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Chunk #15 — Results — Identification of somatic mutations in cancer samples

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Detection of low prevalence somatic mutations in solid tumors with ultra-deep targeted sequencing.
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In the colon primary sample, UDT-Seq identified ten somatic mutations (Figure 2, Table 1; Table S8 in Additional file 2) of which eight are shared with the xenograft sample and two are present only in the tumor. Seven of these mutations are possibly heterozygous in a majority of the cells (prevalence between 31% and 47%) and three have an intermediate prevalence (10% to 23%). This distribution suggests the presence of different cell populations. Of note, KRAS-G12D has a high prevalence (35%); this cancer driver mutation is present in 40% of colorectal cancers and is associated with anti-EGFR therapy resistance [16]. Interestingly, two common APC inactivating mutations (APC-R405X and APC-R283X), both frequent mutations in colorectal cancer, are present at different prevalence (25% and 49%, respectively), suggesting that they occur in different cell populations. Examination of the primary specific mutations (BRAF-intron and KIT-R49C) shows that neither of them has evidence of presence in the xenograft (Figure 2). In the matching colon xenograft sample, we identified 11 somatic mutations, of which 8 are shared with the primary (Figure 2, Table 1). Examination of