Tumor-associated copy number changes in the circulation of patients with prostate cancer identified through whole-genome sequencing.
Tumor-associated copy number changes in the circulation of patients with prostate cancer identified through whole-genome sequencing.
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DOI：
10.1186/gm434
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发表时间：
2013
期刊：
影响因子：
12.3
通讯作者：
Speicher MR
中科院分区：
文献类型：
--
作者：
Heitzer E;Ulz P;Belic J;Gutschi S;Quehenberger F;Fischereder K;Benezeder T;Auer M;Pischler C;Mannweiler S;Pichler M;Eisner F;Haeusler M;Riethdorf S;Pantel K;Samonigg H;Hoefler G;Augustin H;Geigl JB;Speicher MR
前列腺癌患者可能会出现转移性或复发性疾病，尽管最初的治愈治疗。转移性前列腺癌扩散到骨的倾向限制了肿瘤沉积物的重复采样。因此，对这种致命的转移性疾病的了解相当少，因为它不常被研究。在这里，我们探索了血浆DNA的全基因组测序，以非侵入性地扫描这些患者的肿瘤基因组。我们希望从血浆DNA中进行全基因组分析，使其适合临床常规应用，并开发了一种基于台式高通量平台的方法，即Illuminas MiSeq仪器。我们以浅测序深度从血浆进行全基因组测序，以在2天内以低成本建立肿瘤的全基因组拷贝数谱。同时，我们对一组55个高兴趣基因和38个内含子进行了测序，这些基因具有频繁的融合断点，例如具有高覆盖率的TMPRSS2-ERG融合。在对我们的方法进行了来自25名无癌症个体的样本的密集测试后，我们分析了来自5名去势抵抗性（CRPC）患者和4名去势敏感性前列腺癌（CSPC）患者的13份血浆样本。我们的患者血浆中的全基因组分析揭示了多个拷贝数畸变，包括先前在前列腺肿瘤中报道的那些，例如8p的丢失和8q的增加。在CRPC患者中观察到AR基因座的高水平拷贝数增加，但在CSPC疾病患者中未观察到。我们鉴定了TMPRSS2-ERG重排相关的21号染色体上3-Mbp缺失，并在这些病例中发现了相应的融合血浆片段。在一个索引情况下，原发性肿瘤的多区域测序确定了每个扇区中不同的拷贝数变化，表明多灶性疾病。我们对该指示病例的血浆分析是在原发性肿瘤切除后13年进行的，显示了新型染色体重排，这些重排在9个月内的系列血浆分析中保持稳定，这与一个转移性克隆的存在一致。前列腺癌的基因组图谱可以通过非侵入性手段从血浆DNA建立。我们的方法在2天内提供了特定的基因组特征，因此可以作为“液体活检”。
Patients with prostate cancer may present with metastatic or recurrent disease despite initial curative treatment. The propensity of metastatic prostate cancer to spread to the bone has limited repeated sampling of tumor deposits. Hence, considerably less is understood about this lethal metastatic disease, as it is not commonly studied. Here we explored whole-genome sequencing of plasma DNA to scan the tumor genomes of these patients non-invasively. We wanted to make whole-genome analysis from plasma DNA amenable to clinical routine applications and developed an approach based on a benchtop high-throughput platform, that is, Illuminas MiSeq instrument. We performed whole-genome sequencing from plasma at a shallow sequencing depth to establish a genome-wide copy number profile of the tumor at low costs within 2 days. In parallel, we sequenced a panel of 55 high-interest genes and 38 introns with frequent fusion breakpoints such as the TMPRSS2-ERG fusion with high coverage. After intensive testing of our approach with samples from 25 individuals without cancer we analyzed 13 plasma samples derived from five patients with castration resistant (CRPC) and four patients with castration sensitive prostate cancer (CSPC). The genome-wide profiling in the plasma of our patients revealed multiple copy number aberrations including those previously reported in prostate tumors, such as losses in 8p and gains in 8q. High-level copy number gains in the AR locus were observed in patients with CRPC but not with CSPC disease. We identified the TMPRSS2-ERG rearrangement associated 3-Mbp deletion on chromosome 21 and found corresponding fusion plasma fragments in these cases. In an index case multiregional sequencing of the primary tumor identified different copy number changes in each sector, suggesting multifocal disease. Our plasma analyses of this index case, performed 13 years after resection of the primary tumor, revealed novel chromosomal rearrangements, which were stable in serial plasma analyses over a 9-month period, which is consistent with the presence of one metastatic clone. The genomic landscape of prostate cancer can be established by non-invasive means from plasma DNA. Our approach provides specific genomic signatures within 2 days which may therefore serve as 'liquid biopsy'.
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影响因子：
11.2
作者：
Attard, Gerhardt;Swermenhuis, Joost F.;de Bono, Johann S.
通讯作者：
de Bono, Johann S.
影响因子：
50.3
作者：
Chen M;Pratt CP;Zeeman ME;Schultz N;Taylor BS;O'Neill A;Castillo-Martin M;Nowak DG;Naguib A;Grace DM;Murn J;Navin N;Atwal GS;Sander C;Gerald WL;Cordon-Cardo C;Newton AC;Carver BS;Trotman LC
通讯作者：
Trotman LC
影响因子：
2.4
作者：
Fiorentino, Michelangelo;Capizzi, Elisa;Loda, Massimo
通讯作者：
Loda, Massimo
影响因子：
11.2
作者：
Heitzer, Ellen;Auer, Martina;Speicher, Michael R.
通讯作者：
Speicher, Michael R.
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