Table 1.
Somatic mutations identified in pancreatic juice by digital NGS*
| KRAS | GNAS | RNF43 | TP53 | SMAD4 | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Case# | M/F | Age | Disease group |
Risk** | dNGS# | SNV | dNGS# | SNV | dNGS# | SNV | dNGS# | SNV | dNGS# | SNV |
| #01 | F | 27 | Control | na | 0 | 0 | 0 | 0 | 0 | |||||
| #02 | F | 79 | Control | na | 1 | p.G12D | 0 | 0 | 0 | 0 | ||||
| #03 | F | 77 | Control | na | 0 | 0 | 0 | 0 | 0 | |||||
| #04 | M | 50 | Control | na | 1 | p.G12D | 0 | 0 | 0 | 0 | ||||
| #05 | F | 78 | Control | na | 0 | 0 | 0 | 0 | 0 | |||||
| #06 | M | 76 | Control | na | 0 | 0 | 0 | 0 | 0 | |||||
| #07 | F | 49 | Control | na | 1,2,2 | p.G12D/V, G13D |
0 | 0 | 0 | 0 | ||||
| #08 | F | 65 | Control | na | 0 | 3 | p.R201C | 3 | p.Q402R | 0 | 0 | |||
| #09 | M | 45 | Control | na | 1,2 | p.G12D/V | 0 | 0 | 0 | 0 | ||||
| #10 | F | 68 | Control | na | 0 | 0 | 0 | 0 | 0 | |||||
| #11 | F | 48 | Control | na | 0 | 0 | 0 | 0 | 0 | |||||
| #12 | F | 43 | Control | na | 0 | 0 | 0 | 0 | 0 | |||||
| #13 | F | 44 | Control | na | 0 | 0 | 0 | 0 | 0 | |||||
| #54 | M | 46 | Control | na | 0 | 0 | 0 | 0 | 0 | |||||
| #55 | F | 72 | Control | na | 2 | p.Q61L | 0 | 0 | 0 | 0 | ||||
| #56 | M | 34 | Control | na | 1 | p.Q61L | 0 | 0 | 0 | 0 | ||||
| #57 | F | 52 | Control | na | 1 | p.G12S | 1 | p.R201H | 0 | 0 | 0 | |||
| #58 | M | 66 | Control | na | 0 | 2,2 | p.R201C/H | 0 | 0 | 0 | ||||
| #59 | F | 59 | Control | na | 1 | p.G12S | 0 | 0 | 0 | 0 | ||||
| #60 | M | 59 | Control | na | 1,1 | p.G12D/S | 0 | 0 | 0 | 0 | ||||
| #61 | F | 73 | Control | na | 0 | 0 | 0 | 0 | 0 | |||||
| #62 | M | 48 | Control | na | 0 | 0 | 0 | 0 | 0 | |||||
| #63 | M | 40 | Control | na | 0 | 1 | p.R201C | 0 | 0 | 0 | ||||
| #64 | F | 32 | Control | na | 1 | p.G12D | 0 | 0 | 0 | 0 | ||||
| #15 | M | 64 | IPMNs | f | 1 | p.G12V | 0 | 0 | 0 | 0 | ||||
| #23 | F | 64 | IPMNs | s | 3,4 | p.G12D/V | 0 | 0 | 0 | 0 | ||||
| #24 | M | 21 | IPMNs | s | 3 | p.G13D | 29 | p.R201C | 10,3 | p.R343H, Y550C |
0 | 0 | ||
| #25 | M | 67 | IPMNs | s | 0 | 0 | 0 | 0 | 0 | |||||
| #26 | M | 51 | IPMNs | f | 0 | 4,1 | p.R201C/H | 4,3 | p.P634S, Q402X |
3 | p.R196L | 0 | ||
| #27 | M | 62 | IPMNs | f | 0 | 0 | 0 | 2 | p.R248Q | 0 | ||||
| #28 | M | 70 | IPMNs | s | 1 | p.G12D | 4,1 | p.R201C/H | 0 | 4 | p.K291R | 0 | ||
| #29 | F | 75 | IPMNs | s | 1 | p.G12V | 2 | p.Q227R | 0 | 0 | 0 | |||
| #30 | F | 63 | IPMNs | s | 1,2,4 | p.G12D/V/ R |
0 | 3 | p.S446F | 0 | 0 | |||
| #65 | F | 58 | IPMN | s | 1,1,1 | p.G12D/V, Q61L |
1 | p.Q227R | 0 | 0 | 0 | |||
| #66 | M | 67 | IPMN | s | 9 | p.G12C | 0 | 0 | 0 | 0 | ||||
| #67 | M | 70 | IPMN | s | 1,1 | p.G12D/V | 2 | p.R201C | 0 | 0 | 0 | |||
| #68 | M | 59 | IPMN | s | 1 | p.G12V | 0 | 3 | p.S464G | 0 | 0 | |||
| #69 | F | 65 | IPMN | s | 1,1 | p.G12S, Q61R |
1 | p.R201C | 3 | p.S478P | 0 | 0 | ||
| #70 | M | 62 | IPMN | s | 1 | p.Q61R | 0 | 0 | 3 | p.M246V | 0 | |||
| #71 | F | 84 | IPMN | s | 0 | 0 | 0 | 0 | 0 | |||||
| #72 | M | 66 | IPMN | s | 1,2 | p.G12V, Q61H |
1 | p.R201H | 0 | 0 | 0 | |||
| #73 | F | 60 | IPMN | s | 1 | p.Q61L | 0 | 0 | 0 | 0 | ||||
| #74 | F | 66 | IPMN | s | 1,1,1 | p.G13D, Q61H/R |
0 | 0 | 0 | 0 | ||||
| #75 | M | 70 | IPMN | s | 0 | 0 | 0 | 0 | 0 | |||||
| #76 | M | 41 | IPMN | s | 1,1 | p.G12V, Q61R |
0 | 0 | 2 | p.R175H | 0 | |||
| #77 | F | 55 | IPMN | s | 1 | p.Q61R | 0 | 0 | 0 | 0 | ||||
| #78 | F | 74 | IPMN | s | 1,1,1 | p.G12C, G13D, Q61R |
0 | 3 | p.A148V | 3 | p.R175H | 0 | ||
| #79 | M | 76 | IPMN | s | 0 | 1 | p.Q227R | 5 | p.A629T | 0 | 0 | |||
| #80 | F | 64 | IPMN | s | 1,8 | p.G12V, Q61H |
8 | p.R201C | 0 | 0 | 0 | |||
| #81 | F | 44 | IPMN | s | 2,1,1,1,1 | p.G12D/V/ R, p. Q61H/R |
1 | p.R201H | 0 | 0 | 0 | |||
| #82 | F | 77 | IPMN | s | 1 | p.Q61H | 1 | p.R201H | 0 | 0 | 0 | |||
| #83 | F | 67 | IPMN | s | 2,1,1,2,1 | p.G12D/V/ R/S, G13D |
0 | 0 | 0 | 0 | ||||
| #84 | M | 84 | IPMN | s | 1,1 | p.G12C/S | 1 | p.R201H | 3 | p.G263E | 0 | 0 | ||
| #85 | M | 49 | IPMN | s | 1,2 | p.G12D/V | 0 | 0 | 0 | 0 | ||||
| #86 | F | 74 | IPMN | s | 1,1,1 | p.G12D, Q61H/R |
1 | p.R201C | 3 | p.L122P | 3 | p.Q165X | 0 | |
| #87 | F | 77 | IPMN | s | 1,2,1,1 | p.G12D/V/ S, Q61L |
0 | 0 | 0 | 0 | ||||
| #88 | F | 83 | IPMN | s | 2 | p.G12V | 1 | p.R201H | 0 | 2 | p.R282W | 0 | ||
| #89 | F | 83 | IPMN | s | 0 | 1 | p.R201H | 0 | 4 | p.R248W | 0 | |||
| #90 | M | 70 | IPMN | s | 1,1 | p.G12D, Q61H |
1 | p.Q227P | 0 | 2 | p.G245S | 0 | ||
| #91 | F | 62 | IPMN | s | 1,1,2 | p.G12V/R/ S |
3 | p.R201C | 0 | 0 | 0 | |||
| #92 | F | 70 | IPMN | s | 5,4,2 | p.G12D/V/ C |
3,1 | p.R201C, Q227R |
0 | 0 | 0 | |||
| #93 | M | 62 | IPMN | s | 1,1,1 | p.G12C/S, Q61H |
0 | 0 | 0 | 0 | ||||
| #94 | F | 66 | IPMN | s | 0 | 0 | 0 | 0 | 0 | |||||
| #95 | M | 64 | IPMN | s | 0 | 2 | p.R201C | 0 | 0 | 0 | ||||
| #96 | M | 76 | IPMN | s | 0 | 0 | 0 | 2 | p.R248W | 0 | ||||
| #97 | F | 83 | IPMN | s | 13 | p.G12V | 1,1 | p.R201C/H | 0 | 0 | 0 | |||
| #98 | F | 68 | IPMN | s | 0 | 0 | 0 | 2 | p.Q136X | 0 | ||||
| #99 | F | 60 | IPMN | s | 1,1 | p.Q61L/R | 1 | p.R201H | 3 | p.S111G | 0 | 0 | ||
| #14 | M | 48 | LG-IPMN | s | 0 | 1 | p.R201H | 4 | p.A618V | 0 | 0 | |||
| #16 | F | 63 | LG-IPMN | f | 2 | p.G12D | 0 | 0 | 0 | 0 | ||||
| #17 | F | 60 | LG-IPMN | f | 5,8,1,3,2 | p.G13D, G12C/R/V, Q61R |
8 | p.R201H | 15 | p.L12Rfs | 2 | p.R248Q | 0 | |
| #18 | M | 75 | LG-IPMN | f | 1 | p.G12V | 2,1 | p.Q227R, R201C |
0 | 0 | 0 | |||
| #100 | M | 78 | LG-IPMN | f | 1,2 | p.G13D, Q61R |
1 | p.Q227R | 0 | 2 | p.R175H | 0 | ||
| #101 | M | 72 | LG-IPMN | f | 0 | 0 | 0 | 0 | 0 | |||||
| #19 | F | 67 | IM-IPMN | s | 2 | p.G13D | 2 | p.R201C | 0 | 0 | 0 | |||
| #20 | F | 73 | IM-IPMN | s | 0 | 2 | p.R201C | 0 | 2 | p.R282W | 0 | |||
| #21 | F | 67 | IM-IPMN | s | 1 | p.G12V | 1 | p.R201C | 0 | 0 | 3 | p.W524R^ | ||
| #22 | M | 65 | IM-IPMN | f | 2 | p.G12V | 0 | 0 | 0 | 0 | ||||
| #102 | M | 72 | IM-IPMN | s | 5 | p.Q61H | 0 | 3 | p.R127Q | 0 | 0 | |||
| #103 | F | 75 | IM-IPMN | f | 7,1,18,1,18 | p.G12A/V/ R, G13D, Q61H |
1 | p.R201C | 0 | 0 | 0 | |||
| #104 | M | 71 | HG-IPMN | f | 1,1,2,1,7,4,1 | p.G12D/R/ S, G13D, p.Q61L/H/ P |
0 | 0 | 0 | 0 | ||||
| #31 | M | 79 | PDAC/ IPMNs |
s | 1 | p.G12V | 0 | 0 | 2 | p.R196X | 0 | |||
| #32 | M | 69 | PDAC/ IPMNs |
s | 1 | p.Q61R | 0 | 0 | 3 | p.R175H | 0 | |||
| #33 | F | 74 | PDAC/ IPMNs |
s | 4,2 | p.G13D, G12R |
1 | p.R201H | 0 | 0 | 0 | |||
| #34 | F | 55 | PDAC/ IPMNs |
s | 23,6,3,2,2,2,2,2 | p.G12D/S/ R/C/V, G13C/D |
0 | 3 | p.R454H | 26 | p.R248Q | 0 | ||
| #35 | M | 65 | PDAC/ IPMNs |
f | 1 | p.G12V | 0 | 0 | 3 | p.R248Q | 0 | |||
| #36 | M | 74 | PDAC/ IPMNs |
f | 21 | p.G12D | 2 | p.R201C | 0 | 0 | 26,4 | p.Q311X Q256X |
||
| #37 | M | 69 | PDAC/ IPMN |
s | 0 | 61 | p.R201C | 0 | 87 | p.L194R | 0 | |||
| #38 | M | 73 | PDAC/ IPMNs |
s | 12 | p.G12D | 1,1 | p.R201C/H | 0 | 0 | 0 | |||
| #105 | M | 68 | PDAC/ IPMNs |
s | 1 | p.G12D | 6 | p.R201C | 3,3 | p.F322S, H295R |
8 | p.C141G | 0 | |
| #106 | M | 44 | PDAC/ IPMNs |
s | 10 | p.Q61R | 0 | 0 | 12 | p.R175H | 3 | p.T273fs | ||
| #107 | M | 59 | PDAC/ IPMN |
s | 8,8 | p.G12D/S | 0 | 10 | p.P470fs | 2 | p.R175H | 0 | ||
| #115 | M | 68 | PDAC/ IPMN |
s | 6,1,1 | p.G12C/S, Q61L |
1 | p.R201H | 0 | 3 | p.R181C | 0 | ||
| #39 | M | 70 | PDAC | f | 0 | 0 | 0 | 0 | 0 | |||||
| #40 | M | 53 | PDAC | s | 0 | 0 | 0 | 6 | p. L130Sfs |
0 | ||||
| #41 | F | 46 | PDAC | s | 3,6 | p.G12D/R | 2 | p.R201H | 4 | p.C471R | 0 | 0 | ||
| #42 | M | 78 | PDAC | s | 6,2 | p.G13D, G12V |
1 | p.R201C | 0 | 0 | 0 | |||
| #43 | F | 59 | PDAC | s | 3,5 | p.G12S/V | 0 | 0 | 2 | p.R248W | 0 | |||
| #44 | F | 77 | PDAC | s | 1 | p.G12D | 2 | p.R201C | 5 | p.H556R | 3 | p.R175H | 7 | p.A457V^ |
| #45 | M | 56 | PDAC | s | 6,2 | p.G12D/V | 0 | 4 | p.R519X | 7 | p.Y220C | 0 | ||
| #46 | M | 58 | PDAC | s | 17 | p.G12D | 0 | 0 | 0 | 0 | ||||
| #47 | F | 75 | PDAC | s | 32,22,4,4 | p.G13D, Q61H, G12D/R |
0 | 0 | 2 | p.R273C | 0 | |||
| #48 | M | 59 | PDAC | f | 0 | 0 | 3,3 | p.L109P, V480A |
3 | p.C277R | 3 | p.M543T^ | ||
| #49 | F | 69 | PDAC | s | 23,2 | p.G12V/S | 2 | p.R201C | 0 | 39 | p.R196X | 0 | ||
| #50 | F | 68 | PDAC | s | 0 | 0 | 0 | 0 | 0 | |||||
| #51 | F | 66 | PDAC | s | 0 | 0 | 0 | 0 | 11 | p.K50Kfs | ||||
| #52 | F | 62 | PDAC | f | 4 | p.G12D | 0 | 0 | 0 | 0 | ||||
| #53 | F | 79 | PDAC | f | 1,1 | p.G12D/R | 0 | 0 | 4,1,1 | p.Y220C, R248W/Q |
0 | |||
| #108 | M | 63 | PDAC | s | 0 | 1 | p.Q227R | 0 | 0 | 0 | ||||
| #109 | M | 71 | PDAC | s | 1 | p.Q61H | 0 | 0 | 0 | 0 | ||||
| #110 | M | 70 | PDAC | f | 0 | 0 | 3 | p.H472R | 2 | p.R248W | 0 | |||
| #111 | M | 62 | PDAC | s | 2,1 | p.G12D, G13D |
0 | 0 | 0 | 0 | ||||
| #112 | F | 71 | PDAC | s | 1 | p.Q61H | 1 | p.R201C | 0 | 2,2 | p.R248W, Y163C |
0 | ||
| #113 | F | 77 | PDAC | s | 11 | p.G12V | 1 | p.R201H | 0 | 2 | p.Y220C | 0 | ||
| #114 | M | 57 | PDAC | s | 0 | 0 | 0 | 0 | 0 | |||||
Case #20 had a BRAF K601K mutation (score 4), Case #26 had a TGFBR2 mutation D317Y (score 4), Case #53 had PIK3CA mutations H1047L/R (score 3, 6), Case#105 had a BRAF F595L mutation (score 4), Case # had a Case #107 had a PIK3CA H1047R mutation (score 3).
*
, Other four genes shown in supplementary table;
**
, s: sporadic; f: familial. dNGS#:digital NGS score (mutation concentration); SNV:single nucleotide variant (i.e. somatic mutation).
^
suspected pathogenic.