Image-based computational quantification and visualization of genetic alterations and tumour heterogeneity

Publication

Image-based computational quantification and visualization of genetic alterations and tumour heterogeneity

Journal Paper/Review - Apr 7, 2016

Zhong Qing, Poyet Cédric, Blattner Miriam, Soldini Davide, Moch Holger, Rubin Mark A, Noske Aurelia, Rüschoff Josef, Haffner Michael C, Jochum Wolfram, Perner Sven, Buhmann Joachim M, Rüschoff Jan H, Guo Tiannan, Gabrani Maria, Schüffler Peter J, Rechsteiner Markus, Liu Yansheng, Fuchs Thomas J, Rupp Niels J, Fankhauser Christian, Wild Peter J

Citation

Zhong Q, Poyet C, Blattner M, Soldini D, Moch H, Rubin M, Noske A, Rüschoff J, Haffner M, Jochum W, Perner S, Buhmann J, Rüschoff J, Guo T, Gabrani M, Schüffler P, Rechsteiner M, Liu Y, Fuchs T, Rupp N, Fankhauser C, Wild P. Image-based computational quantification and visualization of genetic alterations and tumour heterogeneity. Sci Rep 2016; 6:24146.

Type

Journal Paper/Review (English)

Journal

Sci Rep 2016; 6

Publication Date

Apr 7, 2016

Issn Electronic

2045-2322

Pages

24146

Brief description/objective

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.