TY - JOUR AU - Cmero, Marek AU - Yuan, Ke AU - Ong, Cheng Soon AU - Schröder, Jan AU - PCAWG, Evolution AU - Heterogeneity Working, Group AU - Corcoran, Niall M AU - Papenfuss, Tony AU - Hovens, Christopher M AU - Markowetz, Florian AU - Macintyre, Geoff AU - PCAWGConsortium TI - Inferring structural variant cancer cell fraction. JO - Nature Communications VL - 11 IS - 1 SN - 2041-1723 CY - [London] PB - Nature Publishing Group UK M1 - DKFZ-2022-01626 SP - 730 PY - 2020 N1 - siehe Correction: DKFZ Autoren affiliiert im PCAWG Consortium:https://inrepo02.dkfz.de/record/212436 / https://doi.org/10.1038/s41467-022-32338-5 AB - We present SVclone, a computational method for inferring the cancer cell fraction of structural variant (SV) breakpoints from whole-genome sequencing data. SVclone accurately determines the variant allele frequencies of both SV breakends, then simultaneously estimates the cancer cell fraction and SV copy number. We assess performance using in silico mixtures of real samples, at known proportions, created from two clonal metastases from the same patient. We find that SVclone's performance is comparable to single-nucleotide variant-based methods, despite having an order of magnitude fewer data points. As part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) consortium, which aggregated whole-genome sequencing data from 2658 cancers across 38 tumour types, we use SVclone to reveal a subset of liver, ovarian and pancreatic cancers with subclonally enriched copy-number neutral rearrangements that show decreased overall survival. SVclone enables improved characterisation of SV intra-tumour heterogeneity. KW - Algorithms KW - Computational Biology: methods KW - Computer Simulation KW - DNA Copy Number Variations KW - Female KW - Gene Frequency KW - Genome, Human KW - Humans KW - Liver Neoplasms: genetics KW - Liver Neoplasms: pathology KW - Male KW - Neoplasms: genetics KW - Neoplasms: pathology KW - Ovarian Neoplasms: genetics KW - Ovarian Neoplasms: pathology KW - Pancreatic Neoplasms: genetics KW - Pancreatic Neoplasms: pathology KW - Prostatic Neoplasms: genetics KW - Prostatic Neoplasms: pathology KW - Sensitivity and Specificity KW - Whole Genome Sequencing LB - PUB:(DE-HGF)16 C6 - pmid:32024845 C2 - pmc:PMC7002525 DO - DOI:10.1038/s41467-020-14351-8 UR - https://inrepo02.dkfz.de/record/180877 ER -