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首页 » BIOON报道 » Genom Med:全基因组测序技术或可鉴别前列腺癌是否转移或复发

Genom Med:全基因组测序技术或可鉴别前列腺癌是否转移或复发

来源:生物谷 2013-04-08 00:36

2013年4月8日 讯 /生物谷BIOON/ --近日,刊登在国际杂志Genome Medicine上的一篇研究报告中,来自格拉茨医科大学的研究者通过研究揭示,非侵袭性的液体活检可以鉴别出前列腺癌是否转移或者复发,这种检测方法成本较低,比较适用于大多数的医疗保健系统。从血浆DNA的分离来看,前列腺癌的基因组学特性表现为染色体特殊区域的异常拷贝。

在文中研究者表示,甚至有可能对那些激素疗法产生耐药的前列腺癌患者进行区分,激素耐药性的前列腺癌是男性转移性的前列腺癌的一种常见形式。

前列腺癌是男性常见的癌症之一,仅仅在欧洲每年就有260万男性被诊断患有该疾病。PSA检测可在早期对前列腺癌进行检测,尽管运用合适的疗法进行治疗,然而仍然有些男性会发生癌症复发或者癌症转移。

对于癌症的转移进行检测仍然需要不断地活组织检查,研究小组在文中报道了,他们以一种微创的方式来对癌症的复发进行检测。使用血浆DNA的全基因组学分析技术,加上针对前列腺癌的基因靶向测序技术,研究者发现前列腺癌相关的特殊序列存在异常的拷贝数,尽管发生异常的位点比较少,包括序列NCOA2, PHLPP1和TMPRSS2-ERG拷贝数目的错误。

由于每一个患者的癌症特性都存在略微的差异,然而对去势疗法无响应的癌症患者都表现出雄激素受体基因拷贝数的增加。

研究者Jochen Geigl和Michael Speicher教授领导此项研究,他们表示,液体活检技术的开发以及其表现出响应的普遍性和低廉,将使得遗传测试成为一种传统的生检技术。通过测试所得的更多的遗传信息将帮助研究者开发新型的靶向疗法,尤其是针对那些对去势疗法耐药的前列腺癌,而且可以应用于个体化疗法的开发中。(生物谷Bioon.com)

Tumor associated copy number changes in the circulation of patients with prostate cancer identified through whole-genome sequencing

Ellen Heitzer, Peter Ulz, Jelena Belic, Stefan Gutschi, Franz Quehenberger, Katja Fischereder, Theresa Benezeder, Martina Auer, Carina Pischler, Sebastian Mannweiler, Martin Pichler, Florian Eisner, Martin Haeusler, Sabine Riethdorf, Klaus Pantel, Hellmut Samonigg, Gerald Hoefler, Herbert Augustin, Jochen B Geigl and Michael R Speicher

Background 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 noninvasively. Methods 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, i.e. 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 5 patients with castration resistant (CRPC) and 4 patients with castration sensitive prostate cancer (CSPC). Results 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 months period, which is consistent with the presence of one metastatic clone. Conclusions 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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