Abstract
Circulating tumor cells (CTCs) hold promise as biomarkers to aid in patient treatment stratification and disease monitoring. Because the number of cells is a critical parameter for exploiting CTCs for predictive biomarker’s detection, we developed a FISH (fluorescent in situ hybridization) method for CTCs enriched on filters (filter-adapted FISH [FA-FISH]) that was optimized for high cell recovery. To increase the feasibility and reliability of the analyses, we combined fluorescent staining and FA-FISH and developed a semi-automated microscopy method for optimal FISH signal identification in filtration-enriched CTCs . Here we present these methods and their use for the detection and characterization of ALK-, ROS1-, RET-rearrangement in CTCs from non-small-cell lung cancer and ERG-rearrangements in CTCs from prostate cancer patients.
Cyril Catelain and Emma Pailler are contributed equally to the manuscript.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Baccelli I, Schneeweiss A, Riethdorf S et al (2013) Identification of a population of blood circulating tumor cells from breast cancer patients that initiates metastasis in a xenograft assay. Nat Biotechnol 31(6):539–544
Bergethon K, Shaw AT, Ou SH et al (2012) ROS1 rearrangements define a unique molecular class of lung cancers. J Clin Oncol 30(8):863–870
Chiarle R, Voena C, Ambrogio C et al (2008) The anaplastic lymphoma kinase in the pathogenesis of cancer. Nat Rev Cancer 8(1):11–23
Davies KD, Doebele RC (2013) Molecular pathways: ROS1 fusion proteins in cancer. Clin Cancer Res 19(15):4040–4045
Farace F, Massard C, Vimond N et al (2011) A direct comparison of CellSearch and ISET for circulating tumour-cell detection in patients with metastatic carcinomas. Br J Cancer 105(6):847–853
Gainor JF, Shaw AT (2013) Novel targets in non-small cell lung cancer: ROS1 and RET fusions. Oncologist 18(7):865–875
Hallberg B, Palmer RH (2016) The role of the ALK receptor in cancer biology. Ann Oncol 27(Suppl 3):iii4–iii15
Heitzer E, Auer M, Gasch C et al (2013) Complex tumor genomes inferred from single circulating tumor cells by array-CGH and next-generation sequencing. Cancer Res 73(10):2965–2975
Jemal A, Bray F, Center MM et al (2011) Global cancer statistics. CA Cancer J Clin 61(2):69–90
Ju YS, Lee WC, Shin JY et al (2012) A transforming KIF5B and RET gene fusion in lung adenocarcinoma revealed from whole-genome and transcriptome sequencing. Genome Res 22(3):436–445
Kantoff PW, Higano CS, Shore ND et al (2010) Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 363(5):411–422
Kerr KM, Lopez-Rios F (2016) Precision medicine in NSCLC and pathology: how does ALK fit in the pathway? Ann Oncol 27(Suppl 3):iii16–iii24
Kohno T, Ichikawa H, Totoki Y et al (2012) KIF5B-RET fusions in lung adenocarcinoma. Nat Med 18(3):375–377
Lipson D, Capelletti M, Yelensky R et al (2012) Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies. Nat Med 18(3):382–384
Massard C, Oulhen M, Le Moulec S et al (2016) Phenotypic and genetic heterogeneity of tumor tissue and circulating tumor cells in patients with metastatic castrationresistant prostate cancer: a report from the PETRUS prospective study. Oncotarget 7(34):55069–55082
Oxnard GR, Binder A, Janne PA (2013) New targetable oncogenes in non-small-cell lung cancer. J Clin Oncol 31(8):1097–1104
Pailler E, Adam J, Barthelemy A et al (2013) Detection of circulating tumor cells harboring a unique ALK rearrangement in ALK-positive non-small-cell lung cancer. J Clin Oncol 31(18):2273–2281
Pailler E, Auger N, Lindsay CR et al (2015) High level of chromosomal instability in circulating tumor cells of ROS1-rearranged non-small-cell lung cancer. Ann Oncol 26(7):1408–1415
Pailler E, Oulhen M, Billiot F et al (2016) Method for semi-automated microscopy of filtration-enriched circulating tumor cells. BMC Cancer 16:477
Pao W, Girard N (2011) New driver mutations in non-small-cell lung cancer. Lancet Oncol 12(2):175–180
Rikova K, Guo A, Zeng Q et al (2007) Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell 131(6):1190–1203
Ryan CJ, Smith MR, de Bono JS et al (2013) Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med 368(2):138–148
Scher HI, Fizazi K, Saad F et al (2012) Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med 367(13):1187–1197
Sequist LV, Bell DW, Lynch TJ et al (2007) Molecular predictors of response to epidermal growth factor receptor antagonists in non-small-cell lung cancer. J Clin Oncol 25(5):587–595
Shames DS, Wistuba II (2014) The evolving genomic classification of lung cancer. J Pathol 232(2):121–133
Shaw AT, Kim DW, Nakagawa K et al (2013) Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med 368(25):2385–2394
Soda M, Choi YL, Enomoto M et al (2007) Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 448(7153):561–566
Solomon B, Soria JC (2016) The continuum of care for ALK-positive NSCLC: from diagnosis to new treatment options – an overview. Ann Oncol 27(Suppl 3):iii1–iii3
Takeuchi K, Soda M, Togashi Y et al (2012) RET, ROS1 and ALK fusions in lung cancer. Nat Med 18(3):378–381
Tannock IF, de Wit R, Berry WR et al (2004) Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 351(15):1502–1512
Competing Interests
The authors declare that they have no competing interests.
Funding
CC is supported by the Agence Nationale pour la Recherche (ANR-CE17-0006-01). EP is supported by the LabEx LERMIT (grant no ANR-10-LABX-0033-LERMIT) and the Fondation pour la Recherche Médicale (grant no FDT20150532072). VF is supported by the Fondation pour la Recherche Médicale (grants no FDT20160435543). The authors are grateful for the research support of the Fondation de France (grant no 201300038317), the Fondation ARC pour la Recherche sur le Cancer (grant no 20131200417), Innovative Medicines Initiative 11th Call CANCER ID (IMI-JU-11-2013, 115749), Institut National du Cancer (PRT-K14-032) and Agence Nationale de la Recherche (ANR-CE17-0006-01).
Author’s Contributions
Manuscript drafted by FF and CC. All authors have read and approved the final version of the manuscript.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2017 Springer International Publishing AG
About this chapter
Cite this chapter
Catelain, C., Pailler, E., Oulhen, M., Faugeroux, V., Pommier, AL., Farace, F. (2017). Detection of Gene Rearrangements in Circulating Tumor Cells: Examples of ALK-, ROS1-, RET-Rearrangements in Non-Small-Cell Lung Cancer and ERG-Rearrangements in Prostate Cancer. In: Magbanua, M., Park, J. (eds) Isolation and Molecular Characterization of Circulating Tumor Cells. Advances in Experimental Medicine and Biology, vol 994. Springer, Cham. https://doi.org/10.1007/978-3-319-55947-6_9
Download citation
DOI: https://doi.org/10.1007/978-3-319-55947-6_9
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-55946-9
Online ISBN: 978-3-319-55947-6
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)