The Complexity of Cancer Biospecimens: Understanding a Major Source of Irreproducible Results in Cancer Research

Cancer is a complex disease, the understanding of which is further challenged by the complexity of the biological samples that serve as disease surrogates for molecular study. Acquiring cancer biospecimens for study is, itself, governed by complex medical, ethical and legal issues. The samples, themselves, typically represent only small foci of a much larger and heterogeneous process that makes sampling bias an inescapable challenge. Individual samples may themselves be highly heterogeneous. More importantly, in the process of acquiring them for study, cancer biospecimens are viable and subjected to a myriad of physical, pharmacological, and physiological stresses that alter both the molecular composition and integrity. The iatrogenic contributions to the numerous types and degrees of pre-analytical variation in cancer samples are less well recognized, poorly documented, and largely ignored by the translational research community. This presentation will review the essential sources of both biological and artefactual biospecimen variation that need to be recognized and addressed in translational research.