Somatic Mutation Detection from Liquid Biopsies via NGS: Urological Cancers



Next generation sequencing (NGS) of blood-derived nucleic acids is an emerging paradigm for determining the mutational status of cancer patients over time. Both circulating tumor cells (CTC) and cell-free circulating DNA have been proposed as possible sample types for extracting tumor DNA. Here we present data from a CTC enrichment modality that results in tumor cell purities of >10% and a high sensitivity NGS data analysis workflow that enables the use of standard amplicon panels typically used for primary tissue. This study is aimed at urological cancers (kidney, prostate), and adds to previously published data presented for bladder cancer patients using this technique.


Multisite analytical validation data, based on spiking of cells into whole blood, and a matched molecular and bioinformatics approach demonstrate a detection limit down to 10 cells from a blood draw with a false positive rate of below 0.1 calls per sample. Clinical data from two different urological cancer pilot studies (prostate and kidney) demonstrates the detection of somatic variants for a majority of samples, and significant overlap between detected mutations and known somatic mutation sites. For example, in prostate patients, we detect common mutations (i.e. TP53, PTEN and APC genes) that are similar to the population distribution of mutation rates in tissue biopsies.


This assay makes possible the detection of somatic variants from urological cancer patients without the need for a tissue biopsy.