GSE119763 Exploring the spatiotemporal genetic heterogeneity in metastatic lung adenocarcinoma using a nuclei flow-sorting approach

Contributors : Thomas Lorber ; Noemi Andor ; Tanja Dietsche ; Valeria Perrina ; Darius Juskevicius ; Karen Pereira ; Stephanie U Greer ; Arthur Krause ; David Mueller ; Spasenija S Prince ; Didier Lardinois ; Michael T Barrett ; Christian Ruiz ; Lukas BubendorfSeries Type : Genome variation profiling by genome tiling arrayOrganism : Homo sapiensVariable tumor cellularity can limit sensitivity and precision in comparative genomics, because differences in tumor content can result in misclassifying truncal mutations as region-specific private mutations in stroma-rich regions, especially when studying tissue specimens of mediocre tumor cellularity such as LUADs. To address this issue, we refined a nuclei flow-sorting approach by sorting nuclei based on ploidy and the LUAD lineage marker thyroid transcription factor 1 (TTF-1) and applied this method to investigate genome-wide somatic copy number aberrations (SCNA) and mutations of 409 cancer genes in 39 tumor populations obtained from 16 primary tumors and 21 matched metastases. This approach increased the mean tumor purity from 54% (range: 7-89%) of unsorted material to 92% (range: 79-99%) after sorting. Despite this rise in tumor purity, we detected limited genetic heterogeneity between primary tumors and their metastases. In fact, 88% of SCNAs and 80% of mutations were propagated from primary tumors to metastases and low allele frequency mutations accounted for much of the mutational heterogeneity. Even though the pr...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Genome variation profiling by genome tiling array Homo sapiens Source Type: research