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

Open access
Date
2016-04-07Type
- Journal Article
Citations
Cited 19 times in
Web of Science
Cited 23 times in
Scopus
ETH Bibliography
yes
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Abstract
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. Show more
Permanent link
https://doi.org/10.3929/ethz-b-000115159Publication status
publishedExternal links
Journal / series
Scientific ReportsVolume
Pages / Article No.
Publisher
Nature Publishing GroupSubject
Tumour heterogeneity; Computational modelsOrganisational unit
03659 - Buhmann, Joachim M. / Buhmann, Joachim M.
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Show all metadata
Citations
Cited 19 times in
Web of Science
Cited 23 times in
Scopus
ETH Bibliography
yes
Altmetrics