Table 1. Results of targeted gene sequencing analysis compared to ddPCR analysis on archived tumor samples and plasma samples at baseline (BL) and after 14 days (D14) of regorafenib therapy (cycle 1). Patient RGR-7 was excluded due to a poor quality blood sample at BL and D14. VAF, variant allele frequency.
Patient | Gene | Mutation | Variant | Targeted sequencing | ddPCR | ||||
---|---|---|---|---|---|---|---|---|---|
VAF (%) tumor | VAF (%) plasma baseline | VAF (%) plasma D14 (C1) | VAF (%) tumor | VAF (%) plasma baseline | VAF (%) plasma D14 (C1) | ||||
RGR-1 | APC | p.R213* | c.637C>T2 | 16,83 | 26,13 | 16,55 | 11,4 | 26,2 | 11,84 |
KRAS | p.A146V | c.437C>T2 | 26,84 | 57,47 | 20,72 | 26 | 59,1 | 26,6 | |
TP53 | p.R175H | c.524G>A2 | 34,94 | 67,46 | 28,94 | 33,2 | 71,8 | 33,4 | |
RGR-2 | APC | p.Y1376* | c.4128T>A2 | 35,55 | 2,05 | <1 | 62,4 | 4 | 0 |
KRAS | p.G12V | c.35G>T2 | 18,97 | WT | WT | 29,5 | 1,3 | 0,09 | |
RGR-4 | BRAF | p.V600E | c.1799T>A2 | 19,51 | 21,12 | 9,95 | 21,9 | 23,8 | 14,8 |
KRAS | p.G12D | c.35G>A2 | 7,14 | WT | WT | 7,14 | 0,05 | 0,04 | |
PIK3CA | p.H1047R | c.3140A>G2 | 36,24 | 36,18 | 23,55 | 31,1 | 41,1 | 24,4 | |
RGR-7 | PIK3R1 | p.S102* | c.305C>A2 | 19,08 | 44,53 | 49,27 | 20,6 | 44,8 | - |
TP53 | p.H214R | c.641A>G3 | 24,16 | 42,55 | 30,6 | 18,1 | - | - | |
RGR-14 | KRAS | p.G12D | c.35G>A2 | 36,62 | 24,69 | 10,05 | 36,6 | 31,4 | 18,3 |
RGR-24 | APC | p.S1032* | c.3095C>A2 | 18,73 | 54,17 | 12,58 | 27,6 | 41,7 | 19,1 |
RGR-26 | KRAS | p.G12S | c.34G>A2 | 28,77 | 15,99 | 8,61 | 24,9 | 19,3 | 12,9 |
TP53 | p.R196* | c.586C>T2 | 37,5 | 20,32 | 12,35 | 28,1 | 23,3 | 13,2 | |
RGR-28 | SMAD3 | p.F343L | c.1029C>A | 21,19 | 5,72 | <1 | 17,7 | 7 | 0,98 |
TP53 | p.R273H | c.818G>A3 | 34,5 | 5,36 | <1 | 47,5 | 11 | 1,7 | |
RGR-30 | NRAS | p.G12V | c.35G>T2 | 51,04 | 42,93 | 26 | 48,9 | 45,6 | 32,8 |
APC | p.W685* | c.2054G>A2 | 42,01 | 32,34 | 19,63 | 27 | 32 | 18,8 | |
TP53 | p.G245S | c.733G>A | 51,35 | 38,5 | 15,61 | 49,4 | 44 | 23,3 | |
RGR-35 | KRAS | p.G12C | c.34G>T2 | 13,21 | 7,9 | <1 | 12,8 | 7,9 | 1,34 |
PIK3CA | p.E545K | c.1633G>A2 | 12,74 | 9,93 | 1,49 | 15,5 | 8,2 | 1,74 | |
TP53 | p.R248Q | c.743G>A3 | 19,51 | 9,27 | 1,13 | 17 | 8,5 | 1,21 | |
RGR-38 | APC | p.E941* | c.2821G>T2 | 21,28 | 5,03 | 1,54 | 22,7 | 8,2 | 2,4 |
KRAS | p.G12D | c.35G>A2 | 19,94 | 2,78 | 1,64 | 23,1 | 8 | 1,9 | |
RGR-43 | NRAS | p.G12D | c.35G>A2 | 26,49 | 4,34 | <1 | 26,8 | 7,1 | 0,27 |
APC | p.R283* | c.847C>T2 | 18,03 | 5,95 | <1 | 31,6 | 7 | 0,15 | |
TP53 | p.R248Q | c.743G>A3 | 37,72 | 7,11 | <1 | 36,9 | 6,9 | 0,29 | |
RGR-44 | KRAS | p.Q61H | c.183A>C2 | WT | 12,54 | 10,4 | WT | 12,8 | 12 |
PIK3CA | p.F83L | c.247TTT>AAA | 31,23 | 36,5 | 30,04 | 33,7 | 41,4 | 38 | |
APC | p.R232* | c.694C>T2 | 12,57 | 1,5 | 1,46 | 14,87 | 1,3 | 1,19 | |
RGR-46 | KRAS | p.G13R | c.37G>C2 | 35,04 | 7,66 | 5 | 30,3 | 11,9 | 6,36 |
PIK3CA | p.E545K | c.1633G>A2 | 39,22 | 13,91 | 8,48 | 34,9 | 14 | 7,42 | |
APC | p.Q1429* | c.4285C>T2 | 34,28 | 10,15 | 5,72 | 29,1 | 14,8 | 6,8 | |
RGR-50 | PIK3CA | p.E542K | c.1624G>A2 | 20,42 | 31,06 | 16,06 | 20,1 | 32 | 16,4 |
KRAS | p.G12V | c.35G>T2 | 22,79 | 54,82 | 29,03 | 22 | 60,8 | 39,1 | |
TP53 | p.R110P | c.329G>C | 24,14 | 39,57 | 19,4 | 28,4 | 43,6 | 19 | |
RGR-51 | KRAS | p.G12A | c.35G>C2 | 35,34 | 25,84 | 16,99 | 32,2 | 29,1 | 19,6 |
APC | p.Q1429* | c.4285C>T2 | 35,43 | 24,32 | 15,41 | 30,7 | 29,8 | 18,87 | |
TP53 | p.G245S | c.733G>A | 47,14 | 36,86 | 21,07 | 49,8 | 43 | 25 | |
RGR-54 | KRAS | p.G13D | c.38G>A2 | 12,36 | <1 | <1 | 17,8 | 0,29 | 0,2 |
PIK3CA | p.G1049R | c.3145G>C | 13,48 | <1 | <1 | 15,4 | 0 | 0,013 | |
APC | p.R232* | c.694C>T2 | 20,13 | <1 | <1 | 19 | 0,06 | 0,1 | |
RGR-56 | TP53 | p.R337C | c.1009C>T | 41,4 | 39,92 | 18,22 | 39,8 | 44,7 | 22,6 |
APC | p.Q1367* | c.4099C>T2 | 27,06 | 19,68 | 7,54 | 31 | 31,1 | 13,4 | |
NOTCH1 | p.A1104T | c.3310G>A | 31,09 | 16,87 | 7,9 | 27,9 | 17,8 | 8,4 | |
RGR-58 | KRAS | p.G12C | c.34G>T2 | 2,86 | 63,42 | 20,94 | 3,6 | 61,4 | 17,6 |
TP53 | p.M237K | c.710T>A2 | 1,47 | 64,11 | 19,59 | 1,16 | 63,4 | 24,9 | |
RGR-61 | APC | p.A1492Cfs*1513 | c.2510_2511insT2 | 30,85 | 19,9 | 20,3 | 35,6 | 24,5 | 22,5 |
KRAS | p.Q61H | c.183A>C2 | 33,36 | 23,27 | 32,9 | 36,3 | 31,8 | 38,4 | |
TP53 | p.R158H | c.473G>A | 63,7 | 27,62 | 29,85 | 67,6 | 35,3 | 38,9 | |
FBXW7 | p.A422Qfs*443 | c.1262delC | 61,42 | 46,72 | 31,5 | 60,9 | 34,3 | 38,5 |