As whole-genome sequencing is poised to play a larger role in clinical cancer care, a critical decision point is nearing for addressing how cancer specimens are handled, argue the authors of a viewpoint piece published Jan. 2 in the Journal of the American Medical Association. Standards must be established for acquiring appropriate tissue samples that […]
As whole-genome sequencing is poised to play a larger role in clinical cancer care, a critical decision point is nearing for addressing how cancer specimens are handled, argue the authors of a viewpoint piece published Jan. 2 in the Journal of the American Medical Association. Standards must be established for acquiring appropriate tissue samples that can be used in routine pathologic practice to inform treatment decision in cancer genomic medicine, they say.“Deciding how best to obtain these samples and how best to process them for whole genome or exome sequencing is a pivotal yet unresolved issue with several layers of complexity,” writes co-author Eric Topol, M.D., from Scripps Translational Science Institute in La Jolla, Calif. “Pathologists currently optimize tumor sampling and processing to leverage standard diagnostic methods. However, as the new clinical applicability of genomics emerges at a fairly rapid rate, the field of pathology will arrive at the tipping point for a fundamental change in how cancer specimens are handled.” The increased affordability of sequencing technology, coupled with the growing understanding of the heterogeneous nature of the genetic complexity of solid tumors, is causing some to question the ultimate utility of the current standard of formalin-fixed specimens in favor of frozen tissues required for whole-genome and -exome sequencing. “Research studies using freshly frozen tumor tissue suggest an expanded capability of a ‘panor-omic’ assessment, which includes whole genome sequencing, RNA sequencing, and epigenomic profiling to detect methylation and histone modifications,” write the authors. This shift in specimen preference, however, poses a clinical dilemma. Medicine is evolving toward less invasive procedures like needle biopsies and aspirations, which yield smaller tissue samples. The migration toward comprehensive genomic analysis may require an extra step of sample preparation and extra tissue accordingly. The proof that larger biopsies reveal additional actionable mutations and, hence, better clinical outcomes is missing. “Moving the pathology and oncology communities toward a new practice incorporating larger tissue samples and the routine use of frozen tissue represents a formidable but attainable change, one that will undoubtedly involve patients’ preferences and consent,” the authors conclude. “How quickly a new practice should emerge depends on clinical studies indicating improved patient outcomes associated with detailed genetic evaluation.” The authors note that ongoing research exploring whether free circulating plasma DNA is more representative for identifying driver mutations than the sample selected from solid tissue may reverse the need for larger tissue samples while still providing the ability to provide comprehensive genomic analysis using increasingly noninvasive means.
This content is exclusive to Diagnostic Testing and Emerging Technologies subscribers
Start a Free Trial for immediate access to this article and our entire archive of over 20 years of DTET reports.