Abstract
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.
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Meyerson M, Gabriel S, Getz G (2010) Advances in understanding cancer genomes through second-generation sequencing. Nat Rev Genet 11(10):685–696
Macconaill LE, Garraway LA (2010) Clinical implications of the cancer genome. J Clin Oncol 28(35):5219–5228
Kim ES, Herbst RS, Wistuba II et al (2011) The battle trial: personalizing therapy for lung cancer. Cancer Discov 1(1):44–53
Lynch TJ, Bell DW, Sordella R et al (2004) Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 350(21):2129–2139
Tran B, Dancey JE, Kamel-Reid S et al (2012) Cancer genomics: technology, discovery, and translation. J Clin Oncol 30(6):647–660
Vakiani E, Janakiraman M, Shen R et al (2012) Comparative genomic analysis of primary versus metastatic colorectal carcinomas. J Clin Oncol 30(24):2956–2962
Tie J, Gibbs P, Lipton L et al (2011) Optimizing targeted therapeutic development: analysis of a colorectal cancer patient population with the BRAF (V600E) mutation. Int J Cancer 128(9):2075–2084
Diaz Z (2012) Quebec clinical research organization in cancer consortium. Feasibility and challenges of a biopsy-driven and biomarker discovery clinical trial in metastatic colorectal cancer to identify signatures of clinical resistance. ASCO Meeting Abstracts; 30 (15_suppl), e14108
Roychowdhury S, Iyer MK, Robinson DR, et al. (2011) Personalized oncology through integrative high-throughput sequencing: a pilot study. Sci Transl Med 3(111) 111ra21
Thomas RK, Baker AC, Debiasi RM et al (2007) High-throughput oncogene mutation profiling in human cancer. Nat Genet 39(3):347–351
MacConaill LE, Campbell CD, Kehoe SM et al (2009) Profiling critical cancer gene mutations in clinical tumor samples. PLoS ONE 4(11):e7887
Dias-Santagata D, Akhavanfard S, David SS et al (2010) Rapid targeted mutational analysis of human tumours: a clinical platform to guide personalized cancer medicine. EMBO Mol Med 2(5):146–158
Corless CL (2011) Medicine Personalized cancer diagnostics. Science 334(6060):1217–1218
Garraway LA (2012) Concordance and discordance in tumor genomic profiling. J Clin Oncol 30(24):2937–2939
Cawthorn TR, Amir E, Broom R et al (2009) Mechanisms and pathways of bone metastasis: challenges and pitfalls of performing molecular research on patient samples. Clin Exp Metastasis 26(8):935–943
Hilton JF, Amir E, Hopkins S et al (2011) Acquisition of metastatic tissue from patients with bone metastases from breast cancer. Breast Cancer Res Treat 129(3):761–765
Amir E, Clemons M, Purdie CA et al (2012) Tissue confirmation of disease recurrence in breast cancer patients: pooled analysis of multi-centre, multi-disciplinary prospective studies. Cancer Treat Rev 38(6):708–714
Amir E, Miller N, Geddie W et al (2012) Prospective study evaluating the impact of tissue confirmation of metastatic disease in patients with breast cancer. J Clin Oncol 30(6):587–592
Hudson TJ, Anderson W, Artez A et al (2010) International network of cancer genome projects. Nature 464(7291):993–998
Blow N (2009) Biobanking: freezer burn. Nat Methods 6(2):173–178
Hewitt RE (2011) Biobanking: the foundation of personalized medicine. Curr Opin Oncol 23(1):112–119
Alers JC, Krijtenburg PJ, Vissers KJ et al (1999) Effect of bone decalcification procedures on DNA in situ hybridization and comparative genomic hybridization. EDTA is highly preferable to a routinely used acid decalcifier. J Histochem Cytochem 47(5):703–710
Xu C, Houck JR, Fan W et al (2008) Simultaneous isolation of DNA and RNA from the same cell population obtained by laser capture microdissection for genome and transcriptome profiling. J Mol Diagn 10(2):129–134
Van Loo P, Nordgard SH, Lingjaerde OC et al (2010) Allele-specific copy number analysis of tumors. Proc Natl Acad Sci USA 107(39):16910–16915
Nik-Zainal S, Van Loo P, Wedge DC et al (2012) The life history of 21 breast cancers. Cell 149(5):994–1007
Taylor BS, Schultz N, Hieronymus H et al (2010) Integrative genomic profiling of human prostate cancer. Cancer Cell 18(1):11–22
Liu W, Laitinen S, Khan S et al (2009) Copy number analysis indicates monoclonal origin of lethal metastatic prostate cancer. Nat Med 15(5):559–565
Wu JS, Goldsmith JD, Horwich PJ et al (2008) Bone and soft-tissue lesions: what factors affect diagnostic yield of image-guided core-needle biopsy? Radiology 248(3):962–970
Rimondi E, Rossi G, Bartalena T et al (2011) Percutaneous CT-guided biopsy of the musculoskeletal system: results of 2027 cases. Eur J Radiol 77(1):34–42
Amir E, Ooi WS, Simmons C et al (2008) Discordance between receptor status in primary and metastatic breast cancer: an exploratory study of bone and bone marrow biopsies. Clin Oncol (R Coll Radiol) 20(10):763–768
Yau C, Holmes CC (2008) CNV discovery using SNP genotyping arrays. Cytogenet Genome Res 123(1–4):307–312
Li A, Liu Z, Lezon-Geyda K et al (2011) GPHMM: an integrated hidden Markov model for identification of copy number alteration and loss of heterozygosity in complex tumor samples using whole genome SNP arrays. Nucleic Acids Res 39(12):4928–4941
Wineinger NE, Kennedy RE, Erickson SW et al (2008) Statistical issues in the analysis of DNA copy number variations. Int J Comput Biol Drug Des 1(4):368–395
Stoecklein NH, Klein CA (2010) Genetic disparity between primary tumours, disseminated tumour cells, and manifest metastasis. Int J Cancer 126(3):589–598
Dhir R (2008) Prostate cancer biobanking. Curr Opin Urol 18(3):309–314
Simmons C, Miller N, Geddie W et al (2009) Does confirmatory tumor biopsy alter the management of breast cancer patients with distant metastases? Ann Oncol 20(9):1499–1504
Acknowledgments
MKHH has been supported by scholarships from the Royal Australasian College of Surgeons, the National Health and Medical Research Council, Australia, and the Melville Hughes Scholarship, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne. GM is supported by NICTA. NICTA is funded by the Australian Government as represented by the Department of Broadband, Communications and the Digital Economy and the Australian Research Council through the ICT Centre of Excellence program. MK is supported by the Carlo Vaccari Scholarship. We gratefully acknowledge the Australian Genome Research Facility for providing genomics services, Associate Professor Kate Drummond for her assistance in procurement of some samples, and also the men who so kindly donated their metastatic tissues.
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Hong, M.K.H., Sapre, N., Phal, P.M. et al. Percutaneous image-guided biopsy of prostate cancer metastases yields samples suitable for genomics and personalised oncology. Clin Exp Metastasis 31, 159–167 (2014). https://doi.org/10.1007/s10585-013-9617-2
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DOI: https://doi.org/10.1007/s10585-013-9617-2