival) biospecimens. These results have implications for the development of predictive biomarkers of response to targeted therapies.