A sequencing platform that generates ‘clinical-grade’ data using whole exome sequencing (WES) from small amounts of DNA extracted from tumor clinical samples is reported online this week in Nature Medicine. The approach moves the use of WES a step closer in clinical decision-making important for providing best patient care.
WES has emerged as a transformative technology for biological discovery in recent years; however, its widespread use in the clinic has been hampered by the lack of availability of robust methods for using genetic material from one of the common ways patient-derived tumor tissues are stored, FFPE. This archival method is often used to fix surgical tissue samples and biopsies, but it also results in partial degradation of genetic material. In addition, the impact of WES in the clinical care of individual patients has been challenged by the absence of clinical interpretation algorithms to identify clinically relevant alterations and the necessary framework to enable WES data to be prospectively applied to patients.
Eliezer Van Allen and colleagues apply the new clinical WES platform using very small amounts of DNA prospectively to 16 cancer patients and discover clinically actionable findings in 15 of them. The authors also validate the approach using clinical samples representing a range of purities and ages, yielding results with FFPE tumor tissue samples that are comparable to fresh frozen samples, which normally have intact material. One patient with metastatic lung adenocarcinoma was successfully treated based on the results of the exome sequence; however, further studies in larger cohorts will be necessary to determine whether clinical WES will ultimately change routine clinical practice.