Recent large-scale genome analyses of human tissue samples have uncovered a high degree of genetic alterations and tumour heterogeneity in most tumour entities, independent of morphological phenotypes and histopathological characteristics.
Assessment of genetic copy-number variation (CNV) and tumour heterogeneity by fluorescence in situ hybridization (ISH) provides additional tissue morphology at single-cell resolution, but it is labour intensive with limited throughput and high inter-observer variability. We present an integrative method combining bright-field dual-colour chromogenic and silver ISH assays with an image-based computational workflow (ISHProfiler), for accurate detection of molecular signals, high-throughput evaluation of CNV, expressive visualization of multi-level heterogeneity (cellular, inter- and intra-tumour heterogeneity), and objective quantification of heterogeneous genetic deletions (PTEN) and amplifications (19q12, HER2) in diverse human tumours (prostate, endometrial, ovarian and gastric), using various tissue sizes and different scanners, with unprecedented throughput and reproducibility.
Scientific reports. 2016 Apr 07*** epublish ***
Qing Zhong, Jan H Rüschoff, Tiannan Guo, Maria Gabrani, Peter J Schüffler, Markus Rechsteiner, Yansheng Liu, Thomas J Fuchs, Niels J Rupp, Christian Fankhauser, Joachim M Buhmann, Sven Perner, Cédric Poyet, Miriam Blattner, Davide Soldini, Holger Moch, Mark A Rubin, Aurelia Noske, Josef Rüschoff, Michael C Haffner, Wolfram Jochum, Peter J Wild
Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland., Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland., Institute of Molecular Systems Biology, ETH, Zurich, Switzerland., Zurich Labouratory, IBM Research-Zurich, Rueschlikon, Switzerland., Department of Computer Science, ETH, Zurich, Switzerland., Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland., Institute of Molecular Systems Biology, ETH, Zurich, Switzerland., Memorial Sloan Kettering Cancer Center, New York, NY, USA., Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland., Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland., Institute of Molecular Systems Biology, ETH, Zurich, Switzerland., Department of Prostate Cancer Research, Institute of Pathology, University Hospital of Bonn, Bonn, Germany., Department of Urology, University Hospital Zurich, Zurich, Switzerland., Institute for Precision Medicine and Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University and New York-Presbyterian Hospital, New York, NY, USA., Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland., Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland., Institute for Precision Medicine and Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University and New York-Presbyterian Hospital, New York, NY, USA., Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland., Targos Molecular Pathology, Pathology Nordhessen, Kassel, Germany., Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA., Institute of Pathology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland., Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.