New instrument improves detection of low-frequency variants and enables personalized treatment options for cancer patients
At Clinical Genomics Uppsala a new instrument with great multiplexing capabilities for ultrasensitive detection, a QX600 Droplet Digital PCR system, has recently been set up. Ultrasensitive detection of genetic variants has emerged as an important area in precision medicine.
Lotte Moens. Photo: David Naylor
While next generation sequencing (NGS) is used extensively in research and healthcare to identify genetic aberrations, many clinical applications require a more sensitive and rapid approach. Accurate identification of genetic aberrations present in small populations of cancer cells not able to be detected by NGS methods is crucial for the monitoring of cancer patients during treatment and follow-up. Droplet digital PCR (ddPCR) is a method for ultrasensitive detection of genetic variants, which can theoretically detect target molecules present at a frequency of less than 0.1% as compared to almost ~1% with NGS.
"ddPCR has emerged as a powerful tool for rapid screening of patients for mutations but also for monitoring cancer patients during treatment, e.g. identification of acquired resistance mutations, detection of minimal residual disease (MRD) or early detection of recurrence. The method provides absolute quantification of target molecules and a simple workflow, allowing for exact and fast laboratory tests. We look forward to starting several new projects with clinical collaborative partners during the coming years”, says Lotte Moens, clinical molecular biologist in pathology and leader of the work package focusing on solid tumors at Clinical Genomics Uppsala.
Malin Melin. Photo: David Naylor
Early detection of small clones that have developed resistance against targeted drugs is of high importance in both leukemias and solid tumors. One example is resistance mutations in the ESR1 gene in metastatic breast cancer. With the new instrument, seven key resistance mutations can be detected in one single well with results in the same day. Due to the high sensitivity this application is also suitable for liquid biopsies (ctDNA). This is a pilot project on the QX600 and will be tested and validated in a collaboration between Clinical Genomics Uppsala and the division Clinical Pathology at Uppsala University Hospital.
“Ultrasensitive detection of genetic variants is of critical importance in precision medicine and one of our strategic focus areas. There are currently many research studies ongoing to evaluate the potential and feasibility of ddPCR for improving cancer diagnostics. We see a clear need for multiplex ddPCR capacity and the new QX600 system will significantly improve the possibilities for the clinical research community in Uppsala and Sweden. This is to our knowledge the first QX600 system available to researchers in Sweden”, says Malin Melin, head of Clinical Genomics Uppsala.
Clinical Genomics Uppsala
Clinical Genomics Uppsala (CGU), SciLifeLab, is a collaboration between Uppsala University and Uppsala University Hospital that was established to accelerate the use of novel genomic methods in diagnostics. The unit has so far implemented >100 tests into clinical routine diagnostics. CGU was established in 2014 and offers services for clinical and translational research as well as identifies, develops and implements new methods for molecular analysis in clinical practice. CGU has a specific focus on development of new clinical applications based on ultrasensitive variant detection, liquid biopsies and long-read sequencing.