Division of Urology, Department of Surgery, Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, Australia,
Clin Exp Metastasis. 2014 Feb;31(2):159-67. doi: 10.1007/s10585-013-9617-2. Epub 2013 Oct 2.
Personalised oncology through mutational profiling of cancers requires the procurement of fresh frozen tumour samples for genomics applications. While primary cancers are often surgically excised and therefore yield such tissue, metastases in the setting of a known cancer diagnosis are not routinely sampled prior to systemic therapy. Our study aimed to determine the suitability of extracted nucleic acids for genomics applications using distant metastatic prostate cancer samples obtained via percutaneous or surgical biopsy. Patients with metastatic prostate cancer were recruited for image-guided biopsy of metastases. Patients undergoing surgical procedures for the complications of metastases were also recruited. Tissue samples were flash frozen and cryosectioned for histological examination. DNA and RNA were simultaneously extracted and genomic DNA hybridised onto SNP arrays for genome-wide copy number analysis. 37 samples of metastatic tissue from seven patients with prostate cancer were obtained. Five of these underwent image-guided biopsies whilst two had therapeutic surgical procedures performed. 22 biopsy samples were obtained across the image-guided biopsy patients with 80 % of samples being successfully processed for downstream analysis. Nucleic acid yield from these samples were satisfactory for genomics applications. Copy number analysis revealed a median estimated tumour purity of 53 % and all samples showed chromosomal abnormalities suggestive of malignancy. The procurement of osseous metastatic prostate cancer from live patients, including the use of image-guided biopsy, is safe and feasible. Sufficient tissue can be obtained in a manner such that extracted nucleic acids are suitable for genomics research.
通过对癌症的突变分析进行个体化肿瘤学研究,需要采集新鲜冷冻的肿瘤样本进行基因组学应用。虽然原发性癌症通常通过手术切除,因此可以获得这种组织,但在已知癌症诊断的情况下,转移灶在系统性治疗之前通常不会进行采样。我们的研究旨在确定使用经皮或手术活检获得的远处转移性前列腺癌样本进行基因组学应用的提取核酸的适用性。招募患有转移性前列腺癌的患者进行转移灶的影像学引导活检。还招募了因转移灶并发症而接受手术治疗的患者。组织样本经快速冷冻并冷冻切片进行组织学检查。同时提取 DNA 和 RNA,并将基因组 DNA 杂交到 SNP 芯片上进行全基因组拷贝数分析。从 7 名前列腺癌患者的 37 个转移性组织样本中获得。其中 5 名患者接受了影像学引导活检,2 名患者接受了治疗性手术。在接受影像学引导活检的患者中获得了 22 个活检样本,80%的样本成功进行了下游分析。这些样本的核酸产量足以满足基因组学应用的需要。拷贝数分析显示,中位数估计肿瘤纯度为 53%,所有样本均显示染色体异常,提示恶性肿瘤。从活患者中获取骨转移性前列腺癌,包括使用影像学引导活检,是安全可行的。可以以提取的核酸适合基因组学研究的方式获得足够的组织。