Genomic analysis in personalized diagnostics

2017 Clinical Chemistry and Laboratory Medicine  
High-quality genomic analyses are essential for precision medicine approaches to cancer patient management. Tumor-specific genomic alterations can be identified in cell-free tumor DNA (ctDNA) from patient blood samples and complement biopsies for real-time molecular treatment monitoring, early recurrence detection, resistance tracking, and identification of candidates for targeted therapies. The US FDA recently approved the first such "liquid biopsy" test for EGFR mutations in patients with
more » ... small cell lung cancer (NSCLC). ctDNA allows for the identification of specific mutations selected by treatment, such as EGFR T790M or C797S in NSCLC patients treated with tyrosine kinase inhibitors. ctDNA can also detect mutations such as KRAS G12V in colorectal cancer and BRAF V600E/V600K in melanoma. Chromosomal aberration pattern analysis by low coverage whole genome sequencing is a new broader approach based on genomic instability. Gains and losses of chromosomal regions detected in plasma ctDNA can be used to compute a genomic copy number instability (CNI) score. The CNI discriminated prostate cancer from both controls and benign prostatic disease. Change in CNI can serve as an early predictor of therapeutic response to chemo/immunotherapy in many cancer types. The CNI score was superior to clinical parameters for prediction of recurrence-free survival in head and neck cancer patients. Molecular biomarkers have attracted special attention in transplantation because of the still unresolved problems that limit long-term outcome. Biomarkers are especially needed that can be used to facilitate personalized immunosuppression. A particularly promising new approach for the early detection of graft rejection is based on the determination of graft-derived circulating cell-free DNA (GcfDNA). Various independent studies have shown that GcfDNA detects rejection episodes early, at an actionable stage, and is a more reliable marker of graft injury, compared to conventional tests. GcfDNA may also be useful to guide changes in immunosuppression and to monitor immunosuppression minimization. In summary, such molecular approaches will allow more personalized treatment that shifts emphasis from reaction to prevention, provides actionable healthcare information, and improves outcomes at lower healthcare costs.
doi:10.1515/cclm-2017-7011 fatcat:ukrbqvtn6jhx7ivyu6mn5a4pjq