METHODS OF DETECTING SOMATIC AND GERMLINE VARIANTS IN IMPURE TUMORS

摘要

A system is provided that considers allele fraction shifts as a function of copy number and clonal heterogeneity. The system leverages differences between allele frequencies to differentiate between somatic and normal variants in impure tumor samples. In solid tumors, stromal cells and infiltrating lymphocytes are typically interspersed among the tumor cells. The normal cell contamination in tumors can be leveraged to differentiate somatic from germline variants. We explicitly model allelic copy number and clonal sample fractions so that we can examine how these factors impact the power to detect somatic variants. The system models the copy number alterations, which can also affect the allele frequencies of both somatic and germline variants. The expected allele frequencies can be calculated. The expected allele frequencies for somatic and germline differ with tumor content for different copy number alterations.