An algorithm to evaluate the efficacy of detecting somatic mutations

Abstract

Detection of somatic mutations from late stage solid tumors is a critical part of cancer treatment. Although tumor content is used as a convenient parameter to measure efficacy of detection, it fails to include two basic factors: the lower limit of detection (LLOD), and the ratio of the mutant and wild type allele frequencies.  Recently, the detection of somatic mutations has expanded to liquid biopsy, early stages of cancer and population screening, which all generally carry lower copy numbers of somatic mutations compared to late stage tumors.  With the growing importance of these mutations for targeted chemotherapy and other clinical applications, there is a need re-evaluate the efficacy of detection of somatic mutations.  Hence, a new algorithm, Detection Index (DI), is proposed to standardize the efficacy of all molecular methods and is applicable to all types of clinical samples. Detection Index (DI) is based on two basic determinants: lower limit of detection of the mutant allele, and the ratio of the copies of the mutant allele to that of the wild-type. The benefits of DI include (a) standardization of methods detecting somatic mutations so that laboratory reports will have a uniform interpretation related to clinical picture, and (b) the flexibility to use appropriate amounts of DNA and assay conditions to achieve desired DI.