Integrative reconstruction of cancer genome karyotypes using InfoGenomeR.

Annotation of structural variations (SVs) and base-level karyotyping in cancer cells remains challenging. Here, we present Integrative Framework for Genome Reconstruction (InfoGenomeR)-a graph-based framework that can reconstruct individual SVs into karyotypes based on whole-genome sequencing data, by integrating SVs, total copy number alterations, allele-specific copy numbers, and haplotype information. Using whole-genome sequencing data sets of patients with breast cancer, glioblastoma multiforme, and ovarian cancer, we demonstrate the analytical potential of InfoGenomeR. We identify recurrent derivative chromosomes derived from chromosomes 11 and 17 in breast cancer samples, with homogeneously staining regions for CCND1 and ERBB2, and double minutes and breakage-fusion-bridge cycles in glioblastoma multiforme and ovarian cancer samples, respectively. Moreover, we show that InfoGenomeR can discriminate private and shared SVs between primary and metastatic cancer sites that could contribute to tumour evolution. These findings indicate that InfoGenomeR can guide targeted therapies by unravelling cancer-specific SVs on a genome-wide scale.