In an accompanying paper, we review the theoretical principles of tumor mutations and the observed patterns of mutations in the cancer literature. These patterns are discussed in the context of a perceived dichotomy in quality that exists among mutation reports. Due to the frequency of mis-reporting, a systematic approach to the somatic mutation literature in human cancer is needed. We propose a multiple-criterion numerical tool, referred to as the scoring SISTM (System for Intragenic Somatic Tumor Mutations), which effectively discriminates promising and unpromising somatic mutation reports in human cancer. Reports are assessed on 12 criteria, and are given a final score of 15 or less. Scores in the range of 10 to 15 are suggestive of well presented reports of disease-inducing somatic mutations. Reports with scores less than 10 should be viewed with skepticism.
In order to demonstrate the relevance and potential of the scoring SISTM, we applied the criteria to 27 novel and 31 confirmatory (i.e., non-novel) mutation reports. The median score of the 58 reports was 10, suggesting that roughly half of the mutation reports were problematic. Reports convincingly validated by an independent study had higher scores than reports that were never validated (p<0.001). In a related analysis of quality in the mutation literature, reports that used relatively pure tissue with high DNA concentrations (i.e. cell lines or xenografts) were validated more frequently (odds ratio 4, p=0.03) by an independent study than reports that used tissue having mixed cellular components and low DNA concentrations (e.g. primary tumor).
We conclude that problematic reports of somatic mutations in human cancer are common and propose the scoring SISTM as a useful adjunct to interpret mutation reports. Tissue type is an important variable in mutation studies and has been a predictor for study validation in the somatic mutation literature.Full Text Options