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Impact of tumor heterogeneity and tissue sampling for genetic mutation testing: a systematic review and post hoc analysis

      Highlights

      • No formal guidelines were found that described sample bias due to tumor heterogeneity.
      • Forty-two percent of tissue sample data sets were not accompanied by pathology results.
      • Fifty-eight percent of tissue sample data sets were not diagnosed directly.
      • Forty-two percent of tissue sample data sets failed to report on tumor purity (reported ranges 10% to 100%)
      • The reporting standards for tumor tissue samples need to be improved.

      Abstract

      Objective

      The objective of the study was to identify guidelines to assist systematic reviewers or clinical researchers in identifying sampling bias due to tumor heterogeneity (TH) in solid cancers assayed for somatic mutations. We also assessed current reporting standards to determine the impact of TH on sample bias.

      Study Design and Setting

      We conducted a systematic review searching 13 databases (to January 2019) to identify guidelines. A post hoc analysis was performed using 12 prostate tumor somatic mutation data sets from a previous systematic review to assess reporting on TH.

      Results

      Searches identified 2,085 records. No formal guidelines were identified. Forty publications contained incidental recommendations across five major themes: using multiple tumor samples (n = 29), sample purity thresholds (n = 14), using specific sequencing methods (n = 8), using liquid biopsies (n = 4), and microdissection (n = 4). In post hoc analyses, 50% (6 of 12) clearly reported pathology methods. Forty-two percent (5 of 12) did not report pathology results. Forty-two percent (5 of 12) confirmed the pathology of the sample by direct diagnosis rather than inference. Forty-two percent (5 of 12) used multiple samples per patient. Fifty-eight percent (7 of 12) reported on tumor purity (reported ranges 10% to 100%).

      Conclusions

      As precision medicine progresses to the clinic, guidelines are required to help evidence-based decision makers understand how TH may impact sample bias. Authors need to clearly report pathology methods and results and tumor purity methods and results.

      Keywords

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