Cancer Hotspots

Overview

Cancer Hotspots, a resource for statistically significant mutations in cancer. It provides information about statistically significantly recurrent mutations identified in large scale cancer genomics data.

Publication

Chang MT, Bhattarai TS, Schram AM, Bielski CM, Donoghue MTA, Jonsson P, Chakravarty D, Phillips S, Kandoth C, Penson A, Gorelick A, Shamu T, Patel S, Harris C, Gao J, Sumer SO, Kundra R, Razavi P, Li BT, Reales DN, Socci ND, Jayakumaran G, Zehir A, Benayed R, Arcila ME, Chandarlapaty S, Ladanyi M, Schultz N, Baselga J, Berger MF, Rosen N, Solit DB, Hyman DM, Taylor BS. Accelerating Discovery of Functional Mutant Alleles in Cancer. Cancer Discov. 2018 Feb;8(2):174-183. doi: 10.1158/2159-8290.CD-17-0321. Epub 2017 Dec 15. PMID: 29247016; PMCID: PMC5809279.

Chang MT, Asthana S, Gao SP, Lee BH, Chapman JS, Kandoth C, Gao J, Socci ND, Solit DB, Olshen AB, Schultz N, Taylor BS. Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity. Nat Biotechnol. 2016 Feb;34(2):155-63. doi: 10.1038/nbt.3391. Epub 2015 Nov 30. PMID: 26619011; PMCID: PMC4744099.

Data extraction

Illumina Connected Annotations currently parses SNV and indel tabs from hotspots_v2.xls file to extract the relevant content.

Example

SNV

Hugo_Symbol     Amino_Acid_Position     log10_pvalue    Mutation_Count  Reference_Amino_Acid    Total_Mutations_in_Gene Median_Allele_Freq_Rank Allele_Freq_Rank        Variant_Amino_Acid   Codon_Change     Genomic_Position        Detailed_Cancer_Types   Organ_Types     Tri-nucleotides Mutability      mu_protein      Total_Samples   Analysis_Type   qvalue  tm      qvalue_pancanIs_repeat        seq     length  align100        pad12entropy    pad24entropy    pad36entropy    TP      reason  n_MSK   n_Retro judgement       inNBT   inOncokb        ref     qvaluect     ct       Samples
NRAS    61      -1237.69143477067       422     Q:422   620     0.333333333333333       295|0.692307692307692:0.733333333333333:0.2:0.933333333333333:1:0.25:0.666666666666667:1:0.25:0.571428571428571:1:1:0.5:0.363636363636364:0.428571428571429:0.0833333333333333:1:1:1:1:0.5:1:0.125:0.363636363636364:0.173913043478261:0.25:1:0.8:0.153846153846154:0.857142857142857:0.5:0.5:0.5:1:0.272727272727273:0.214285714285714:1:0.5:1:1:0.2:0.333333333333333:0.6875:0.708333333333333:0.25:0.266666666666667:0.111111111111111:1:1:0.333333333333333:0.428571428571429:0.666666666666667:0.25:0.5:0.833333333333333:0.5:0.735294117647059:0.0476190476190476:0.1:0.133333333333333:0.230769230769231:0.25:1:0.5:0.294117647058824:0.217391304347826:0.46875:0.5:1:0.2:0.166666666666667:0.666666666666667:1:0.8:0.407407407407407:1:0.0212765957446809:0.285714285714286:0.0909090909090909:0.333333333333333:0.2:0.333333333333333:0.5:0.5:1:0.111111111111111:0.5:0.903846153846154:0.5:0.2:1:1:0.0909090909090909:0.4:0.428571428571429:0.0625:0.25:0.833333333333333:1:0.956521739130435:0.111111111111111:0.6:0.212765957446809:0.5:0.207547169811321:1:0.75:0.294117647058824:0.666666666666667:1:0.333333333333333:0.714285714285714:0.142857142857143:1:0.3:0.416666666666667:0.272727272727273:0.25:0.333333333333333:0.345454545454545:0.0952380952380952:0.166666666666667:0.111111111111111:0.454545454545455:0.0666666666666667:1:0.636363636363636:0.636363636363636:0.25:0.272727272727273:0.824324324324324:1:0.75:0.545454545454545:1:1:0.0769230769230769:0.363636363636364:0.290322580645161:0.333333333333333:0.179487179487179:1:0.0666666666666667:0.333333333333333:1:0.478260869565217:0.166666666666667:1:1:0.0276497695852535:0.0716845878136201:0.0263736263736264:0.933333333333333:1:0.5:1:1:0.8125:0.361788617886179:0.113761467889908:0.113761467889908:0.157894736842105:0.333333333333333:0.0555555555555556:0.0357142857142857:0.375:0.111111111111111:0.584415584415584:0.0350877192982456:0.751111111111111:0.761245674740484:0.164989939637827:0.196652719665272:0.135549872122762:0.172113289760349:0.0240963855421687:0.0620767494356659:0.142268041237113:0.147441457068517:0.147959183673469:0.038961038961039:0.686274509803922:0.0929054054054054:0.364787111622555:0.331306990881459:0.691449814126394:0.691449814126394:0.0769230769230769:0.347826086956522:0.117647058823529:0.148148148148148:0.05:0.290030211480363:0.680272108843537:0.188679245283019:0.0701754385964912:0.801526717557252:0.236842105263158:0.1953125:0.0539906103286385:0.015625:0.0390492359932088:0.00790513833992095:0.0597826086956522:0.136783733826248:0.362359550561798:0.0713719270420301:0.328621908127208:0.0657672849915683:0.320099255583127:0.075:0.433021806853583:0.524818401937046:0.524818401937046:0.259259259259259:0.483695652173913:0.0269360269360269:0.100486223662885:0.785507246376812:0.137870855148342:0.472340425531915:0.194331983805668:0.0830769230769231:0.418055555555556:0.546296296296296:0.247596153846154:0.52:0.39832285115304:0.601866251944012:0.234016887816647:0.214007782101167:0.153153153153153:0.137180700094607:0.0666666666666667:0.037037037037037:0.1:0.2:0.458333333333333:0.0588235294117647:0.111111111111111:0.333333333333333:0.181818181818182:0.473684210526316:0.5:0.2:0.136363636363636:0.0769230769230769:0.142857142857143:0.285714285714286:0.25:0.445714285714286:0.149377593360996:0.0227790432801822:0.182278481012658:0.540123456790123:0.021505376344086:0.541666666666667:0.00429184549356223:0.473684210526316:0.103508771929825:0.0930232558139535:0.391304347826087:0.072:0.0113636363636364:0.148837209302326:0.448051948051948:0.761038961038961:0.530373831775701:0.222857142857143:0.433862433862434:0.0810810810810811:0.0723327305605787:0.410714285714286:0.247910863509749:0.384615384615385:0.125:0.24:0.783582089552239:0.0646651270207852:0.445569620253165:0.754777070063694:0.165137614678899:0.10732538330494:0.0375:0.538461538461538:0.0981387478849408:0.029126213592233:0.0833333333333333:0.443514644351464:0.0917431192660551:0.03125:0.674418604651163:0.3125:0.375:0.314285714285714     R:204   cAa/cGa:203|Caa/Aaa:140|cAa/cTa:46|caA/caT:14|caA/caC:13|ggACaa/ggCAaa:2|cAa/cCa:2|Caa/Taa:1|CAa/AGa:1  1:115256529_252|1:115256530_143|1:115256528_27        skcm:787:186|thpa:486:43|mm:275:27|thpd:58:18|coadread:683:16|luad:2057:15|coad:712:13|mup:42:7|aml:198:6|blca:852:5|thap:33:5|read:149:5|rms:50:5|uec:339:5|nsgct:152:5|cll:283:4|ihch:104:4|lgsoc:17:3|sem:59:3|thhc:21:3|erms:8:3|lggnos:544:3|utuc:76:2|cup:135:2|thfo:5:2|sarcl:13:2|mfh:53:2|gbm:688:2|soc:468:2|stad:748:2|thym:125:2|es:229:1|npc:66:1|unk:146:1|panet:86:1|hnsc:643:1|armm:21:1|tmt:3:1|acrm:23:1|thyc:9:1|odg:36:1|paasc:8:1|hnmucm:11:1|blad:7:1|esca:556:1|mixed:3:1|chol:152:1|hcc:620:1|sarc:280:1|chrcc:88:1|aca:93:1     skin:974:187|thyroid:618:71|blood:890:37|bowel:1782:35|lung:2761:17|unk:357:11|softtissue:739:11|testis:217:9|bladder:958:8|cnsbrain:2270:6|ovaryfallopiantube:699:5|biliarytract:358:5|uterus:618:5|headandneck:988:3|thymus:162:3|esophagusstomach:1407:3|pancreas:1059:2|bone:297:1|liver:636:1|kidney:1304:1|adrenalgland:291:1    TTG|ACA|CTT|TCG|CCC|CCA 0.0120300464273379      0.0267810594223141    24592   "pancan,skin,thyroid,bowel,blood,lung,softtissue,testis,bladder,cnsbrain,biliarytract,ovaryfallopiantube,uterus,thymus,headandneck,esophagusstomach"    0       NRAS 61       0       FALSE           NA      1       1.16795714944678        1.26187131041539        1.29838371117394        TRUE            165     257     RETAIN  TRUE    TRUE    Q       0    skin     skin:88|thyroid:54|blood:15|bowel:8|testis:5|biliarytract:4|bladder:4|lung:4|ovaryfallopiantube:4|softtissue:3|unk:3|uterus:3|cnsbrain:2|esophagusstomach:2|headandneck:2|bone:1|pancreas:1|thymus:1
NRAS    61      -1237.69143477067       422     Q:422   620     0.333333333333333       295|0.692307692307692:0.733333333333333:0.2:0.933333333333333:1:0.25:0.666666666666667:1:0.25:0.571428571428571:1:1:0.5:0.363636363636364:0.428571428571429:0.0833333333333333:1:1:1:1:0.5:1:0.125:0.363636363636364:0.173913043478261:0.25:1:0.8:0.153846153846154:0.857142857142857:0.5:0.5:0.5:1:0.272727272727273:0.214285714285714:1:0.5:1:1:0.2:0.333333333333333:0.6875:0.708333333333333:0.25:0.266666666666667:0.111111111111111:1:1:0.333333333333333:0.428571428571429:0.666666666666667:0.25:0.5:0.833333333333333:0.5:0.735294117647059:0.0476190476190476:0.1:0.133333333333333:0.230769230769231:0.25:1:0.5:0.294117647058824:0.217391304347826:0.46875:0.5:1:0.2:0.166666666666667:0.666666666666667:1:0.8:0.407407407407407:1:0.0212765957446809:0.285714285714286:0.0909090909090909:0.333333333333333:0.2:0.333333333333333:0.5:0.5:1:0.111111111111111:0.5:0.903846153846154:0.5:0.2:1:1:0.0909090909090909:0.4:0.428571428571429:0.0625:0.25:0.833333333333333:1:0.956521739130435:0.111111111111111:0.6:0.212765957446809:0.5:0.207547169811321:1:0.75:0.294117647058824:0.666666666666667:1:0.333333333333333:0.714285714285714:0.142857142857143:1:0.3:0.416666666666667:0.272727272727273:0.25:0.333333333333333:0.345454545454545:0.0952380952380952:0.166666666666667:0.111111111111111:0.454545454545455:0.0666666666666667:1:0.636363636363636:0.636363636363636:0.25:0.272727272727273:0.824324324324324:1:0.75:0.545454545454545:1:1:0.0769230769230769:0.363636363636364:0.290322580645161:0.333333333333333:0.179487179487179:1:0.0666666666666667:0.333333333333333:1:0.478260869565217:0.166666666666667:1:1:0.0276497695852535:0.0716845878136201:0.0263736263736264:0.933333333333333:1:0.5:1:1:0.8125:0.361788617886179:0.113761467889908:0.113761467889908:0.157894736842105:0.333333333333333:0.0555555555555556:0.0357142857142857:0.375:0.111111111111111:0.584415584415584:0.0350877192982456:0.751111111111111:0.761245674740484:0.164989939637827:0.196652719665272:0.135549872122762:0.172113289760349:0.0240963855421687:0.0620767494356659:0.142268041237113:0.147441457068517:0.147959183673469:0.038961038961039:0.686274509803922:0.0929054054054054:0.364787111622555:0.331306990881459:0.691449814126394:0.691449814126394:0.0769230769230769:0.347826086956522:0.117647058823529:0.148148148148148:0.05:0.290030211480363:0.680272108843537:0.188679245283019:0.0701754385964912:0.801526717557252:0.236842105263158:0.1953125:0.0539906103286385:0.015625:0.0390492359932088:0.00790513833992095:0.0597826086956522:0.136783733826248:0.362359550561798:0.0713719270420301:0.328621908127208:0.0657672849915683:0.320099255583127:0.075:0.433021806853583:0.524818401937046:0.524818401937046:0.259259259259259:0.483695652173913:0.0269360269360269:0.100486223662885:0.785507246376812:0.137870855148342:0.472340425531915:0.194331983805668:0.0830769230769231:0.418055555555556:0.546296296296296:0.247596153846154:0.52:0.39832285115304:0.601866251944012:0.234016887816647:0.214007782101167:0.153153153153153:0.137180700094607:0.0666666666666667:0.037037037037037:0.1:0.2:0.458333333333333:0.0588235294117647:0.111111111111111:0.333333333333333:0.181818181818182:0.473684210526316:0.5:0.2:0.136363636363636:0.0769230769230769:0.142857142857143:0.285714285714286:0.25:0.445714285714286:0.149377593360996:0.0227790432801822:0.182278481012658:0.540123456790123:0.021505376344086:0.541666666666667:0.00429184549356223:0.473684210526316:0.103508771929825:0.0930232558139535:0.391304347826087:0.072:0.0113636363636364:0.148837209302326:0.448051948051948:0.761038961038961:0.530373831775701:0.222857142857143:0.433862433862434:0.0810810810810811:0.0723327305605787:0.410714285714286:0.247910863509749:0.384615384615385:0.125:0.24:0.783582089552239:0.0646651270207852:0.445569620253165:0.754777070063694:0.165137614678899:0.10732538330494:0.0375:0.538461538461538:0.0981387478849408:0.029126213592233:0.0833333333333333:0.443514644351464:0.0917431192660551:0.03125:0.674418604651163:0.3125:0.375:0.314285714285714     K:142   cAa/cGa:203|Caa/Aaa:140|cAa/cTa:46|caA/caT:14|caA/caC:13|ggACaa/ggCAaa:2|cAa/cCa:2|Caa/Taa:1|CAa/AGa:1  1:115256529_252|1:115256530_143|1:115256528_27        skcm:787:186|thpa:486:43|mm:275:27|thpd:58:18|coadread:683:16|luad:2057:15|coad:712:13|mup:42:7|aml:198:6|blca:852:5|thap:33:5|read:149:5|rms:50:5|uec:339:5|nsgct:152:5|cll:283:4|ihch:104:4|lgsoc:17:3|sem:59:3|thhc:21:3|erms:8:3|lggnos:544:3|utuc:76:2|cup:135:2|thfo:5:2|sarcl:13:2|mfh:53:2|gbm:688:2|soc:468:2|stad:748:2|thym:125:2|es:229:1|npc:66:1|unk:146:1|panet:86:1|hnsc:643:1|armm:21:1|tmt:3:1|acrm:23:1|thyc:9:1|odg:36:1|paasc:8:1|hnmucm:11:1|blad:7:1|esca:556:1|mixed:3:1|chol:152:1|hcc:620:1|sarc:280:1|chrcc:88:1|aca:93:1     skin:974:187|thyroid:618:71|blood:890:37|bowel:1782:35|lung:2761:17|unk:357:11|softtissue:739:11|testis:217:9|bladder:958:8|cnsbrain:2270:6|ovaryfallopiantube:699:5|biliarytract:358:5|uterus:618:5|headandneck:988:3|thymus:162:3|esophagusstomach:1407:3|pancreas:1059:2|bone:297:1|liver:636:1|kidney:1304:1|adrenalgland:291:1    TTG|ACA|CTT|TCG|CCC|CCA 0.0120300464273379      0.0267810594223141    24592   "pancan,skin,thyroid,bowel,blood,lung,softtissue,testis,bladder,cnsbrain,biliarytract,ovaryfallopiantube,uterus,thymus,headandneck,esophagusstomach"    0       NRAS 61       0       FALSE           NA      1       1.16795714944678        1.26187131041539        1.29838371117394        TRUE            165     257     RETAIN  TRUE    TRUE    Q       0    skin     skin:62|bowel:18|thyroid:17|blood:12|softtissue:6|lung:5|unk:5|bladder:3|cnsbrain:2|thymus:2|adrenalgland:1|biliarytract:1|esophagusstomach:1|headandneck:1|kidney:1|liver:1|ovaryfallopiantube:1|pancreas:1|testis:1|uterus:1
NRAS    61      -1237.69143477067       422     Q:422   620     0.333333333333333       295|0.692307692307692:0.733333333333333:0.2:0.933333333333333:1:0.25:0.666666666666667:1:0.25:0.571428571428571:1:1:0.5:0.363636363636364:0.428571428571429:0.0833333333333333:1:1:1:1:0.5:1:0.125:0.363636363636364:0.173913043478261:0.25:1:0.8:0.153846153846154:0.857142857142857:0.5:0.5:0.5:1:0.272727272727273:0.214285714285714:1:0.5:1:1:0.2:0.333333333333333:0.6875:0.708333333333333:0.25:0.266666666666667:0.111111111111111:1:1:0.333333333333333:0.428571428571429:0.666666666666667:0.25:0.5:0.833333333333333:0.5:0.735294117647059:0.0476190476190476:0.1:0.133333333333333:0.230769230769231:0.25:1:0.5:0.294117647058824:0.217391304347826:0.46875:0.5:1:0.2:0.166666666666667:0.666666666666667:1:0.8:0.407407407407407:1:0.0212765957446809:0.285714285714286:0.0909090909090909:0.333333333333333:0.2:0.333333333333333:0.5:0.5:1:0.111111111111111:0.5:0.903846153846154:0.5:0.2:1:1:0.0909090909090909:0.4:0.428571428571429:0.0625:0.25:0.833333333333333:1:0.956521739130435:0.111111111111111:0.6:0.212765957446809:0.5:0.207547169811321:1:0.75:0.294117647058824:0.666666666666667:1:0.333333333333333:0.714285714285714:0.142857142857143:1:0.3:0.416666666666667:0.272727272727273:0.25:0.333333333333333:0.345454545454545:0.0952380952380952:0.166666666666667:0.111111111111111:0.454545454545455:0.0666666666666667:1:0.636363636363636:0.636363636363636:0.25:0.272727272727273:0.824324324324324:1:0.75:0.545454545454545:1:1:0.0769230769230769:0.363636363636364:0.290322580645161:0.333333333333333:0.179487179487179:1:0.0666666666666667:0.333333333333333:1:0.478260869565217:0.166666666666667:1:1:0.0276497695852535:0.0716845878136201:0.0263736263736264:0.933333333333333:1:0.5:1:1:0.8125:0.361788617886179:0.113761467889908:0.113761467889908:0.157894736842105:0.333333333333333:0.0555555555555556:0.0357142857142857:0.375:0.111111111111111:0.584415584415584:0.0350877192982456:0.751111111111111:0.761245674740484:0.164989939637827:0.196652719665272:0.135549872122762:0.172113289760349:0.0240963855421687:0.0620767494356659:0.142268041237113:0.147441457068517:0.147959183673469:0.038961038961039:0.686274509803922:0.0929054054054054:0.364787111622555:0.331306990881459:0.691449814126394:0.691449814126394:0.0769230769230769:0.347826086956522:0.117647058823529:0.148148148148148:0.05:0.290030211480363:0.680272108843537:0.188679245283019:0.0701754385964912:0.801526717557252:0.236842105263158:0.1953125:0.0539906103286385:0.015625:0.0390492359932088:0.00790513833992095:0.0597826086956522:0.136783733826248:0.362359550561798:0.0713719270420301:0.328621908127208:0.0657672849915683:0.320099255583127:0.075:0.433021806853583:0.524818401937046:0.524818401937046:0.259259259259259:0.483695652173913:0.0269360269360269:0.100486223662885:0.785507246376812:0.137870855148342:0.472340425531915:0.194331983805668:0.0830769230769231:0.418055555555556:0.546296296296296:0.247596153846154:0.52:0.39832285115304:0.601866251944012:0.234016887816647:0.214007782101167:0.153153153153153:0.137180700094607:0.0666666666666667:0.037037037037037:0.1:0.2:0.458333333333333:0.0588235294117647:0.111111111111111:0.333333333333333:0.181818181818182:0.473684210526316:0.5:0.2:0.136363636363636:0.0769230769230769:0.142857142857143:0.285714285714286:0.25:0.445714285714286:0.149377593360996:0.0227790432801822:0.182278481012658:0.540123456790123:0.021505376344086:0.541666666666667:0.00429184549356223:0.473684210526316:0.103508771929825:0.0930232558139535:0.391304347826087:0.072:0.0113636363636364:0.148837209302326:0.448051948051948:0.761038961038961:0.530373831775701:0.222857142857143:0.433862433862434:0.0810810810810811:0.0723327305605787:0.410714285714286:0.247910863509749:0.384615384615385:0.125:0.24:0.783582089552239:0.0646651270207852:0.445569620253165:0.754777070063694:0.165137614678899:0.10732538330494:0.0375:0.538461538461538:0.0981387478849408:0.029126213592233:0.0833333333333333:0.443514644351464:0.0917431192660551:0.03125:0.674418604651163:0.3125:0.375:0.314285714285714     L:46    cAa/cGa:203|Caa/Aaa:140|cAa/cTa:46|caA/caT:14|caA/caC:13|ggACaa/ggCAaa:2|cAa/cCa:2|Caa/Taa:1|CAa/AGa:1  1:115256529_252|1:115256530_143|1:115256528_27        skcm:787:186|thpa:486:43|mm:275:27|thpd:58:18|coadread:683:16|luad:2057:15|coad:712:13|mup:42:7|aml:198:6|blca:852:5|thap:33:5|read:149:5|rms:50:5|uec:339:5|nsgct:152:5|cll:283:4|ihch:104:4|lgsoc:17:3|sem:59:3|thhc:21:3|erms:8:3|lggnos:544:3|utuc:76:2|cup:135:2|thfo:5:2|sarcl:13:2|mfh:53:2|gbm:688:2|soc:468:2|stad:748:2|thym:125:2|es:229:1|npc:66:1|unk:146:1|panet:86:1|hnsc:643:1|armm:21:1|tmt:3:1|acrm:23:1|thyc:9:1|odg:36:1|paasc:8:1|hnmucm:11:1|blad:7:1|esca:556:1|mixed:3:1|chol:152:1|hcc:620:1|sarc:280:1|chrcc:88:1|aca:93:1     skin:974:187|thyroid:618:71|blood:890:37|bowel:1782:35|lung:2761:17|unk:357:11|softtissue:739:11|testis:217:9|bladder:958:8|cnsbrain:2270:6|ovaryfallopiantube:699:5|biliarytract:358:5|uterus:618:5|headandneck:988:3|thymus:162:3|esophagusstomach:1407:3|pancreas:1059:2|bone:297:1|liver:636:1|kidney:1304:1|adrenalgland:291:1    TTG|ACA|CTT|TCG|CCC|CCA 0.0120300464273379      0.0267810594223141    24592   "pancan,skin,thyroid,bowel,blood,lung,softtissue,testis,bladder,cnsbrain,biliarytract,ovaryfallopiantube,uterus,thymus,headandneck,esophagusstomach"    0       NRAS 61       0       FALSE           NA      1       1.16795714944678        1.26187131041539        1.29838371117394        TRUE            165     257     RETAIN  TRUE    TRUE    Q       0    skin     skin:24|bowel:7|lung:6|blood:2|cnsbrain:2|unk:2|bladder:1|softtissue:1|uterus:1
NRAS    61      -1237.69143477067       422     Q:422   620     0.333333333333333       295|0.692307692307692:0.733333333333333:0.2:0.933333333333333:1:0.25:0.666666666666667:1:0.25:0.571428571428571:1:1:0.5:0.363636363636364:0.428571428571429:0.0833333333333333:1:1:1:1:0.5:1:0.125:0.363636363636364:0.173913043478261:0.25:1:0.8:0.153846153846154:0.857142857142857:0.5:0.5:0.5:1:0.272727272727273:0.214285714285714:1:0.5:1:1:0.2:0.333333333333333:0.6875:0.708333333333333:0.25:0.266666666666667:0.111111111111111:1:1:0.333333333333333:0.428571428571429:0.666666666666667:0.25:0.5:0.833333333333333:0.5:0.735294117647059:0.0476190476190476:0.1:0.133333333333333:0.230769230769231:0.25:1:0.5:0.294117647058824:0.217391304347826:0.46875:0.5:1:0.2:0.166666666666667:0.666666666666667:1:0.8:0.407407407407407:1:0.0212765957446809:0.285714285714286:0.0909090909090909:0.333333333333333:0.2:0.333333333333333:0.5:0.5:1:0.111111111111111:0.5:0.903846153846154:0.5:0.2:1:1:0.0909090909090909:0.4:0.428571428571429:0.0625:0.25:0.833333333333333:1:0.956521739130435:0.111111111111111:0.6:0.212765957446809:0.5:0.207547169811321:1:0.75:0.294117647058824:0.666666666666667:1:0.333333333333333:0.714285714285714:0.142857142857143:1:0.3:0.416666666666667:0.272727272727273:0.25:0.333333333333333:0.345454545454545:0.0952380952380952:0.166666666666667:0.111111111111111:0.454545454545455:0.0666666666666667:1:0.636363636363636:0.636363636363636:0.25:0.272727272727273:0.824324324324324:1:0.75:0.545454545454545:1:1:0.0769230769230769:0.363636363636364:0.290322580645161:0.333333333333333:0.179487179487179:1:0.0666666666666667:0.333333333333333:1:0.478260869565217:0.166666666666667:1:1:0.0276497695852535:0.0716845878136201:0.0263736263736264:0.933333333333333:1:0.5:1:1:0.8125:0.361788617886179:0.113761467889908:0.113761467889908:0.157894736842105:0.333333333333333:0.0555555555555556:0.0357142857142857:0.375:0.111111111111111:0.584415584415584:0.0350877192982456:0.751111111111111:0.761245674740484:0.164989939637827:0.196652719665272:0.135549872122762:0.172113289760349:0.0240963855421687:0.0620767494356659:0.142268041237113:0.147441457068517:0.147959183673469:0.038961038961039:0.686274509803922:0.0929054054054054:0.364787111622555:0.331306990881459:0.691449814126394:0.691449814126394:0.0769230769230769:0.347826086956522:0.117647058823529:0.148148148148148:0.05:0.290030211480363:0.680272108843537:0.188679245283019:0.0701754385964912:0.801526717557252:0.236842105263158:0.1953125:0.0539906103286385:0.015625:0.0390492359932088:0.00790513833992095:0.0597826086956522:0.136783733826248:0.362359550561798:0.0713719270420301:0.328621908127208:0.0657672849915683:0.320099255583127:0.075:0.433021806853583:0.524818401937046:0.524818401937046:0.259259259259259:0.483695652173913:0.0269360269360269:0.100486223662885:0.785507246376812:0.137870855148342:0.472340425531915:0.194331983805668:0.0830769230769231:0.418055555555556:0.546296296296296:0.247596153846154:0.52:0.39832285115304:0.601866251944012:0.234016887816647:0.214007782101167:0.153153153153153:0.137180700094607:0.0666666666666667:0.037037037037037:0.1:0.2:0.458333333333333:0.0588235294117647:0.111111111111111:0.333333333333333:0.181818181818182:0.473684210526316:0.5:0.2:0.136363636363636:0.0769230769230769:0.142857142857143:0.285714285714286:0.25:0.445714285714286:0.149377593360996:0.0227790432801822:0.182278481012658:0.540123456790123:0.021505376344086:0.541666666666667:0.00429184549356223:0.473684210526316:0.103508771929825:0.0930232558139535:0.391304347826087:0.072:0.0113636363636364:0.148837209302326:0.448051948051948:0.761038961038961:0.530373831775701:0.222857142857143:0.433862433862434:0.0810810810810811:0.0723327305605787:0.410714285714286:0.247910863509749:0.384615384615385:0.125:0.24:0.783582089552239:0.0646651270207852:0.445569620253165:0.754777070063694:0.165137614678899:0.10732538330494:0.0375:0.538461538461538:0.0981387478849408:0.029126213592233:0.0833333333333333:0.443514644351464:0.0917431192660551:0.03125:0.674418604651163:0.3125:0.375:0.314285714285714     H:27    cAa/cGa:203|Caa/Aaa:140|cAa/cTa:46|caA/caT:14|caA/caC:13|ggACaa/ggCAaa:2|cAa/cCa:2|Caa/Taa:1|CAa/AGa:1  1:115256529_252|1:115256530_143|1:115256528_27        skcm:787:186|thpa:486:43|mm:275:27|thpd:58:18|coadread:683:16|luad:2057:15|coad:712:13|mup:42:7|aml:198:6|blca:852:5|thap:33:5|read:149:5|rms:50:5|uec:339:5|nsgct:152:5|cll:283:4|ihch:104:4|lgsoc:17:3|sem:59:3|thhc:21:3|erms:8:3|lggnos:544:3|utuc:76:2|cup:135:2|thfo:5:2|sarcl:13:2|mfh:53:2|gbm:688:2|soc:468:2|stad:748:2|thym:125:2|es:229:1|npc:66:1|unk:146:1|panet:86:1|hnsc:643:1|armm:21:1|tmt:3:1|acrm:23:1|thyc:9:1|odg:36:1|paasc:8:1|hnmucm:11:1|blad:7:1|esca:556:1|mixed:3:1|chol:152:1|hcc:620:1|sarc:280:1|chrcc:88:1|aca:93:1     skin:974:187|thyroid:618:71|blood:890:37|bowel:1782:35|lung:2761:17|unk:357:11|softtissue:739:11|testis:217:9|bladder:958:8|cnsbrain:2270:6|ovaryfallopiantube:699:5|biliarytract:358:5|uterus:618:5|headandneck:988:3|thymus:162:3|esophagusstomach:1407:3|pancreas:1059:2|bone:297:1|liver:636:1|kidney:1304:1|adrenalgland:291:1    TTG|ACA|CTT|TCG|CCC|CCA 0.0120300464273379      0.0267810594223141    24592   "pancan,skin,thyroid,bowel,blood,lung,softtissue,testis,bladder,cnsbrain,biliarytract,ovaryfallopiantube,uterus,thymus,headandneck,esophagusstomach"    0       NRAS 61       0       FALSE           NA      1       1.16795714944678        1.26187131041539        1.29838371117394        TRUE            165     257     RETAIN  TRUE    TRUE    Q       0    skin     skin:12|blood:7|bowel:2|lung:2|testis:2|softtissue:1|unk:1

Indel

Hugo_Symbol     Amino_Acid_Position     log10_pvalue    Mutation_Count  Reference_Amino_Acid    Total_Mutations_in_Gene Median_Allele_Freq_Rank Allele_Freq_Rank        SNP_ID  Variant_Amino_Acid    Codon_Change    Genomic_Position        Detailed_Cancer_Types   Organ_Types     Tri-nucleotides Mutability      mu_protein      ccf     Total_Samples   indel_size      qvalue  tm   Is_repeat        seq     length  align100        pad12entropy    pad24entropy    pad36entropy    TP      reason  n_MSK   n_Retro judgement       inNBT   inOncokb        Samples
SMARCA4 546     -7.75235638169585       5       QK:5    101     NA      NA      :NA     K546del:5       cAGAag/cag:5    19:11106926_5   lgg:536:4|dlbcl:246:1   cnsbrain:2283:4|lymph:366:1  NA       0.0573226243518208      0.0473351872460284      NA      24592   1       0.000230672905611517    SMARCA4 546     FALSE   NA      NA      1       0.91489630957268        1.2950060272429       1.33965330506364        FALSE   LOCAL_ENTROPY   1       4       RETAIN  FALSE   FALSE   cnsbrain:4|lymph:1
CDKN2A  27-42   -6.82111516846557       12      VRALLEA:4|LEAGALP:3|ALPN:1|EV:1|GA:1|PNAPN:1|RALLEA:1   219     NA      NA      :NA     V28_E33del:4    gTGCGGGCGCTGCTGGAGGcg/gcg:4|cTGGAGGCGGGGGCGCTGCcc/ccc:3|GGGGCG/-:1|gCGCTGCCCAac/gac:1|gAGGtg/gtg:1|CGGGCGCTGCTGGAGGCG/-:1|ccCAACGCACCGAAt/cct:1       9:21974727_4|9:21974715_3|9:21974745_1|9:21974725_1|9:21974719_1|9:21974712_1|9:21974702_1    luad:2071:3|esca:556:2|blca:852:1|skcm:192:1|icemu:1:1|paad:932:1|mel:595:1|stad:748:1|hnsc:650:1       esophagusstomach:1413:3|lung:2767:3|skin:974:2|bladder:955:1|cervix:234:1|pancreas:1059:1|headandneck:988:1   NA      0.0573226243518208      0.0473351872460284      NA      24592   15      8.77193090544841e-05    CDKN2A 27-42    FALSE   NA      NA      1    0.857780912379927        1.13008762297022        1.1577633500238 FALSE   LOCAL_ENTROPY   6       6       RETAIN  FALSE   FALSE   cervix:1|esophagusstomach:1|lung:1|pancreas:1
CDKN2A  27-42   -6.82111516846557       12      VRALLEA:4|LEAGALP:3|ALPN:1|EV:1|GA:1|PNAPN:1|RALLEA:1   219     NA      NA      :NA     L32_L37del:3    gTGCGGGCGCTGCTGGAGGcg/gcg:4|cTGGAGGCGGGGGCGCTGCcc/ccc:3|GGGGCG/-:1|gCGCTGCCCAac/gac:1|gAGGtg/gtg:1|CGGGCGCTGCTGGAGGCG/-:1|ccCAACGCACCGAAt/cct:1       9:21974727_4|9:21974715_3|9:21974745_1|9:21974725_1|9:21974719_1|9:21974712_1|9:21974702_1    luad:2071:3|esca:556:2|blca:852:1|skcm:192:1|icemu:1:1|paad:932:1|mel:595:1|stad:748:1|hnsc:650:1       esophagusstomach:1413:3|lung:2767:3|skin:974:2|bladder:955:1|cervix:234:1|pancreas:1059:1|headandneck:988:1   NA      0.0573226243518208      0.0473351872460284      NA      24592   15      8.77193090544841e-05    CDKN2A 27-42    FALSE   NA      NA      1    0.857780912379927        1.13008762297022        1.1577633500238 FALSE   LOCAL_ENTROPY   6       6       RETAIN  FALSE   FALSE   skin:2|esophagusstomach:1
CDKN2A  27-42   -6.82111516846557       12      VRALLEA:4|LEAGALP:3|ALPN:1|EV:1|GA:1|PNAPN:1|RALLEA:1   219     NA      NA      :NA     A36_N39delinsD:1        gTGCGGGCGCTGCTGGAGGcg/gcg:4|cTGGAGGCGGGGGCGCTGCcc/ccc:3|GGGGCG/-:1|gCGCTGCCCAac/gac:1|gAGGtg/gtg:1|CGGGCGCTGCTGGAGGCG/-:1|ccCAACGCACCGAAt/cct:1       9:21974727_4|9:21974715_3|9:21974745_1|9:21974725_1|9:21974719_1|9:21974712_1|9:21974702_1    luad:2071:3|esca:556:2|blca:852:1|skcm:192:1|icemu:1:1|paad:932:1|mel:595:1|stad:748:1|hnsc:650:1       esophagusstomach:1413:3|lung:2767:3|skin:974:2|bladder:955:1|cervix:234:1|pancreas:1059:1|headandneck:988:1   NA      0.0573226243518208      0.0473351872460284      NA      24592   15      8.77193090544841e-05    CDKN2A 27-42    FALSE   NA      NA   0.857780912379927        1.13008762297022        1.1577633500238 FALSE   LOCAL_ENTROPY   6       6       RETAIN  FALSE   FALSE   lung:1

Parsing

From the file, we're mainly interested in the following columns:

• Hugo_Symbol
• Amino_Acid_Position
• Mutation_Count
• Reference_Amino_Acid
• Variant_Amino_Acid
• qvalue

We map the gene symbol onto the canonical transcripts (RefSeq & Ensembl) for that gene. For SNVs, we obtain position, ref and alt amino acid from source file and generate substitution notation. For indels, we get protein change notation from Variant_Amino_Acid column and ref amino acids are ignored for indels. Then we match each entry using these notations.

We currently skip all variants labeled as splice from the source

Matching Strategy

Cancer Hotspots matching uses a tiered approach with three match types:

Allele-Specific (Exact Match)

The variant's HGVS protein notation is compared directly against the database entries. For SNVs, this means the gene symbol, amino acid position, reference amino acid, and alternate amino acid must all match. For indels, the protein change notation (e.g. V28_E33del) must match exactly. This is the highest-priority match.

Positional Match (SNVs only)

When an exact match is not found for an SNV, the annotator falls back to a position-based lookup. If the gene symbol and amino acid position match a known hotspot, the entry with the highest numSamples at that position is returned. Since the alternate amino acid differs from the database entry, numAltAminoAcidSamples is set to 0 in the output.

Interval Match (Indels only)

When an exact match is not found for an indel, the annotator checks whether the variant's affected amino acid range overlaps with any hotspot interval for the same gene. For example, a variant affecting positions 30-31 would match a hotspot interval of 27-42. The entry with the highest numSamples among overlapping intervals is returned, and numAltAminoAcidSamples is set to 0.

Match Priority

Allele-specific matches always take priority. Positional and interval fallbacks only apply when no exact match is found. For indels, interval matching is attempted before positional matching.

JSON Output

The data source will be captured under the cancerHotspots key in the transcript section.

Allele-Specific Match Example

{
   "transcript":"NM_002524.5",
   "source":"RefSeq",
   "bioType":"mRNA",
   "aminoAcids":"Q/K",
   "proteinPos":"61",
   "geneId":"4893",
   "hgnc":"NRAS",
   "hgvsc":"NM_002524.5:c.181C>A",
   "hgvsp":"NP_002515.1:p.(Gln61Lys)",
   "isCanonical":true,
   "proteinId":"NP_002515.1",
   "cancerHotspots":{
      "residue":"Q61",
      "numSamples":422,
      "numAltAminoAcidSamples":142,
      "qValue":0,
      "matchType":"alleleSpecific"
   }
}

Positional Match Example

When the exact alternate amino acid is not in the database but the position is a known hotspot:

{
   "transcript":"ENST00000369535.5",
   "source":"Ensembl",
   "bioType":"mRNA",
   "aminoAcids":"Q/E",
   "proteinPos":"61",
   "geneId":"4893",
   "hgnc":"NRAS",
   "hgvsc":"ENST00000369535.5:c.181C>G",
   "hgvsp":"ENSP00000358548.4:p.(Gln61Glu)",
   "isCanonical":true,
   "proteinId":"ENSP00000358548.4",
   "cancerHotspots":{
      "residue":"Q61",
      "numSamples":422,
      "numAltAminoAcidSamples":0,
      "qValue":0,
      "matchType":"positional"
   }
}

Interval Match Example

When an indel overlaps with a known hotspot interval:

{
   "transcript":"ENST00000304494.10",
   "source":"Ensembl",
   "bioType":"mRNA",
   "aminoAcids":"GA/",
   "proteinPos":"30-31",
   "geneId":"1029",
   "hgnc":"CDKN2A",
   "hgvsc":"ENST00000304494.10:c.89_94del",
   "hgvsp":"ENSP00000307101.5:p.(Gly30_Ala31del)",
   "isCanonical":true,
   "proteinId":"ENSP00000307101.5",
   "cancerHotspots":{
      "residue":"27-42",
      "numSamples":12,
      "numAltAminoAcidSamples":0,
      "qValue":0.0001,
      "matchType":"interval"
   }
}

Field	Type	Notes
residue	string	the amino acid position or range from the database entry
numSamples	int	how many samples are associated with a variant at the same amino acid position
numAltAminoAcidSamples	int	how many samples are associated with a variant with the same position and alternate amino acid. Set to 0 for positional and interval matches
qValue	double	rounded to 4 decimal places. Very small values (e.g. 6.05e-7) will be reported as 0
matchType	string	one of alleleSpecific, positional, or interval