Top


Example panel was designed to interrogate Acute myeloid leukemia (AML) tumors. 47 genes were in the input to generate the panel. JAK2 was included as specified by the user. However, JAK2 was not mutated in the panel cohort.

The total number of kilo base pairs included in the panel was set by user to 20.

Example panel (only Tier 1 genes) would contain 0.26 DNA Kbps and include 6 genes/gene fragments; it would identify 50.0% of the 196 tumors in the cohort.

  • AML Cancer Types
    196 Samples available for analysis
  • Tier 1 genes/regions
    number of genes/regions 6
    maximum mutational coverage 50.0%
  • Tier 2 genes/regions
    number of genes/regions 20
    maximum mutational coverage 72.0%

Gene/region Panel tier Bp length gene/region Cumulative mutational coverage Cumulative KBps in panel Relevant mutations AML coverage
NPM1 Ex11(aa:287-288) Tier1 5 0.265 0.005 Resp 0.265
IDH2 Ex4(aa:140-172) Tier1 97 0.347 0.102 Resp 0.102
IDH1 Ex4(aa:132) Tier1 2 0.398 0.104 Resp 0.097
RUNX1 Ex5(aa:141-164) Tier1 71 0.434 0.175 0.041
DNMT3A Ex23(aa:882-909) Tier1 83 0.469 0.258 Resp 0.153
NRAS Ex3(aa:61) Tier1 3 0.5 0.261 Resp Resis 0.031
FLT3 Ex20(aa:835-839) Tier2 14 0.526 0.275 0.087
U2AF1 Ex2(aa:34) Tier2 1 0.546 0.276 0.036
FLT3 Ex14(aa:582-601) Tier2 59 0.566 0.335 0.036
TP53 Ex6(aa:193-223) Tier2 91 0.587 0.426 Resp Resis 0.02
WT1 Ex7(aa:370-402) Tier2 97 0.607 0.523 0.041
KIT Ex17(aa:816) Tier2 2 0.622 0.525 0.026
TP53 Ex8(aa:273-286) Tier2 41 0.638 0.566 Resp Resis 0.015
EZH2 Ex20(aa:744) Tier2 2 0.643 0.568 Resp 0.01
TP53 Ex10(aa:337-342) Tier2 16 0.653 0.584 Resp Resis 0.01
KRAS Tier2 570 0.663 1.154 Resp Resis 0.041
PHF6 Tier2 1098 0.673 2.252 0.026
NRAS Ex2(aa:12-13) Tier2 4 0.679 2.256 Resp Resis 0.041
KIT Ex8(aa:416-418) Tier2 6 0.684 2.262 0.015
RUNX1 Ex6(aa:198-201) Tier2 11 0.689 2.273 0.031
TET2 Ex11(aa:1863-1868) Tier2 15 0.694 2.288 0.01
TP53 Ex5(aa:172-179) Tier2 21 0.699 2.309 Resp Resis 0.015
TET2 Ex7(aa:1307-1316) Tier2 27 0.704 2.336 0.01
PTPN11 Ex3(aa:60-72) Tier2 37 0.709 2.373 0.02
TET2 Ex10(aa:1422-1452) Tier2 91 0.714 2.464 0.02
DNMT3A Ex20(aa:781-792) Tier3 34 0.719 2.498 Resp 0.01
TET2 Ex9(aa:1352-1381) Tier3 88 0.719 2.586 0.015
DNMT3A Ex15(aa:590-615) Tier3 77 0.719 2.663 Resp 0.015
TET2 Ex3(aa:916-947) Tier3 94 0.719 2.757 0.01
TET2 Ex6(aa:1216) Tier3 1 0.719 2.758 0.01
DNMT3A Ex19(aa:729-741) Tier3 38 0.719 2.796 Resp 0.026
ASXL1 Tier3 4626 0.719 7.422 0.02
RUNX1 Ex8(aa:314-320) Tier2 18 0.719 7.44 0.01
DNMT3A Ex13(aa:497-515) Tier3 54 0.719 7.494 Resp 0.015
PTPN11 Ex13(aa:491-510) Tier3 59 0.719 7.553 0.02

Onco Validated oncogenic  Resp Drug responsive  Resis Drug resistant 


Gene/region Panel tier Cumulative coverage 1 gene Cumulative coverage 2 genes Cumulative coverage 3 genes
NPM1 Ex11(aa:287-288) Tier1 0.265 0.0 0.0
IDH2 Ex4(aa:140-172) Tier1 0.347 0.02 0.0
IDH1 Ex4(aa:132) Tier1 0.398 0.066 0.0
RUNX1 Ex5(aa:141-164) Tier1 0.434 0.071 0.0
DNMT3A Ex23(aa:882-909) Tier1 0.469 0.173 0.015
NRAS Ex3(aa:61) Tier1 0.5 0.173 0.015
FLT3 Ex20(aa:835-839) Tier2 0.526 0.204 0.036
U2AF1 Ex2(aa:34) Tier2 0.546 0.219 0.036
FLT3 Ex14(aa:582-601) Tier2 0.566 0.23 0.041
TP53 Ex6(aa:193-223) Tier2 0.587 0.23 0.041
WT1 Ex7(aa:370-402) Tier2 0.607 0.25 0.041
KIT Ex17(aa:816) Tier2 0.622 0.255 0.041
TP53 Ex8(aa:273-286) Tier2 0.638 0.255 0.041
EZH2 Ex20(aa:744) Tier2 0.643 0.255 0.041
TP53 Ex10(aa:337-342) Tier2 0.653 0.255 0.041
KRAS Tier2 0.663 0.265 0.061
PHF6 Tier2 0.673 0.265 0.077
NRAS Ex2(aa:12-13) Tier2 0.679 0.286 0.087
KIT Ex8(aa:416-418) Tier2 0.684 0.291 0.087
RUNX1 Ex6(aa:198-201) Tier2 0.689 0.306 0.097
TET2 Ex11(aa:1863-1868) Tier2 0.694 0.311 0.097
TP53 Ex5(aa:172-179) Tier2 0.699 0.321 0.097
TET2 Ex7(aa:1307-1316) Tier2 0.704 0.321 0.102
PTPN11 Ex3(aa:60-72) Tier2 0.709 0.327 0.107
TET2 Ex10(aa:1422-1452) Tier2 0.714 0.332 0.107
DNMT3A Ex20(aa:781-792) Tier3 0.719 0.388 0.148
TET2 Ex9(aa:1352-1381) Tier3 0.719 0.393 0.163
DNMT3A Ex15(aa:590-615) Tier3 0.719 0.393 0.153
TET2 Ex3(aa:916-947) Tier3 0.719 0.388 0.148
TET2 Ex6(aa:1216) Tier3 0.719 0.347 0.112
DNMT3A Ex19(aa:729-741) Tier3 0.719 0.372 0.128
ASXL1 Tier3 0.719 0.383 0.143
RUNX1 Ex8(aa:314-320) Tier2 0.719 0.337 0.112
DNMT3A Ex13(aa:497-515) Tier3 0.719 0.372 0.138
PTPN11 Ex13(aa:491-510) Tier3 0.719 0.362 0.117

* Gene with high density mutation hotspots identified


Gene Exon Protein coords Bp length Mutations count Mutations proportion CDS proportion Genomic coords
KIT Ex17 816 2 5 0.714 0.001 chr4:55599320
KIT Ex8 416-418 6 3 0.429 0.002 chr4:55589766-55589771
RUNX1 Ex5 141-164 71 8 0.5 0.049 chr21:36252870-36252940
RUNX1 Ex6 198-201 11 6 0.375 0.008 chr21:36231782-36231792
RUNX1 Ex8 314-320 18 2 0.125 0.012 chr21:36171607-36171624
U2AF1 Ex2 34 1 7 0.875 0.001 chr21:44524456
EZH2 Ex20 744 2 2 1.0 0.001 chr7:148504763
IDH1 Ex4 132 2 19 1.0 0.002 chr2:209113112
PTPN11 Ex3 60-72 37 4 0.444 0.021 chr12:112888163-112888199
FLT3 Ex20 835-839 14 17 0.68 0.005 chr13:28592629-28592642
FLT3 Ex14 582-601 59 7 0.28 0.02 chr13:28608254-28608312
DNMT3A Ex23 882-909 83 30 0.612 0.03 chr2:25457161-25457243
NRAS Ex2 12-13 4 8 0.533 0.007 chr1:115258744-115258747
NRAS Ex3 61 3 6 0.4 0.005 chr1:115256528
IDH2 Ex4 140-172 97 20 1.0 0.071 chr15:90631838-90631934
TET2 Ex10 1422-1452 91 4 0.235 0.015 chr4:106193802-106193892
TET2 Ex11 1863-1868 15 2 0.118 0.002 chr4:106197255-106197269
TET2 Ex7 1307-1316 27 2 0.118 0.004 chr4:106180893-106180919
WT1 Ex7 370-402 97 8 0.8 0.062 chr11:32417846-32417942
TP53 Ex6 193-223 91 4 0.308 0.077 chr17:7578182-7578272
TP53 Ex8 273-286 41 3 0.231 0.035 chr17:7577081-7577121
TP53 Ex5 172-179 21 3 0.231 0.018 chr17:7578394-7578414
TP53 Ex10 337-342 16 2 0.154 0.014 chr17:7574003-7574018
NPM1 Ex11 287-288 5 52 0.963 0.006 chr5:170837544-170837548

* Gene with high density mutation regions identified


Gene Exon Protein coords Bp length Mutations count Mutations proportion CDS proportion Genomic coords
KIT Ex17 816 2 5 0.714 0.001 chr4:55599320
KIT Ex8 416-418 6 3 0.429 0.002 chr4:55589766-55589771
RUNX1 Ex5 141-164 71 8 0.5 0.049 chr21:36252870-36252940
RUNX1 Ex6 198-201 11 6 0.375 0.008 chr21:36231782-36231792
RUNX1 Ex8 314-320 18 2 0.125 0.012 chr21:36171607-36171624
U2AF1 Ex2 34 1 7 0.875 0.001 chr21:44524456
EZH2 Ex20 744 2 2 1.0 0.001 chr7:148504763
IDH1 Ex4 132 2 19 1.0 0.002 chr2:209113112
PTPN11 Ex3 60-72 37 4 0.444 0.021 chr12:112888163-112888199
FLT3 Ex20 835-839 14 17 0.68 0.005 chr13:28592629-28592642
FLT3 Ex14 582-601 59 7 0.28 0.02 chr13:28608254-28608312
DNMT3A Ex23 882-909 83 30 0.612 0.03 chr2:25457161-25457243
NRAS Ex2 12-13 4 8 0.533 0.007 chr1:115258744-115258747
NRAS Ex3 61 3 6 0.4 0.005 chr1:115256528
IDH2 Ex4 140-172 97 20 1.0 0.071 chr15:90631838-90631934
TET2 Ex10 1422-1452 91 4 0.235 0.015 chr4:106193802-106193892
TET2 Ex11 1863-1868 15 2 0.118 0.002 chr4:106197255-106197269
TET2 Ex7 1307-1316 27 2 0.118 0.004 chr4:106180893-106180919
WT1 Ex7 370-402 97 8 0.8 0.062 chr11:32417846-32417942
TP53 Ex6 193-223 91 4 0.308 0.077 chr17:7578182-7578272
TP53 Ex8 273-286 41 3 0.231 0.035 chr17:7577081-7577121
TP53 Ex5 172-179 21 3 0.231 0.018 chr17:7578394-7578414
TP53 Ex10 337-342 16 2 0.154 0.014 chr17:7574003-7574018
NPM1 Ex11 287-288 5 52 0.963 0.006 chr5:170837544-170837548

Gene/region Panel tier Mutation Mutation type Drugs Number of mutated tumors Fraction of mutated tumors
DNMT3A Ex23(aa:882-909) Tier1 DNMT3A oncogenic mutation Drug responsive Daunorubicin (Chemotherapy) 30 1.0
EZH2 Ex20(aa:744) Tier2 EZH2 oncogenic mutation Drug responsive EPZ-6438 (EZH2 inhibitor) 1 1.0
IDH1 Ex4(aa:132) Tier1 IDH1 oncogenic mutation Drug responsive AG-120 (IDH1 inhibitor) 19 1.0
IDH1 Ex4(aa:132) Tier1 IDH1 oncogenic mutation Drug responsive BCL2 inhibitors 19 1.0
IDH1 Ex4(aa:132) Tier1 IDH1 oncogenic mutation Drug responsive Dasatinib (BCR-ABL inhibitor 2nd gen) 19 1.0
IDH1 Ex4(aa:132) Tier1 IDH1 oncogenic mutation Drug responsive IDH1 inhibitors 19 1.0
IDH2 Ex4(aa:140-172) Tier1 IDH2 oncogenic mutation Drug responsive Dasatinib (BCR-ABL inhibitor 2nd gen) 20 1.0
KRAS Tier2 KRAS oncogenic mutation Drug resistant Cetuximab (EGFR mAb inhibitor) 8 1.0
KRAS Tier2 KRAS oncogenic mutation Drug resistant EGFR inhibitor 1st gens 8 1.0
KRAS Tier2 KRAS oncogenic mutation Drug resistant EGFR inhibitor 2nd gens 8 1.0
KRAS Tier2 KRAS oncogenic mutation Drug resistant EGFR inhibitors 8 1.0
KRAS Tier2 KRAS oncogenic mutation Drug resistant EGFR mAb inhibitors 8 1.0
KRAS Tier2 KRAS oncogenic mutation Drug resistant EZH2 inhibitors 8 1.0
KRAS Tier2 KRAS oncogenic mutation Drug resistant PI3K pathway inhibitor + MEK inhibitors 8 1.0
KRAS Tier2 KRAS oncogenic mutation Drug resistant PI3K pathway inhibitors 8 1.0
KRAS Tier2 KRAS oncogenic mutation Drug resistant Panitumumab (EGFR mAb inhibitor) 8 1.0
KRAS Tier2 KRAS oncogenic mutation Drug resistant Regorafenib (Pan-kinase inhibitor) 8 1.0
KRAS Tier2 KRAS oncogenic mutation Drug resistant Selumetinib (MEK inhibitor) 8 1.0
KRAS Tier2 KRAS oncogenic mutation Drug resistant Trastuzumab + Lapatinib (ERBB2 mAb inhibitor + ERBB2 inhibitor) 8 1.0
KRAS Tier2 KRAS oncogenic mutation Drug responsive BET inhibitors 8 1.0
KRAS Tier2 KRAS oncogenic mutation Drug responsive CDK4 inhibitors 8 1.0
KRAS Tier2 KRAS oncogenic mutation Drug responsive CDK4/6 inhibitors (Palbociclib,Abemaciclib,etc) 8 1.0
KRAS Tier2 KRAS oncogenic mutation Drug responsive Decitabine + BCL2 inhibitor (Chemotherapy + BCL2 inhibitor) 8 1.0
KRAS Tier2 KRAS oncogenic mutation Drug responsive Defactinib (Pan-kinase inhibitor) 8 1.0
KRAS Tier2 KRAS oncogenic mutation Drug responsive EGFR mAb inhibitor + MEK inhibitors 8 1.0
KRAS Tier2 KRAS oncogenic mutation Drug responsive ERK inhibitors 8 1.0
KRAS Tier2 KRAS oncogenic mutation Drug responsive FAK inhibitors 8 1.0
KRAS Tier2 KRAS oncogenic mutation Drug responsive FAS inhibitors 8 1.0
KRAS Tier2 KRAS oncogenic mutation Drug responsive Gemcitabine + MEK inhibitor (Chemotherapy + MEK inhibitor) 8 1.0
KRAS Tier2 KRAS oncogenic mutation Drug responsive HSP90 inhibitor (in combination)s 8 1.0
KRAS Tier2 KRAS oncogenic mutation Drug responsive JAK/TBK1/IKKε inhibitors 8 1.0
KRAS Tier2 KRAS oncogenic mutation Drug responsive MEK inhibitor + BCL-XL inhibitors 8 1.0
KRAS Tier2 KRAS oncogenic mutation Drug responsive MEK inhibitor + IGF1R inhibitors 8 1.0
KRAS Tier2 KRAS oncogenic mutation Drug responsive MEK inhibitor + PI3K pathway inhibitors 8 1.0
KRAS Tier2 KRAS oncogenic mutation Drug responsive MEK inhibitors 8 1.0
KRAS Tier2 KRAS oncogenic mutation Drug responsive MTOR inhibitor + BH3 mimeticss 8 1.0
KRAS Tier2 KRAS oncogenic mutation Drug responsive PI3K pathway inhibitor + MEK inhibitors 8 1.0
KRAS Tier2 KRAS oncogenic mutation Drug responsive Selumetinib (MEK inhibitor) 8 1.0
KRAS Tier2 KRAS oncogenic mutation Drug responsive Sorafenib + MEK inhibitor (Pan-TK inhibitor + MEK inhibitor) 8 1.0
KRAS Tier2 KRAS oncogenic mutation Drug responsive pan-RAF inhibitors 8 1.0
NPM1 Ex11(aa:287-288) Tier1 NPM1 oncogenic mutation Drug responsive Daunorubicin (Chemotherapy) 52 1.0
NRAS Ex2(aa:12-13) Tier2 NRAS oncogenic mutation Drug resistant Cetuximab (EGFR mAb inhibitor) 8 1.0
NRAS Ex2(aa:12-13) Tier2 NRAS oncogenic mutation Drug resistant Panitumumab (EGFR mAb inhibitor) 8 1.0
NRAS Ex2(aa:12-13) Tier2 NRAS oncogenic mutation Drug resistant Vemurafenib (BRAF inhibitor) 8 1.0
NRAS Ex2(aa:12-13) Tier2 NRAS oncogenic mutation Drug responsive CDK4/6 inhibitor + MEK inhibitors 8 1.0
NRAS Ex2(aa:12-13) Tier2 NRAS oncogenic mutation Drug responsive MEK inhibitor +/- PI3K pathway inhibitors 8 1.0
NRAS Ex2(aa:12-13) Tier2 NRAS oncogenic mutation Drug responsive MEK inhibitors 8 1.0
NRAS Ex2(aa:12-13) Tier2 NRAS oncogenic mutation Drug responsive PI3K pathway inhibitor + MEK inhibitors 8 1.0
NRAS Ex2(aa:12-13) Tier2 NRAS oncogenic mutation Drug responsive Sorafenib + MEK inhibitor (Pan-TK inhibitor + MEK inhibitor) 8 1.0
NRAS Ex3(aa:61) Tier1 NRAS oncogenic mutation Drug resistant Cetuximab (EGFR mAb inhibitor) 6 1.0
NRAS Ex3(aa:61) Tier1 NRAS oncogenic mutation Drug resistant Panitumumab (EGFR mAb inhibitor) 6 1.0
NRAS Ex3(aa:61) Tier1 NRAS oncogenic mutation Drug resistant Vemurafenib (BRAF inhibitor) 6 1.0
NRAS Ex3(aa:61) Tier1 NRAS oncogenic mutation Drug responsive CDK4/6 inhibitor + MEK inhibitors 6 1.0
NRAS Ex3(aa:61) Tier1 NRAS oncogenic mutation Drug responsive MEK inhibitor +/- PI3K pathway inhibitors 6 1.0
NRAS Ex3(aa:61) Tier1 NRAS oncogenic mutation Drug responsive MEK inhibitors 6 1.0
NRAS Ex3(aa:61) Tier1 NRAS oncogenic mutation Drug responsive PI3K pathway inhibitor + MEK inhibitors 6 1.0
NRAS Ex3(aa:61) Tier1 NRAS oncogenic mutation Drug responsive Sorafenib + MEK inhibitor (Pan-TK inhibitor + MEK inhibitor) 6 1.0
TP53 Ex10(aa:337-342) Tier2 TP53 oncogenic mutation Drug resistant MDM2 inhibitors 2 1.0
TP53 Ex10(aa:337-342) Tier2 TP53 oncogenic mutation Drug responsive AZD6738 (ATR inhibitor) 2 1.0
TP53 Ex10(aa:337-342) Tier2 TP53 oncogenic mutation Drug responsive Lenalidomide (Immunomodulator) 2 1.0
TP53 Ex10(aa:337-342) Tier2 TP53 oncogenic mutation Drug responsive MK-1775 (WEE1 inhibitor) 2 1.0
TP53 Ex10(aa:337-342) Tier2 TP53 oncogenic mutation Drug responsive Pramlintide (Amylin analogue) 2 1.0
TP53 Ex10(aa:337-342) Tier2 TP53 oncogenic mutation Drug responsive WEE1 inhibitors 2 1.0
TP53 Ex5(aa:172-179) Tier2 TP53 oncogenic mutation Drug resistant MDM2 inhibitors 3 1.0
TP53 Ex5(aa:172-179) Tier2 TP53 oncogenic mutation Drug responsive AZD6738 (ATR inhibitor) 3 1.0
TP53 Ex5(aa:172-179) Tier2 TP53 oncogenic mutation Drug responsive Lenalidomide (Immunomodulator) 3 1.0
TP53 Ex5(aa:172-179) Tier2 TP53 oncogenic mutation Drug responsive MK-1775 (WEE1 inhibitor) 3 1.0
TP53 Ex5(aa:172-179) Tier2 TP53 oncogenic mutation Drug responsive Pramlintide (Amylin analogue) 3 1.0
TP53 Ex5(aa:172-179) Tier2 TP53 oncogenic mutation Drug responsive WEE1 inhibitors 3 1.0
TP53 Ex6(aa:193-223) Tier2 TP53 oncogenic mutation Drug resistant MDM2 inhibitors 4 1.0
TP53 Ex6(aa:193-223) Tier2 TP53 oncogenic mutation Drug responsive AZD6738 (ATR inhibitor) 4 1.0
TP53 Ex6(aa:193-223) Tier2 TP53 oncogenic mutation Drug responsive Lenalidomide (Immunomodulator) 4 1.0
TP53 Ex6(aa:193-223) Tier2 TP53 oncogenic mutation Drug responsive MK-1775 (WEE1 inhibitor) 4 1.0
TP53 Ex6(aa:193-223) Tier2 TP53 oncogenic mutation Drug responsive Pramlintide (Amylin analogue) 4 1.0
TP53 Ex6(aa:193-223) Tier2 TP53 oncogenic mutation Drug responsive WEE1 inhibitors 4 1.0
TP53 Ex8(aa:273-286) Tier2 TP53 oncogenic mutation Drug resistant MDM2 inhibitors 3 1.0
TP53 Ex8(aa:273-286) Tier2 TP53 oncogenic mutation Drug responsive AZD6738 (ATR inhibitor) 3 1.0
TP53 Ex8(aa:273-286) Tier2 TP53 oncogenic mutation Drug responsive Lenalidomide (Immunomodulator) 3 1.0
TP53 Ex8(aa:273-286) Tier2 TP53 oncogenic mutation Drug responsive MK-1775 (WEE1 inhibitor) 3 1.0
TP53 Ex8(aa:273-286) Tier2 TP53 oncogenic mutation Drug responsive Pramlintide (Amylin analogue) 3 1.0
TP53 Ex8(aa:273-286) Tier2 TP53 oncogenic mutation Drug responsive WEE1 inhibitors 3 1.0


Gene Panel tier Driver mode of action Driver source Major driver
KRAS Tier2 Activating Rubio-Perez&Tamborero(2015), CGC, Validated somatic mutation list
PHF6 Tier2 Loss of function Rubio-Perez&Tamborero(2015)
DNMT3A Tier1 Loss of function Validated somatic mutation list, Rubio-Perez&Tamborero(2015), CGC
EZH2 Tier2 Loss of function Rubio-Perez&Tamborero(2015)
FLT3 Tier2 Activating Validated somatic mutation list, Rubio-Perez&Tamborero(2015), CGC
IDH1 Tier1 Activating Validated somatic mutation list, Rubio-Perez&Tamborero(2015)
IDH2 Tier1 Activating Validated somatic mutation list, Rubio-Perez&Tamborero(2015)
KIT Tier2 Activating Validated somatic mutation list, Rubio-Perez&Tamborero(2015), CGC
NPM1 Tier1 Loss of function Validated somatic mutation list, Rubio-Perez&Tamborero(2015), CGC
NRAS Tier1&Tier2 Activating Validated somatic mutation list, Rubio-Perez&Tamborero(2015), CGC
PTPN11 Tier2 Activating Rubio-Perez&Tamborero(2015), CGC
RUNX1 Tier1&Tier2 Loss of function Validated somatic mutation list, Rubio-Perez&Tamborero(2015)
TET2 Tier2 Loss of function Rubio-Perez&Tamborero(2015)
TP53 Tier2 Loss of function Validated somatic mutation list, Rubio-Perez&Tamborero(2015)
U2AF1 Tier2 Activating Validated somatic mutation list, Rubio-Perez&Tamborero(2015)
WT1 Tier2 Loss of function Validated somatic mutation list, Rubio-Perez&Tamborero(2015)