Mutation Analysis (MutSig v1.5)
Colon/Rectal Adenocarcinoma (Primary solid tumor)
21 April 2013  |  analyses__2013_04_21
Maintainer Information
Citation Information
doi:10.7908/C11C1TT7
Maintained by Dan DiCara (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Colon/Rectal Adenocarcinoma (Primary solid tumor cohort) - 21 April 2013: Mutation Analysis (MutSig v1.5). Broad Institute of MIT and Harvard. doi:10.7908/C11C1TT7
Overview
Introduction

This report serves to describe the mutational landscape and properties of a given individual set, as well as rank genes and genesets according to mutational significance. MutSig v1.5 was used to generate the results found in this report.

  • Working with individual set: COADREAD-TP

  • Number of patients in set: 224

Input

The input for this pipeline is a set of individuals with the following files associated for each:

  1. An annotated .maf file describing the mutations called for the respective individual, and their properties.

  2. A .wig file that contains information about the coverage of the sample.

Summary

  • MAF used for this analysis:COADREAD-TP.final_analysis_set.maf

  • Significantly mutated genes (q ≤ 0.1): 227

  • Mutations seen in COSMIC: 739

  • Significantly mutated genes in COSMIC territory: 29

  • Genes with clustered mutations (≤ 3 aa apart): 1746

  • Significantly mutated genesets: 146

  • Significantly mutated genesets: (excluding sig. mutated genes):0

Mutation Preprocessing

  • Read 140 MAFs of type "Broad"

  • Read 88 MAFs of type "Baylor-SOLiD"

  • Total number of mutations in input MAFs: 91973

  • After removing 1369 invalidated mutations: 90604

  • After removing 1176 noncoding mutations: 89428

  • After collapsing adjacent/redundant mutations: 82149

Mutation Filtering

  • Number of mutations before filtering: 82149

  • After removing 855 mutations outside gene set: 81294

  • After removing 343 mutations outside category set: 80951

  • After removing 11 "impossible" mutations in

  • gene-patient-category bins of zero coverage: 79742

Results
Breakdown of Mutations by Type

Table 1.  Get Full Table Table representing breakdown of mutations by type.

type count
De_novo_Start_InFrame 20
De_novo_Start_OutOfFrame 156
Frame_Shift_Del 1289
Frame_Shift_Ins 810
In_Frame_Del 166
In_Frame_Ins 26
Missense_Mutation 54081
Nonsense_Mutation 5053
Nonstop_Mutation 36
Read-through 10
Silent 19116
Splice_Site 186
Translation_Start_Site 2
Total 80951
Breakdown of Mutation Rates by Category Type

Table 2.  Get Full Table A breakdown of mutation rates per category discovered for this individual set.

category n N rate rate_per_mb relative_rate
*CpG->T 20381 335477044 0.000061 61 6
*Cp(A/C/T)->mut 21021 2775898083 7.6e-06 7.6 0.75
A->mut 12112 3017613932 4e-06 4 0.4
*CpG->(G/A) 562 335477044 1.7e-06 1.7 0.17
indel+null 7447 6128989199 1.2e-06 1.2 0.12
double_null 304 6128989199 5e-08 0.05 0.0049
Total 61827 6128989199 1e-05 10 1
Target Coverage for Each Individual

The x axis represents the samples. The y axis represents the exons, one row per exon, and they are sorted by average coverage across samples. For exons with exactly the same average coverage, they are sorted next by the %GC of the exon. (The secondary sort is especially useful for the zero-coverage exons at the bottom).

Figure 1. 

Distribution of Mutation Counts, Coverage, and Mutation Rates Across Samples

Figure 2.  Patients counts and rates file used to generate this plot: COADREAD-TP.patients.counts_and_rates.txt

CoMut Plot

Figure 3.  Get High-res Image The matrix in the center of the figure represents individual mutations in patient samples, color-coded by type of mutation, for the significantly mutated genes. The rate of synonymous and non-synonymous mutations is displayed at the top of the matrix. The barplot on the left of the matrix shows the number of mutations in each gene. The percentages represent the fraction of tumors with at least one mutation in the specified gene. The barplot to the right of the matrix displays the q-values for the most significantly mutated genes. The purple boxplots below the matrix (only displayed if required columns are present in the provided MAF) represent the distributions of allelic fractions observed in each sample. The plot at the bottom represents the base substitution distribution of individual samples, using the same categories that were used to calculate significance.

Significantly Mutated Genes

Column Descriptions:

  • N = number of sequenced bases in this gene across the individual set

  • n = number of (nonsilent) mutations in this gene across the individual set

  • npat = number of patients (individuals) with at least one nonsilent mutation

  • nsite = number of unique sites having a non-silent mutation

  • nsil = number of silent mutations in this gene across the individual set

  • n1 = number of nonsilent mutations of type: *CpG->T

  • n2 = number of nonsilent mutations of type: *Cp(A/C/T)->mut

  • n3 = number of nonsilent mutations of type: A->mut

  • n4 = number of nonsilent mutations of type: *CpG->(G/A)

  • n5 = number of nonsilent mutations of type: indel+null

  • n6 = number of nonsilent mutations of type: double_null

  • p = p-value (overall)

  • q = q-value, False Discovery Rate (Benjamini-Hochberg procedure)

Table 3.  Get Full Table A Ranked List of Significantly Mutated Genes. Number of significant genes found: 227. Number of genes displayed: 35. Click on a gene name to display its stick figure depicting the distribution of mutations and mutation types across the chosen gene (this feature may not be available for all significant genes).

rank gene description N n npat nsite nsil n1 n2 n3 n4 n5 n6 p q
1 TP53 tumor protein p53 267736 122 120 69 2 48 22 12 2 38 0 <1.00e-15 <1.69e-11
2 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 158010 96 96 11 0 0 91 4 0 1 0 2.11e-15 1.69e-11
3 FAM123B family with sequence similarity 123B 641973 27 25 24 2 1 3 4 0 19 0 3.66e-15 1.69e-11
4 APC adenomatous polyposis coli 1891000 187 160 128 4 6 15 11 0 103 52 3.77e-15 1.69e-11
5 FBXW7 F-box and WD repeat domain containing 7 577918 45 38 28 2 23 6 5 2 9 0 5.88e-15 1.79e-11
6 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 618889 40 33 21 2 6 20 14 0 0 0 6.99e-15 1.79e-11
7 SMAD4 SMAD family member 4 377497 29 26 22 0 10 6 9 0 3 1 7.55e-15 1.79e-11
8 NRAS neuroblastoma RAS viral (v-ras) oncogene homolog 131263 20 20 8 0 2 14 4 0 0 0 7.99e-15 1.79e-11
9 TTN titin 16863591 290 85 286 79 82 114 72 2 13 7 2.11e-13 4.20e-10
10 BRAF v-raf murine sarcoma viral oncogene homolog B1 493213 23 22 4 0 0 0 23 0 0 0 8.54e-12 1.53e-08
11 SMAD2 SMAD family member 2 322425 16 15 12 1 3 5 3 0 5 0 4.63e-11 7.55e-08
12 TCF7L2 transcription factor 7-like 2 (T-cell specific, HMG-box) 400503 20 18 18 4 5 5 3 0 7 0 9.40e-11 1.41e-07
13 PCDH9 protocadherin 9 823363 26 22 26 7 3 11 11 0 1 0 4.66e-09 6.44e-06
14 LRP1B low density lipoprotein-related protein 1B (deleted in tumors) 3162768 75 39 73 18 11 34 22 0 5 3 5.27e-09 6.76e-06
15 WBSCR17 Williams-Beuren syndrome chromosome region 17 400400 19 19 18 3 10 5 1 0 3 0 1.30e-08 1.56e-05
16 FAT4 FAT tumor suppressor homolog 4 (Drosophila) 3144726 73 39 73 21 19 30 19 1 4 0 3.76e-08 4.22e-05
17 KLHL4 kelch-like 4 (Drosophila) 494271 16 16 16 3 6 8 2 0 0 0 4.58e-08 4.84e-05
18 PRDM9 PR domain containing 9 448274 19 16 19 4 6 7 4 0 1 1 1.41e-07 0.000141
19 ACVR1B activin A receptor, type IB 339499 15 14 15 0 4 7 2 0 2 0 1.57e-07 0.000148
20 CSMD1 CUB and Sushi multiple domains 1 1444240 45 26 44 19 9 21 9 1 3 2 2.45e-07 0.000220
21 LIFR leukemia inhibitory factor receptor alpha 744473 24 18 24 5 4 6 9 1 4 0 3.77e-07 0.000323
22 MAP2K4 mitogen-activated protein kinase kinase 4 246117 11 11 10 1 3 4 2 0 2 0 4.09e-07 0.000333
23 CCDC160 coiled-coil domain containing 160 85540 9 7 9 0 0 4 0 1 3 1 6.02e-07 0.000470
24 CNTN6 contactin 6 708576 22 17 22 3 5 13 2 0 2 0 6.93e-07 0.000519
25 NRXN1 neurexin 1 761168 24 20 24 11 10 7 4 1 2 0 1.12e-06 0.000801
26 SOX9 SRY (sex determining region Y)-box 9 (campomelic dysplasia, autosomal sex-reversal) 256689 10 10 10 0 0 0 1 0 8 1 1.21e-06 0.000812
27 CPXCR1 CPX chromosome region, candidate 1 186322 10 9 10 1 2 5 2 0 1 0 1.22e-06 0.000812
28 DMD dystrophin (muscular dystrophy, Duchenne and Becker types) 2565596 47 33 46 6 10 14 14 0 9 0 1.27e-06 0.000812
29 KIAA1804 532518 18 15 16 0 8 7 1 0 2 0 1.89e-06 0.00117
30 KRTAP5-5 keratin associated protein 5-5 119310 4 4 1 1 0 0 0 4 0 0 2.66e-06 0.00159
31 SLITRK1 SLIT and NTRK-like family, member 1 448459 17 15 16 5 6 2 6 0 3 0 2.95e-06 0.00166
32 ZFHX4 zinc finger homeobox 4 1373120 43 24 42 18 11 22 7 0 3 0 2.96e-06 0.00166
33 ARID1A AT rich interactive domain 1A (SWI-like) 1266553 22 21 20 3 2 5 1 1 13 0 3.70e-06 0.00201
34 EPHA3 EPH receptor A3 678203 17 16 17 5 5 6 5 1 0 0 3.83e-06 0.00202
35 CTNNB1 catenin (cadherin-associated protein), beta 1, 88kDa 528618 12 11 12 0 3 4 3 1 1 0 3.98e-06 0.00204
COSMIC analyses

In this analysis, COSMIC is used as a filter to increase power by restricting the territory of each gene. Cosmic version: v48.

Table 4.  Get Full Table Significantly mutated genes (COSMIC territory only). To access the database please go to: COSMIC. Number of significant genes found: 29. Number of genes displayed: 10

rank gene description n cos n_cos N_cos cos_ev p q
1 APC adenomatous polyposis coli 187 839 137 187936 2584 0 0
2 TP53 tumor protein p53 122 824 122 184576 45406 0 0
3 ERBB3 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) 14 6 6 1344 6 7.9e-14 1.2e-10
4 NRAS neuroblastoma RAS viral (v-ras) oncogene homolog 20 33 18 7392 17998 3.7e-13 4.1e-10
5 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 96 52 95 11648 1013913 5.5e-13 5e-10
6 BRAF v-raf murine sarcoma viral oncogene homolog B1 23 89 20 19936 287480 8.7e-13 5.7e-10
7 FBXW7 F-box and WD repeat domain containing 7 45 91 31 20384 1228 8.9e-13 5.7e-10
8 KRTAP5-5 keratin associated protein 5-5 4 1 4 224 4 1.1e-12 6e-10
9 SMAD4 SMAD family member 4 29 159 19 35616 90 1.3e-12 6.7e-10
10 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 40 220 34 49280 13256 1.6e-12 7.2e-10

Note:

n - number of (nonsilent) mutations in this gene across the individual set.

cos = number of unique mutated sites in this gene in COSMIC

n_cos = overlap between n and cos.

N_cos = number of individuals times cos.

cos_ev = total evidence: number of reports in COSMIC for mutations seen in this gene.

p = p-value for seeing the observed amount of overlap in this gene)

q = q-value, False Discovery Rate (Benjamini-Hochberg procedure)

Clustered Mutations

Table 5.  Get Full Table Genes with Clustered Mutations

num gene desc n mindist nmuts0 nmuts3 nmuts12 npairs0 npairs3 npairs12
6654 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 96 0 2294 2964 3043 2294 2964 3043
13035 TP53 tumor protein p53 122 0 280 459 747 280 459 747
1255 BRAF v-raf murine sarcoma viral oncogene homolog B1 23 0 190 190 190 190 190 190
645 APC adenomatous polyposis coli 187 0 166 221 326 166 221 326
4535 FBXW7 F-box and WD repeat domain containing 7 45 0 81 87 105 81 87 105
9463 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 40 0 74 111 136 74 111 136
8399 NRAS neuroblastoma RAS viral (v-ras) oncogene homolog 20 0 61 73 73 61 73 73
11751 SMAD4 SMAD family member 4 29 0 24 30 56 24 30 56
4110 ERBB3 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) 14 0 10 15 15 10 15 15
4362 FAM22F family with sequence similarity 22, member F 9 0 10 10 10 10 10 10

Note:

n - number of mutations in this gene in the individual set.

mindist - distance (in aa) between closest pair of mutations in this gene

npairs3 - how many pairs of mutations are within 3 aa of each other.

npairs12 - how many pairs of mutations are within 12 aa of each other.

Geneset Analyses

Table 6.  Get Full Table A Ranked List of Significantly Mutated Genesets. (Source: MSigDB GSEA Cannonical Pathway Set).Number of significant genesets found: 146. Number of genesets displayed: 10

rank geneset description genes N_genes mut_tally N n npat nsite nsil n1 n2 n3 n4 n5 n6 p q
1 HSA04310_WNT_SIGNALING_PATHWAY Genes involved in Wnt signaling pathway APC, APC2, AXIN1, AXIN2, BTRC, CACYBP, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CCND1, CCND2, CCND3, CER1, CHD8, CHP, CREBBP, CSNK1A1, CSNK1A1L, CSNK1E, CSNK2A1, CSNK2A2, CSNK2B, CTBP1, CTBP2, CTNNB1, CTNNBIP1, CUL1, CXXC4, DAAM1, DAAM2, DKK1, DKK2, DKK4, DVL1, DVL2, DVL3, EP300, FBXW11, FOSL1, FRAT1, FRAT2, FZD1, FZD10, FZD2, FZD3, FZD4, FZD5, FZD6, FZD7, FZD8, FZD9, GSK3B, JUN, LEF1, LOC652788, LRP5, LRP6, MAP3K7, MAPK10, MAPK8, MAPK9, MMP7, MYC, NFAT5, NFATC1, NFATC2, NFATC3, NFATC4, NKD1, NKD2, NLK, PLCB1, PLCB2, PLCB3, PLCB4, PORCN, PPARD, PPP2CA, PPP2CB, PPP2R1A, PPP2R1B, PPP2R2A, PPP2R2B, PPP2R2C, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRICKLE1, PRICKLE2, PRKACA, PRKACB, PRKACG, PRKCA, PRKCB1, PRKCG, PRKX, PRKY, PSEN1, RAC1, RAC2, RAC3, RBX1, RHOA, ROCK1, ROCK2, RUVBL1, SENP2, SFRP1, SFRP2, SFRP4, SFRP5, SIAH1, SKP1, SMAD2, SMAD3, SMAD4, SOX17, TBL1X, TBL1XR1, TBL1Y, TCF7, TCF7L1, TCF7L2, TP53, VANGL1, VANGL2, WIF1, WNT1, WNT10A, WNT10B, WNT11, WNT16, WNT2, WNT2B, WNT3, WNT3A, WNT4, WNT5A, WNT5B, WNT6, WNT7A, WNT7B, WNT8A, WNT8B, WNT9A, WNT9B 144 APC(187), APC2(1), AXIN1(2), AXIN2(9), BTRC(5), CACYBP(2), CAMK2A(1), CAMK2B(2), CAMK2D(3), CAMK2G(2), CCND2(1), CCND3(1), CER1(3), CHD8(6), CREBBP(25), CSNK1A1(2), CSNK1A1L(5), CSNK2A1(4), CSNK2A2(2), CSNK2B(2), CTBP1(1), CTBP2(2), CTNNB1(12), CTNNBIP1(1), CUL1(8), CXXC4(1), DAAM1(2), DAAM2(9), DKK1(5), DKK2(6), DKK4(7), DVL2(9), DVL3(4), EP300(15), FBXW11(8), FZD1(1), FZD10(6), FZD2(2), FZD3(13), FZD4(2), FZD6(6), FZD7(3), FZD8(1), GSK3B(8), LEF1(4), LRP5(5), LRP6(17), MAP3K7(4), MAPK10(8), MAPK8(7), MAPK9(5), MMP7(5), NFAT5(5), NFATC1(2), NFATC2(5), NFATC3(5), NFATC4(5), NKD1(3), NKD2(1), NLK(1), PLCB1(8), PLCB2(3), PLCB3(4), PLCB4(10), PORCN(2), PPARD(2), PPP2CA(1), PPP2CB(2), PPP2R1A(4), PPP2R1B(2), PPP2R2A(1), PPP2R2B(3), PPP2R2C(4), PPP3CA(3), PPP3CB(5), PPP3CC(4), PPP3R1(1), PPP3R2(1), PRICKLE1(11), PRICKLE2(6), PRKACA(1), PRKACB(1), PRKACG(3), PRKCA(4), PRKCG(10), PRKX(2), PSEN1(3), RBX1(1), RHOA(5), ROCK1(15), ROCK2(6), RUVBL1(8), SENP2(3), SFRP1(3), SFRP2(3), SFRP4(4), SFRP5(1), SIAH1(1), SKP1(1), SMAD2(16), SMAD3(9), SMAD4(29), SOX17(2), TBL1X(6), TBL1XR1(6), TBL1Y(1), TCF7(6), TCF7L1(3), TCF7L2(20), TP53(122), VANGL1(2), VANGL2(5), WIF1(2), WNT1(1), WNT10B(4), WNT11(3), WNT16(2), WNT2(1), WNT2B(3), WNT3(4), WNT3A(1), WNT4(1), WNT5A(3), WNT6(1), WNT7A(2), WNT7B(2), WNT8A(2), WNT9A(2), WNT9B(2) 50774791 894 218 758 156 275 204 133 8 221 53 <1.00e-15 <4.11e-14
2 HSA04810_REGULATION_OF_ACTIN_CYTOSKELETON Genes involved in regulation of actin cytoskeleton ABI2, ACTN1, ACTN2, ACTN3, ACTN4, APC, APC2, ARAF, ARHGEF1, ARHGEF12, ARHGEF4, ARHGEF6, ARHGEF7, ARPC1A, ARPC1B, ARPC2, ARPC3, ARPC4, ARPC5, ARPC5L, BAIAP2, BCAR1, BDKRB1, BDKRB2, BRAF, C3orf10, CD14, CDC42, CFL1, CFL2, CHRM1, CHRM2, CHRM3, CHRM4, CHRM5, CRK, CRKL, CSK, CYFIP1, CYFIP2, DIAPH1, DIAPH2, DIAPH3, DOCK1, EGF, EGFR, EZR, F2, F2R, FGD1, FGD3, FGF1, FGF10, FGF11, FGF12, FGF13, FGF14, FGF16, FGF17, FGF18, FGF19, FGF2, FGF20, FGF21, FGF22, FGF23, FGF3, FGF4, FGF5, FGF6, FGF7, FGF8, FGF9, FGFR1, FGFR2, FGFR3, FGFR4, FN1, GIT1, GNA12, GNA13, GNG12, GRLF1, GSN, HRAS, INS, IQGAP1, IQGAP2, IQGAP3, ITGA1, ITGA10, ITGA11, ITGA2, ITGA2B, ITGA3, ITGA4, ITGA5, ITGA6, ITGA7, ITGA8, ITGA9, ITGAD, ITGAE, ITGAL, ITGAM, ITGAV, ITGAX, ITGB1, ITGB2, ITGB3, ITGB4, ITGB5, ITGB6, ITGB7, ITGB8, KRAS, LIMK1, LIMK2, LOC200025, LOC645126, LOC653888, MAP2K1, MAP2K2, MAPK1, MAPK3, MLCK, MOS, MRAS, MRCL3, MRLC2, MSN, MYH10, MYH14, MYH9, MYL2, MYL5, MYL7, MYL8P, MYL9, MYLC2PL, MYLK, MYLK2, MYLPF, NCKAP1, NCKAP1L, NRAS, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PDGFA, PDGFB, PDGFRA, PDGFRB, PFN1, PFN2, PFN3, PFN4, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PIP4K2A, PIP4K2B, PIP4K2C, PIP5K1A, PIP5K1B, PIP5K1C, PIP5K3, PPP1CA, PPP1CB, PPP1CC, PPP1R12A, PPP1R12B, PTK2, PXN, RAC1, RAC2, RAC3, RAF1, RDX, RHOA, ROCK1, ROCK2, RRAS, RRAS2, SCIN, SLC9A1, SOS1, SOS2, SSH1, SSH2, SSH3, TIAM1, TIAM2, TMSB4X, TMSB4Y, TMSL3, VAV1, VAV2, VAV3, VCL, WAS, WASF1, WASF2, WASL 203 ABI2(1), ACTN1(5), ACTN2(8), ACTN3(3), ACTN4(3), APC(187), APC2(1), ARAF(3), ARHGEF1(5), ARHGEF12(9), ARHGEF4(4), ARHGEF6(10), ARHGEF7(8), ARPC1A(5), ARPC1B(2), ARPC2(2), ARPC5(1), ARPC5L(2), BAIAP2(1), BDKRB2(3), BRAF(23), CD14(1), CDC42(1), CFL1(1), CHRM1(3), CHRM2(11), CHRM3(4), CHRM4(1), CHRM5(2), CRKL(2), CSK(3), CYFIP1(6), CYFIP2(5), DIAPH1(1), DIAPH2(12), DIAPH3(5), DOCK1(7), EGF(3), EGFR(11), EZR(2), F2(3), FGD1(8), FGD3(2), FGF1(2), FGF11(3), FGF12(3), FGF13(3), FGF14(5), FGF17(1), FGF19(1), FGF20(2), FGF21(1), FGF23(1), FGF3(1), FGF5(4), FGF6(3), FGF7(1), FGF8(1), FGF9(1), FGFR1(4), FGFR2(6), FGFR3(2), FGFR4(2), FN1(21), GIT1(3), GNA12(2), GNA13(2), GRLF1(12), IQGAP1(13), IQGAP2(12), IQGAP3(11), ITGA1(3), ITGA10(7), ITGA11(4), ITGA2(6), ITGA2B(4), ITGA3(4), ITGA4(8), ITGA5(7), ITGA6(4), ITGA7(6), ITGA8(8), ITGA9(6), ITGAD(8), ITGAE(7), ITGAL(8), ITGAM(8), ITGAV(5), ITGAX(6), ITGB1(6), ITGB2(5), ITGB3(9), ITGB4(3), ITGB5(6), ITGB6(6), ITGB7(4), ITGB8(5), KRAS(96), LIMK1(5), LIMK2(5), MAP2K1(4), MAP2K2(1), MAPK1(2), MAPK3(3), MOS(3), MRAS(1), MSN(6), MYH10(10), MYH14(12), MYH9(12), MYL2(1), MYL7(1), MYL9(2), MYLK(14), MYLK2(3), NCKAP1(9), NCKAP1L(11), NRAS(20), PAK1(5), PAK2(3), PAK3(5), PAK6(1), PAK7(7), PDGFA(1), PDGFRA(17), PDGFRB(6), PFN2(1), PFN4(1), PIK3CA(40), PIK3CB(2), PIK3CD(3), PIK3CG(14), PIK3R1(10), PIK3R2(1), PIK3R3(4), PIK3R5(1), PIP4K2A(2), PIP4K2B(2), PIP4K2C(3), PIP5K1A(3), PIP5K1B(2), PIP5K1C(4), PPP1CB(2), PPP1CC(2), PPP1R12A(3), PPP1R12B(9), PTK2(5), RAF1(6), RDX(3), RHOA(5), ROCK1(15), ROCK2(6), RRAS2(2), SCIN(3), SLC9A1(4), SOS1(7), SOS2(11), SSH1(6), SSH2(4), SSH3(1), TIAM1(17), TIAM2(16), TMSL3(1), VAV1(13), VAV2(4), VAV3(12), VCL(2), WAS(1), WASF1(3), WASF2(2), WASL(7) 87387370 1187 216 982 278 334 392 203 8 194 56 <1.00e-15 <4.11e-14
3 ST_ADRENERGIC Adrenergic receptors respond to epinephrine and norepinephrine signaling. AKT1, APC, AR, ASAH1, BF, BRAF, CAMP, CCL13, CCL15, CCL16, DAG1, EGFR, GAS, GNA11, GNA15, GNAI1, GNAQ, ITPKA, ITPKB, ITPR1, ITPR2, ITPR3, KCNJ3, KCNJ5, KCNJ9, MAPK1, MAPK10, MAPK14, PHKA2, PIK3CA, PIK3CD, PIK3R1, PITX2, PTX1, PTX3, RAF1, SRC 34 AKT1(2), APC(187), AR(6), ASAH1(3), BRAF(23), CCL13(1), CCL15(1), DAG1(5), EGFR(11), GNA11(1), GNA15(3), GNAI1(4), GNAQ(4), ITPKB(4), ITPR1(19), ITPR2(18), ITPR3(12), KCNJ3(6), KCNJ5(4), KCNJ9(3), MAPK1(2), MAPK10(8), MAPK14(3), PHKA2(6), PIK3CA(40), PIK3CD(3), PIK3R1(10), PITX2(2), PTX3(2), RAF1(6), SRC(3) 16590615 402 191 303 61 77 74 76 0 120 55 <1.00e-15 <4.11e-14
4 ST_WNT_BETA_CATENIN_PATHWAY Beta-catenin is degraded in the absence of Wnt signaling; when extracellular Wnt binds Frizzled receptors, beta-catenin accumulates in the nucleus and may promote cell survival. AKT1, AKT2, AKT3, ANKRD6, APC, AXIN1, AXIN2, C22orf2, CER1, CSNK1A1, CTNNB1, DACT1, DKK1, DKK2, DKK3, DKK4, DVL1, FRAT1, FSTL1, GSK3A, GSK3B, IDAX, LAMR1, LRP1, MVP, NKD1, NKD2, PIN1, PSEN1, PTPRA, SENP2, SFRP1, TSHB, WIF1 30 AKT1(2), AKT2(6), AKT3(1), ANKRD6(5), APC(187), AXIN1(2), AXIN2(9), CER1(3), CSNK1A1(2), CTNNB1(12), DACT1(6), DKK1(5), DKK2(6), DKK3(2), DKK4(7), FSTL1(6), GSK3A(2), GSK3B(8), LRP1(17), MVP(4), NKD1(3), NKD2(1), PIN1(1), PSEN1(3), PTPRA(2), SENP2(3), SFRP1(3), TSHB(1), WIF1(2) 12642186 311 185 249 37 60 43 39 1 116 52 <1.00e-15 <4.11e-14
5 GSK3PATHWAY Bacterial lipopolysaccharide activates AKT to promote the survival and activation of macrophages and inhibits Gsk3-beta to promote beta-catenin accumulation in the nucleus. AKT1, APC, AXIN1, CCND1, CD14, CTNNB1, DVL1, FZD1, GJA1, GNAI1, GSK3B, IRAK1, LBP, LEF1, LY96, MYD88, NFKB1, PDPK1, PIK3CA, PIK3R1, PPP2CA, PRKR, RELA, TIRAP, TLR4, TOLLIP, WNT1 26 AKT1(2), APC(187), AXIN1(2), CD14(1), CTNNB1(12), FZD1(1), GJA1(7), GNAI1(4), GSK3B(8), IRAK1(1), LBP(1), LEF1(4), LY96(2), MYD88(2), NFKB1(6), PDPK1(1), PIK3CA(40), PIK3R1(10), PPP2CA(1), RELA(2), TIRAP(1), TLR4(10), TOLLIP(1), WNT1(1) 9451888 307 183 228 28 44 50 43 1 115 54 <1.00e-15 <4.11e-14
6 PITX2PATHWAY The bicoid-related transcription factor Pitx2 is activated by Wnt binding to the Frizzled receptor and induces tissue-specific cell proliferation. APC, AXIN1, CREBBP, CTNNB1, DVL1, EP300, FZD1, GSK3B, HDAC1, HTATIP, LDB1, LEF1, PITX2, PPARBP, TRRAP, WNT1 14 APC(187), AXIN1(2), CREBBP(25), CTNNB1(12), EP300(15), FZD1(1), GSK3B(8), HDAC1(2), LDB1(5), LEF1(4), PITX2(2), TRRAP(21), WNT1(1) 10494881 285 180 225 29 46 36 32 2 117 52 <1.00e-15 <4.11e-14
7 CELL_CYCLE_KEGG ABL1, ASK, ATM, BUB1, BUB1B, BUB3, CCNA1, CCNA2, CCNB1, CCNB2, CCNB3, CCND2, CCND3, CCNE1, CCNE2, CCNH, CDAN1, CDC14A, CDC14B, CDC14B, CDC14C, CDC2, CDC20, CDC25A, CDC25B, CDC25C, CDC45L, CDC6, CDC7, CDH1, CDK2, CDK4, CDKN1A, CDKN2A, CHEK1, CHEK2, DTX4, E2F1, E2F2, E2F3, E2F4, E2F5, E2F6, EP300, ESPL1, FLJ14001, GADD45A, GSK3B, HDAC1, HDAC2, HDAC3, HDAC4, HDAC5, HDAC6, HDAC7A, HDAC8, MAD1L1, MAD2L1, MAD2L2, MCM2, MCM3, MCM4, MCM5, MCM6, MCM7, MDM2, MPEG1, MPL, ORC1L, ORC2L, ORC3L, ORC4L, ORC5L, ORC6L, PCNA, PLK1, PRKDC, PTPRA, PTTG1, PTTG2, PTTG3, RB1, RBL1, SKP2, SMAD4, SMC1L1, TBC1D8, TFDP1, TGFB1, TP53, WEE1 82 ABL1(4), ATM(37), BUB1(6), BUB1B(6), BUB3(2), CCNA1(6), CCNA2(3), CCNB1(2), CCNB2(2), CCNB3(7), CCND2(1), CCND3(1), CCNE1(3), CCNE2(2), CCNH(2), CDAN1(3), CDC14A(4), CDC14B(4), CDC20(3), CDC25A(2), CDC25B(5), CDC25C(4), CDC6(1), CDC7(3), CDH1(5), CDK2(2), CDK4(3), CDKN1A(1), CDKN2A(1), CHEK1(1), CHEK2(1), DTX4(3), E2F2(1), E2F3(2), E2F4(1), E2F5(2), EP300(15), ESPL1(8), GSK3B(8), HDAC1(2), HDAC2(2), HDAC3(2), HDAC4(5), HDAC5(2), HDAC6(6), MAD1L1(2), MAD2L1(1), MAD2L2(1), MCM3(3), MCM4(4), MCM5(6), MCM6(4), MCM7(3), MDM2(4), MPEG1(4), MPL(2), ORC1L(1), ORC3L(1), ORC4L(1), ORC5L(1), PCNA(3), PLK1(8), PRKDC(18), PTPRA(2), PTTG1(1), RB1(7), RBL1(5), SKP2(1), SMAD4(29), TBC1D8(5), TFDP1(4), TGFB1(1), TP53(122), WEE1(3) 34828727 433 178 369 75 131 122 88 8 80 4 <1.00e-15 <4.11e-14
8 HSA04012_ERBB_SIGNALING_PATHWAY Genes involved in ErbB signaling pathway ABL1, ABL2, AKT1, AKT2, AKT3, ARAF, AREG, BAD, BRAF, BTC, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CBL, CBLB, CBLC, CDKN1A, CDKN1B, CRK, CRKL, EGF, EGFR, EIF4EBP1, ELK1, ERBB2, ERBB3, ERBB4, EREG, FRAP1, GAB1, GRB2, GSK3B, HBEGF, HRAS, JUN, KRAS, MAP2K1, MAP2K2, MAP2K4, MAP2K7, MAPK1, MAPK10, MAPK3, MAPK8, MAPK9, MYC, NCK1, NCK2, NRAS, NRG1, NRG2, NRG3, NRG4, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PLCG1, PLCG2, PRKCA, PRKCB1, PRKCG, PTK2, RAF1, RPS6KB1, RPS6KB2, SHC1, SHC2, SHC3, SHC4, SOS1, SOS2, SRC, STAT5A, STAT5B, TGFA 85 ABL1(4), ABL2(7), AKT1(2), AKT2(6), AKT3(1), ARAF(3), BAD(1), BRAF(23), BTC(2), CAMK2A(1), CAMK2B(2), CAMK2D(3), CAMK2G(2), CBL(5), CBLB(8), CDKN1A(1), CDKN1B(3), CRKL(2), EGF(3), EGFR(11), ERBB2(10), ERBB3(14), ERBB4(21), EREG(1), GAB1(6), GRB2(3), GSK3B(8), HBEGF(1), KRAS(96), MAP2K1(4), MAP2K2(1), MAP2K4(11), MAPK1(2), MAPK10(8), MAPK3(3), MAPK8(7), MAPK9(5), NCK1(1), NRAS(20), NRG1(15), NRG2(6), NRG3(7), NRG4(1), PAK1(5), PAK2(3), PAK3(5), PAK6(1), PAK7(7), PIK3CA(40), PIK3CB(2), PIK3CD(3), PIK3CG(14), PIK3R1(10), PIK3R2(1), PIK3R3(4), PIK3R5(1), PLCG1(4), PLCG2(13), PRKCA(4), PRKCG(10), PTK2(5), RAF1(6), RPS6KB1(3), RPS6KB2(2), SHC1(3), SHC2(1), SHC3(1), SHC4(5), SOS1(7), SOS2(11), SRC(3), STAT5B(3) 33296728 518 175 369 98 118 227 115 5 51 2 <1.00e-15 <4.11e-14
9 TGFBPATHWAY The TGF-beta receptor responds to ligand binding by activating the SMAD family of transcriptional regulations, commonly blocking cell growth. APC, CDH1, CREBBP, EP300, MADH2, MADH3, MADH4, MADH7, MADHIP, MAP2K1, MAP3K7, MAP3K7IP1, MAPK3, SKIL, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2 13 APC(187), CDH1(5), CREBBP(25), EP300(15), MAP2K1(4), MAP3K7(4), MAPK3(3), SKIL(1), TGFB1(1), TGFB2(9), TGFBR1(9), TGFBR2(7) 8403558 270 175 210 25 34 35 30 1 118 52 <1.00e-15 <4.11e-14
10 HSA04662_B_CELL_RECEPTOR_SIGNALING_PATHWAY Genes involved in B cell receptor signaling pathway AKT1, AKT2, AKT3, BCL10, BLNK, BTK, CARD11, CD19, CD22, CD72, CD79A, CD79B, CD81, CHP, CHUK, CR2, FCGR2B, FOS, GSK3B, HRAS, IFITM1, IKBKB, IKBKG, INPP5D, JUN, KRAS, LILRB3, LYN, MALT1, NFAT5, NFATC1, NFATC2, NFATC3, NFATC4, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NRAS, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PLCG2, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRKCB1, PTPN6, RAC1, RAC2, RAC3, RASGRP3, SYK, VAV1, VAV2, VAV3 62 AKT1(2), AKT2(6), AKT3(1), BCL10(3), BLNK(1), BTK(7), CARD11(9), CD19(3), CD22(10), CD72(4), CD79A(3), CD79B(1), CHUK(6), CR2(11), FOS(1), GSK3B(8), IFITM1(1), IKBKB(4), INPP5D(4), KRAS(96), LILRB3(2), LYN(4), MALT1(7), NFAT5(5), NFATC1(2), NFATC2(5), NFATC3(5), NFATC4(5), NFKB1(6), NFKB2(4), NFKBIB(1), NFKBIE(2), NRAS(20), PIK3CA(40), PIK3CB(2), PIK3CD(3), PIK3CG(14), PIK3R1(10), PIK3R2(1), PIK3R3(4), PIK3R5(1), PLCG2(13), PPP3CA(3), PPP3CB(5), PPP3CC(4), PPP3R1(1), PPP3R2(1), PTPN6(4), RASGRP3(7), SYK(3), VAV1(13), VAV2(4), VAV3(12) 23448894 394 157 272 64 111 195 57 1 28 2 <1.00e-15 <4.11e-14

Table 7.  Get Full Table A Ranked List of Significantly Mutated Genesets (Excluding Significantly Mutated Genes). Number of significant genesets found: 0. Number of genesets displayed: 10

rank geneset description genes N_genes mut_tally N n npat nsite nsil n1 n2 n3 n4 n5 n6 p q
1 CREMPATHWAY The transcription factor CREM activates a post-meiotic transcriptional cascade culminating in spermatogenesis. ADCY1, CREM, FHL5, FSHB, FSHR, GNAS, XPO1 7 ADCY1(8), CREM(4), FHL5(4), FSHB(2), FSHR(7), GNAS(6), XPO1(2) 3039066 33 29 33 12 13 9 7 1 3 0 0.0016 0.99
2 ALTERNATIVEPATHWAY The alternative complement pathway is an antibody-independent mechanism of immune activation that results in cell lysis via the membrane attack complex. BF, C3, C5, C6, C7, C8A, C9, DF, PFC 6 C3(11), C5(13), C6(13), C7(5), C8A(6), C9(5) 4019457 53 30 53 14 16 19 10 0 7 1 0.0059 1
3 ERBB3PATHWAY Neuregulins bind to the receptor tyrosine kinases ErbB3 and ErbB4, surface-localized receptors whose overexpression induces tumor formation. EGF, EGFR, ERBB3, NRG1, UBE2D1 5 EGF(3), EGFR(11), ERBB3(14), NRG1(15), UBE2D1(1) 3378947 44 33 40 7 18 8 11 1 6 0 0.0071 1
4 EOSINOPHILSPATHWAY Recruitment of eosinophils in the inflammatory response observed in asthma occurs via the chemoattractant eotaxin binding to the CCR3 receptor. CCL11, CCL5, CCR3, CSF2, HLA-DRA, HLA-DRB1, IL3, IL5 8 CCR3(4), HLA-DRA(5), HLA-DRB1(2), IL3(3) 949081 14 12 13 4 7 5 0 0 0 2 0.011 1
5 FLUMAZENILPATHWAY Flumazenil is a benzodiazepine receptor antagonist that may induce protective preconditioning in ischemic cardiomyocytes. GABRA1, GABRA2, GABRA3, GABRA4, GABRA5, GABRA6, GPX1, PRKCE, SOD1 8 GABRA1(4), GABRA2(9), GABRA3(5), GABRA4(8), GABRA6(5), GPX1(1), PRKCE(6) 2175145 38 22 37 6 11 17 6 0 4 0 0.012 1
6 1_AND_2_METHYLNAPHTHALENE_DEGRADATION ADH1A, ADH1A, ADH1B, ADH1C, ADH1B, ADH1C, ADH4, ADH6, ADH7, ADHFE1 7 ADH1A(1), ADH1B(3), ADH1C(4), ADH4(2), ADH6(6), ADH7(2), ADHFE1(6) 1762715 24 19 24 9 3 9 11 0 1 0 0.014 1
7 CCR3PATHWAY CCR3 is a G-protein coupled receptor that recruits eosinophils to inflammation sites via chemokine ligands. ARHA, CCL11, CCR3, CFL1, GNAQ, GNAS, GNB1, GNGT1, HRAS, LIMK1, MAP2K1, MAPK1, MAPK3, MYL2, NOX1, PIK3C2G, PLCB1, PPP1R12B, PRKCA, PRKCB1, PTK2, RAF1, ROCK2 21 CCR3(4), CFL1(1), GNAQ(4), GNAS(6), GNB1(1), GNGT1(1), LIMK1(5), MAP2K1(4), MAPK1(2), MAPK3(3), MYL2(1), NOX1(1), PIK3C2G(9), PLCB1(8), PPP1R12B(9), PRKCA(4), PTK2(5), RAF1(6), ROCK2(6) 7894259 80 47 78 16 30 21 13 1 15 0 0.015 1
8 ACETYLCHOLINE_SYNTHESIS ACHE, CHAT, CHKA, PCYT1A, PDHA1, PDHA2, PEMT, SLC18A3 8 ACHE(2), CHAT(6), CHKA(4), PCYT1A(5), PDHA1(5), PDHA2(8), PEMT(1), SLC18A3(6) 2214030 37 26 36 17 12 12 10 0 3 0 0.016 1
9 COMPLEMENT_ACTIVATION_CLASSICAL C1QA, C1QB, C1QG, C1R, C1S, C2, C3, C4A, C4B, C5, C6, C7, C8A, C8B, C9, DAF, MASP1 12 C1QB(1), C1R(3), C1S(6), C2(4), C3(11), C5(13), C6(13), C7(5), C8A(6), C9(5), MASP1(12) 6230922 79 39 79 26 26 27 14 0 11 1 0.016 1
10 GPCRDB_CLASS_C_METABOTROPIC_GLUTAMATE_PHEROMONE CASR, GABBR1, GPCR5A, GPR51, GPRC5A, GPRC5B, GPRC5C, GPRC5D, GRM1, GRM2, GRM3, GRM4, GRM5, GRM7, GRM8 13 CASR(7), GABBR1(6), GPRC5A(2), GPRC5B(2), GPRC5C(2), GPRC5D(1), GRM1(12), GRM2(4), GRM3(7), GRM4(7), GRM5(11), GRM7(12), GRM8(9) 6585022 82 48 80 47 35 23 14 1 9 0 0.018 1
Methods & Data
Methods

In brief, we tabulate the number of mutations and the number of covered bases for each gene. The counts are broken down by mutation context category: four context categories that are discovered by MutSig, and one for indel and 'null' mutations, which include indels, nonsense mutations, splice-site mutations, and non-stop (read-through) mutations. For each gene, we calculate the probability of seeing the observed constellation of mutations, i.e. the product P1 x P2 x ... x Pm, or a more extreme one, given the background mutation rates calculated across the dataset. [1]

Download Results

This is an experimental feature. The full results of the analysis summarized in this report can be downloaded from the TCGA Data Coordination Center.

References
[1] TCGA, Integrated genomic analyses of ovarian carcinoma, Nature 474:609 - 615 (2011)
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