Interior mutations in 295 FL-L1Hs source elements in the patient's genome. (A) The total number of mutations in each FL-L1Hs source element is depicted, grouped by pre-Ta and Ta subfamilies (Boissinot et al. 2000). (B) The Chr 17 FL-L1Hs source element profile is compared to the three closest FL-L1Hs elements in the patient's genome. Although the three most similar elements have 15, 14, and 14 mutations in common with the Chr 17 source element, respectively (middle of Venn diagram), they have 18 total differences (Δ) in all three examples. Similar results were obtained with the remaining elements in the patient's genome (Supplemental Table S2). (C) Mutation frequencies in FL-L1Hs source elements. Individual mutations are plotted by the total number of FL-L1Hs elements in which they are found. A total of 2788 mutations are confined to a single source element (leftmost bar), whereas only a few mutations are shared by the majority of the 295 FL-L1Hs elements in the patient's genome (right bars). This large collection of singleton mutations, and the profiles that are generated by combining these mutations, has allowed us to identify source elements that generated specific somatic offspring insertions in the tumor (Fig. 3) and also allowed us to evaluate the expression of these elements (Fig. 4). (D–F) Mutation profiles for the Chr 17 (D), Chr 14 (E), and Chr 12 (F) source elements. All three of these source elements are heterozygous in our patient's genome. Differences from the reference L1.3 element (GenBank ID L19088) (Dombroski et al. 1993) are marked in green, red, blue, and yellow and represent mutations to A, T, C, or G, respectively. We also determined the “allele frequencies” at which mutations appear in the FL-L1Hs source elements from the patient's genome and have depicted these in pie charts above each mutation. Mutations that uniquely tag a single element are marked with a star (*). Black bars above the 3′ ends depict the signatures of mutations that were used to identify somatic offspring insertions in the tumor.
