> For the complete documentation index, see [llms.txt](https://help.connected.illumina.com/llms.txt). Markdown versions of documentation pages are available by appending `.md` to page URLs; this page is available as [Markdown](https://help.connected.illumina.com/annotation/data-sources/cancer-hotspots.md). # 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. {% hint style="info" %} **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. {% endhint %} ### Data extraction Illumina Connected Annotations currently parses SNV and indel tabs from hotspots\_v2.xls file to extract the relevant content. #### Example **SNV** ```scss 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** ```scss 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. {% hint style="warning" %} We currently skip all variants labeled as splice from the source {% endhint %} ### 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. {% hint style="info" %} **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. {% endhint %} ### JSON Output The data source will be captured under the cancerHotspots key in the transcript section. #### Allele-Specific Match Example ```json { "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: ```json { "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: ```json { "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` | --- # Agent Instructions This documentation is published with GitBook. GitBook is the documentation platform designed so that both humans and AI agents can read, navigate, and reason over technical content effectively. Learn more at gitbook.com. ## Querying This Documentation If you need additional information that is not directly available in this page, you can query the documentation dynamically by asking a question. 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