Mutation Analysis (MutSig v2.0 and MutSigCV v0.9 merged result)
Colon/Rectal Adenocarcinoma (Primary solid tumor)
23 May 2013  |  analyses__2013_05_23
Maintainer Information
Citation Information
doi:10.7908/C1V122TH
Maintained by Dan DiCara (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Mutation Analysis (MutSig v2.0 and MutSigCV v0.9 merged result). Broad Institute of MIT and Harvard. doi:10.7908/C1V122TH
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 v2.0 and MutSigCV v0.9 merged result 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): 20

  • Mutations seen in COSMIC: 739

  • Significantly mutated genes in COSMIC territory: 29

  • Significantly mutated genesets: 146

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_cons = p-value for enrichment of mutations at evolutionarily most-conserved sites in gene

  • p_joint = p-value for clustering + conservation

  • 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: 20. 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_cons p_joint p_cv p q
1 APC adenomatous polyposis coli 1891000 187 160 128 4 6 15 11 0 103 52 0.98 0 3.2e-15 0 0
2 FBXW7 F-box and WD repeat domain containing 7 577918 45 38 28 2 23 6 5 2 9 0 0.052 0.000048 4.1e-15 0 0
3 NRAS neuroblastoma RAS viral (v-ras) oncogene homolog 131263 20 20 8 0 2 14 4 0 0 0 0.16 0.000061 1.5e-14 0 0
4 BRAF v-raf murine sarcoma viral oncogene homolog B1 493213 23 22 4 0 0 0 23 0 0 0 0 0 5.5e-06 0 0
5 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 158010 96 96 11 0 0 91 4 0 1 0 0.0014 0 5.6e-15 0 0
6 TP53 tumor protein p53 267736 122 120 69 2 48 22 12 2 38 0 0 0 2.7e-15 0 0
7 SMAD4 SMAD family member 4 377497 29 26 22 0 10 6 9 0 3 1 0.0024 0.0022 5.9e-14 4.9e-15 1.3e-11
8 FAM123B family with sequence similarity 123B 641973 27 25 24 2 1 3 4 0 19 0 0.85 0.019 1.6e-12 9.7e-13 2.2e-09
9 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 618889 40 33 21 2 6 20 14 0 0 0 0.00015 2e-06 3.5e-08 2.2e-12 4.3e-09
10 SMAD2 SMAD family member 2 322425 16 15 12 1 3 5 3 0 5 0 0.18 0.02 1.2e-07 4.7e-08 0.000085
11 TCF7L2 transcription factor 7-like 2 (T-cell specific, HMG-box) 400503 20 18 18 4 5 5 3 0 7 0 0.21 0.022 2e-07 9.2e-08 0.00015
12 ACVR2A activin A receptor, type IIA 354442 10 9 9 1 0 0 4 0 5 1 0.011 0.018 5.5e-07 2e-07 0.00029
13 SOX9 SRY (sex determining region Y)-box 9 (campomelic dysplasia, autosomal sex-reversal) 256689 10 10 10 0 0 0 1 0 8 1 0.48 0.07 2.2e-07 2.9e-07 0.0004
14 ELF3 E74-like factor 3 (ets domain transcription factor, epithelial-specific ) 238851 6 6 5 0 0 0 1 0 5 0 0.34 0.015 2e-06 5.4e-07 0.0007
15 CRTC1 CREB regulated transcription coactivator 1 348788 6 6 3 1 1 0 0 0 5 0 0.059 0.0013 0.0004 7.9e-06 0.0095
16 TNFRSF10C tumor necrosis factor receptor superfamily, member 10c, decoy without an intracellular domain 167178 6 6 2 0 0 6 0 0 0 0 1 0.000071 0.012 0.000012 0.014
17 KRTAP5-5 keratin associated protein 5-5 119310 4 4 1 1 0 0 0 4 0 0 0.000048 0.000048 0.029 2e-05 0.021
18 KIAA1804 532518 18 15 16 0 8 7 1 0 2 0 0.017 0.0091 0.0002 0.000025 0.025
19 ACOT4 acyl-CoA thioesterase 4 215425 3 3 2 1 0 0 0 0 2 1 0.026 0.00041 0.015 0.000078 0.074
20 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 260038 10 7 8 1 3 2 1 0 3 1 0.0065 0.012 0.00067 0.0001 0.09
21 MYO1B myosin IB 774252 15 13 14 2 1 3 4 0 5 2 0.96 0.044 0.00025 0.00014 0.12
22 PCBP1 poly(rC) binding protein 1 176357 6 6 3 0 0 0 6 0 0 0 0.0035 0.0003 0.12 0.0004 0.32
23 GGT1 gamma-glutamyltransferase 1 245492 3 3 1 1 0 3 0 0 0 0 0.000053 0.000038 0.96 0.00041 0.32
24 CDC27 cell division cycle 27 homolog (S. cerevisiae) 510134 13 10 9 6 3 1 6 0 3 0 0.97 0.079 0.00052 0.00046 0.34
25 CCDC160 coiled-coil domain containing 160 85540 9 7 9 0 0 4 0 1 3 1 0.38 0.87 0.000048 0.00046 0.34
26 ACVR1B activin A receptor, type IB 339499 15 14 15 0 4 7 2 0 2 0 0.00093 0.0044 0.015 0.0007 0.48
27 DKK2 dickkopf homolog 2 (Xenopus laevis) 176618 6 6 5 1 6 0 0 0 0 0 0.13 0.00039 0.18 0.00076 0.5
28 FAM116A family with sequence similarity 116, member A 387395 6 6 6 0 2 1 1 0 2 0 0.071 0.0026 0.029 0.00077 0.5
29 SAT1 spermidine/spermine N1-acetyltransferase 1 111639 4 4 2 0 0 0 1 0 3 0 NaN NaN 0.0011 0.0011 0.7
30 B2M beta-2-microglobulin 82419 6 5 5 0 0 1 2 0 2 1 0.49 1 0.00011 0.0011 0.7
31 HTR3B 5-hydroxytryptamine (serotonin) receptor 3B 304904 6 6 5 1 4 2 0 0 0 0 0.00022 0.0013 0.09 0.0012 0.7
32 LOXL2 lysyl oxidase-like 2 481795 10 9 10 2 7 1 1 0 1 0 0.87 0.002 0.065 0.0013 0.72
33 ZNF593 zinc finger protein 593 41786 4 4 4 0 1 1 0 0 2 0 0.66 1 0.00022 0.0021 1
34 KLK2 kallikrein-related peptidase 2 182657 3 3 1 1 0 3 0 0 0 0 0.27 0.0005 0.54 0.0025 1
35 MGC26647 chromosome 7 open reading frame 62 169881 7 7 7 0 1 2 1 0 3 0 0.79 0.21 0.0013 0.0025 1
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)

Geneset Analyses

Table 5.  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
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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