Mutation Analysis (MutSig v1.5)
Thyroid Adenocarcinoma (Primary solid tumor)
01 July 2013  |  awg_thca__2013_07_01
Maintainer Information
Citation Information
doi:10.7908/C1H993CD
Maintained by Dan DiCara (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Mutation Analysis (MutSig v1.5). Broad Institute of MIT and Harvard. doi:10.7908/C1H993CD
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: THCA-TP

  • Number of patients in set: 401

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:THCA-TP.final_analysis_set.maf

  • Significantly mutated genes (q ≤ 0.1): 6

  • Mutations seen in COSMIC: 307

  • Significantly mutated genes in COSMIC territory: 9

  • Genes with clustered mutations (≤ 3 aa apart): 45

  • Significantly mutated genesets: 86

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

Mutation Preprocessing

  • Read 401 MAFs of type "Broad"

  • Total number of mutations in input MAFs: 7315

  • After removing 1 mutations outside chr1-24: 7314

  • After removing 2 blacklisted mutations: 7312

  • After removing 70 noncoding mutations: 7242

  • After collapsing adjacent/redundant mutations: 6877

Mutation Filtering

  • Number of mutations before filtering: 6877

  • After removing 250 mutations outside gene set: 6627

  • After removing 5 mutations outside category set: 6622

Results
Breakdown of Mutations by Type

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

type count
Frame_Shift_Del 185
Frame_Shift_Ins 33
In_Frame_Del 25
In_Frame_Ins 5
Missense_Mutation 4301
Nonsense_Mutation 232
Nonstop_Mutation 3
Silent 1634
Splice_Site 204
Total 6622
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 exp_ns_s_ratio
*CpG->T 799 651869559 1.2e-06 1.2 2.9 2.1
*Cp(A/C/T)->T 1006 5343235736 1.9e-07 0.19 0.44 1.7
A->G 806 5758342040 1.4e-07 0.14 0.33 2.3
transver 1690 11753447335 1.4e-07 0.14 0.34 5
indel+null 682 11753447335 5.8e-08 0.058 0.14 NaN
double_null 5 11753447335 4.3e-10 0.00043 0.001 NaN
Total 4988 11753447335 4.2e-07 0.42 1 3.5
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: THCA-TP.patients.counts_and_rates.txt

Needs description.

Figure 3.  Needs description.

Figure 4.  Needs description.

CoMut Plot

Figure 5.  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)->T

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

  • n4 = number of nonsilent mutations of type: transver

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

  • n6 = number of nonsilent mutations of type: double_null

  • p_ns_s = p-value for the observed nonsilent/silent ratio being elevated in this gene

  • 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: 6. 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_ns_s p q
1 BRAF v-raf murine sarcoma viral oncogene homolog B1 891806 233 233 2 2 0 0 1 232 0 0 <1.00e-15 <1.00e-15 <1.81e-11
2 NRAS neuroblastoma RAS viral (v-ras) oncogene homolog 234968 34 34 2 0 0 0 27 7 0 0 8.81e-06 2.44e-15 2.21e-11
3 HRAS v-Ha-ras Harvey rat sarcoma viral oncogene homolog 260068 14 14 2 0 0 0 11 3 0 0 0.0940 1.75e-14 1.06e-10
4 EIF1AX eukaryotic translation initiation factor 1A, X-linked 176670 6 6 5 0 0 3 0 1 1 1 0.235 1.06e-11 4.77e-08
5 CHEK2 CHK2 checkpoint homolog (S. pombe) 635246 5 5 5 0 0 0 1 3 1 0 0.333 5.16e-06 0.0187
6 S100A7 S100 calcium binding protein A7 125914 3 3 3 0 0 0 0 3 0 0 0.679 1.43e-05 0.0431
7 TMSB15A thymosin beta 15a 58475 2 2 2 0 0 1 0 1 0 0 0.592 5.02e-05 0.130
8 MSI1 musashi homolog 1 (Drosophila) 314086 3 3 3 0 1 0 0 1 1 0 0.502 0.000109 0.218
9 SLA Src-like-adaptor 331458 3 3 3 0 0 0 1 0 2 0 0.755 0.000117 0.218
10 NUP93 nucleoporin 93kDa 1019329 4 4 2 0 0 1 0 0 3 0 0.118 0.000120 0.218
11 ADO 2-aminoethanethiol (cysteamine) dioxygenase 142989 2 2 2 0 0 0 0 2 0 0 0.648 0.000139 0.218
12 EFCAB1 EF-hand calcium binding domain 1 258647 2 2 2 0 1 0 0 0 1 0 0.730 0.000167 0.218
13 PPM1D protein phosphatase 1D magnesium-dependent, delta isoform 625749 3 3 3 0 0 1 0 0 2 0 0.700 0.000171 0.218
14 SLC25A45 solute carrier family 25, member 45 357268 3 3 3 1 1 1 1 0 0 0 0.704 0.000188 0.218
15 BRIX1 BRX1, biogenesis of ribosomes, homolog (S. cerevisiae) 362678 3 3 3 0 0 1 1 1 0 0 0.410 0.000191 0.218
16 C11orf87 chromosome 11 open reading frame 87 235201 3 3 3 0 2 0 0 1 0 0 0.301 0.000203 0.218
17 SAMD1 sterile alpha motif domain containing 1 179155 2 2 2 0 1 0 1 0 0 0 0.451 0.000205 0.218
18 CDH8 cadherin 8, type 2 977850 4 4 4 1 1 0 0 3 0 0 0.658 0.000272 0.264
19 CD163 CD163 molecule 1404720 4 4 4 0 2 1 1 0 0 0 0.228 0.000292 0.264
20 DNAH9 dynein, axonemal, heavy chain 9 5321086 9 9 9 1 2 3 1 3 0 0 0.139 0.000292 0.264
21 RPRD1A regulation of nuclear pre-mRNA domain containing 1A 348090 3 3 3 0 1 0 0 1 1 0 0.491 0.000392 0.326
22 SPTA1 spectrin, alpha, erythrocytic 1 (elliptocytosis 2) 2989120 6 6 6 0 0 3 0 1 2 0 0.0708 0.000400 0.326
23 BAGE B melanoma antigen 50513 1 1 1 0 1 0 0 0 0 0 0.500 0.000414 0.326
24 COL5A3 collagen, type V, alpha 3 1951751 5 5 5 0 2 1 0 2 0 0 0.191 0.000497 0.367
25 PLP1 proteolipid protein 1 (Pelizaeus-Merzbacher disease, spastic paraplegia 2, uncomplicated) 345054 2 2 2 1 2 0 0 0 0 0 0.644 0.000508 0.367
26 DNASE2 deoxyribonuclease II, lysosomal 407482 3 3 3 0 0 2 1 0 0 0 0.269 0.000534 0.372
27 IL7R interleukin 7 receptor 565317 3 3 3 0 0 0 1 1 1 0 0.489 0.000585 0.392
28 MED31 mediator complex subunit 31 162831 2 2 2 0 0 0 0 1 1 0 0.587 0.000662 0.409
29 SNRNP70 small nuclear ribonucleoprotein 70kDa (U1) 278825 2 2 2 1 0 1 0 0 1 0 0.908 0.000675 0.409
30 TBC1D7 TBC1 domain family, member 7 363943 2 2 2 0 0 1 0 0 1 0 0.548 0.000678 0.409
31 OR5T2 olfactory receptor, family 5, subfamily T, member 2 431043 2 2 2 0 1 1 0 0 0 0 0.393 0.000826 0.474
32 SH2D6 SH2 domain containing 6 169691 2 2 2 0 0 1 0 1 0 0 0.473 0.000866 0.474
33 GNPAT glyceronephosphate O-acyltransferase 836793 3 3 3 0 0 1 1 1 0 0 0.375 0.000880 0.474
34 NLRP6 NLR family, pyrin domain containing 6 732725 3 3 1 0 0 0 3 0 0 0 0.579 0.000958 0.474
35 ZC3H15 zinc finger CCCH-type containing 15 482113 2 2 2 0 0 0 0 0 2 0 1.000 0.000987 0.474
BRAF

Figure S1.  This figure depicts the distribution of mutations and mutation types across the BRAF significant gene.

NRAS

Figure S2.  This figure depicts the distribution of mutations and mutation types across the NRAS significant gene.

HRAS

Figure S3.  This figure depicts the distribution of mutations and mutation types across the HRAS significant gene.

EIF1AX

Figure S4.  This figure depicts the distribution of mutations and mutation types across the EIF1AX significant gene.

CHEK2

Figure S5.  This figure depicts the distribution of mutations and mutation types across the CHEK2 significant gene.

S100A7

Figure S6.  This figure depicts the distribution of mutations and mutation types across the S100A7 significant gene.

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: 9. Number of genes displayed: 10

rank gene description n cos n_cos N_cos cos_ev p q
1 HRAS v-Ha-ras Harvey rat sarcoma viral oncogene homolog 14 19 14 7619 2912 8.8e-14 3.5e-10
2 NRAS neuroblastoma RAS viral (v-ras) oncogene homolog 34 33 34 13233 44132 1.5e-13 3.5e-10
3 BRAF v-raf murine sarcoma viral oncogene homolog B1 233 89 233 35689 3348968 4.1e-13 6.2e-10
4 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 4 52 4 20852 15200 2.5e-10 2.9e-07
5 C4BPA complement component 4 binding protein, alpha 1 1 1 401 1 0.00017 0.085
6 PCGF2 polycomb group ring finger 2 2 1 1 401 1 0.00017 0.085
7 SEZ6L seizure related 6 homolog (mouse)-like 2 1 1 401 1 0.00017 0.085
8 SMC3 structural maintenance of chromosomes 3 1 1 1 401 1 0.00017 0.085
9 TNS1 tensin 1 3 1 1 401 1 0.00017 0.085
10 DCC deleted in colorectal carcinoma 2 3 1 1203 1 0.00051 0.21

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
361 BRAF v-raf murine sarcoma viral oncogene homolog B1 233 0 26796 27028 27028 26796 27028 27028
2135 NRAS neuroblastoma RAS viral (v-ras) oncogene homolog 34 0 561 561 561 561 561 561
1457 HRAS v-Ha-ras Harvey rat sarcoma viral oncogene homolog 14 0 91 91 91 91 91 91
2269 OTUD4 OTU domain containing 4 5 0 10 10 10 10 10 10
994 EIF1AX eukaryotic translation initiation factor 1A, X-linked 6 0 4 7 7 4 7 7
2159 NUP93 nucleoporin 93kDa 4 0 3 6 6 3 6 6
1670 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 4 0 3 3 3 3 3 3
2112 NLRP6 NLR family, pyrin domain containing 6 3 0 3 3 3 3 3 3
184 AP3B1 adaptor-related protein complex 3, beta 1 subunit 4 0 1 3 3 1 3 3
117 AKT1 v-akt murine thymoma viral oncogene homolog 1 3 0 1 1 1 1 1 1

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: 86. 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_ns_s p q
1 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 202 ABI2(1), APC(2), ARHGEF4(1), ARHGEF6(1), ARHGEF7(1), BDKRB2(1), BRAF(233), CDC42(1), CHRM4(1), CHRM5(1), EZR(1), FGD1(1), FGD3(1), FGF20(1), FGF5(1), FGF7(1), FGFR2(1), FN1(1), HRAS(14), ITGA10(1), ITGA3(2), ITGA7(1), ITGA8(1), ITGAD(2), ITGAL(4), ITGAM(2), ITGAV(1), ITGB1(2), ITGB3(1), ITGB8(1), KRAS(4), MYH10(1), MYH14(1), MYLK(3), MYLPF(1), NCKAP1L(1), NRAS(34), PAK3(1), PAK7(2), PDGFRB(1), PIK3CA(2), PIK3CB(1), PIK3CD(1), PIK3CG(1), PIK3R1(1), PIK3R5(3), PIP4K2C(1), PIP5K1A(1), SOS1(1), SSH3(1), TIAM2(3), VCL(1) 164963682 349 302 73 28 12 17 46 265 9 0 7.5e-13 <1.00e-15 <5.60e-14
2 HSA04910_INSULIN_SIGNALING_PATHWAY Genes involved in insulin signaling pathway ACACA, ACACB, AKT1, AKT2, AKT3, ARAF, BAD, BRAF, CALM1, CALM2, CALM3, CALML3, CALML6, CBL, CBLB, CBLC, CRK, CRKL, EIF4EBP1, ELK1, EXOC7, FASN, FBP1, FBP2, FLOT1, FLOT2, FOXO1, FRAP1, G6PC, G6PC2, GCK, GRB2, GSK3B, GYS1, GYS2, HRAS, IKBKB, INPP5D, INS, INSR, IRS1, IRS2, IRS4, KIAA1303, KRAS, LIPE, MAP2K1, MAP2K2, MAPK1, MAPK10, MAPK3, MAPK8, MAPK9, MKNK1, MKNK2, NRAS, PCK1, PCK2, PDE3A, PDE3B, PDPK1, PFKL, PFKM, PFKP, PHKA1, PHKA2, PHKB, PHKG1, PHKG2, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PKLR, PKM2, PPARGC1A, PPP1CA, PPP1CB, PPP1CC, PPP1R3A, PPP1R3B, PPP1R3C, PPP1R3D, PRKAA1, PRKAA2, PRKAB1, PRKAB2, PRKACA, PRKACB, PRKACG, PRKAG1, PRKAG2, PRKAG3, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKCI, PRKCZ, PRKX, PRKY, PTPN1, PTPRF, PYGB, PYGL, PYGM, RAF1, RAPGEF1, RHEB, RHOQ, RPS6, RPS6KB1, RPS6KB2, SH2B2, SHC1, SHC2, SHC3, SHC4, SKIP, SLC2A4, SOCS1, SOCS2, SOCS3, SOCS4, SORBS1, SOS1, SOS2, SREBF1, TRIP10, TSC1, TSC2 131 ACACA(1), ACACB(1), AKT1(3), AKT2(1), BRAF(233), EXOC7(1), FASN(1), FLOT1(1), FLOT2(1), GYS2(1), HRAS(14), INPP5D(1), IRS1(1), IRS2(1), KRAS(4), MAPK10(1), NRAS(34), PCK2(1), PDE3A(1), PFKP(2), PHKA2(2), PIK3CA(2), PIK3CB(1), PIK3CD(1), PIK3CG(1), PIK3R1(1), PIK3R5(3), PPARGC1A(2), PPP1R3B(1), PRKAG2(1), PRKAR2A(1), PYGB(1), RAPGEF1(2), RHOQ(2), RPS6KB2(1), SHC1(1), SOS1(1), SREBF1(1), TRIP10(1) 95675123 330 296 53 21 11 9 45 261 4 0 5.7e-14 <1.00e-15 <5.60e-14
3 HSA04730_LONG_TERM_DEPRESSION Genes involved in long-term depression ARAF, BRAF, C7orf16, CACNA1A, CRH, CRHR1, GNA11, GNA12, GNA13, GNAI1, GNAI2, GNAI3, GNAO1, GNAQ, GNAS, GNAZ, GRIA1, GRIA2, GRIA3, GRID2, GRM1, GRM5, GUCY1A2, GUCY1A3, GUCY1B3, GUCY2C, GUCY2D, GUCY2F, HRAS, IGF1, IGF1R, ITPR1, ITPR2, ITPR3, KRAS, LYN, MAP2K1, MAP2K2, MAPK1, MAPK3, NOS1, NOS2A, NOS3, NPR1, NPR2, NRAS, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, PLCB1, PLCB2, PLCB3, PLCB4, PPP2CA, PPP2CB, PPP2R1A, PPP2R1B, PPP2R2A, PPP2R2B, PPP2R2C, PRKCA, PRKCB1, PRKCG, PRKG1, PRKG2, RAF1, RYR1 74 BRAF(233), CACNA1A(2), CRH(1), GNAS(3), GRIA1(1), GRIA2(2), GRID2(1), GRM1(2), GUCY1A3(1), HRAS(14), ITPR1(2), ITPR2(5), KRAS(4), LYN(1), NPR1(2), NRAS(34), PLA2G2A(1), PLA2G5(2), PLCB1(1), PLCB2(1), PLCB3(1), PPP2R1A(2), PPP2R1B(1), PRKG1(1), RYR1(4) 65706595 322 295 46 13 10 4 43 261 4 0 1.4e-15 <1.00e-15 <5.60e-14
4 HSA04650_NATURAL_KILLER_CELL_MEDIATED_CYTOTOXICITY Genes involved in natural killer cell mediated cytotoxicity ARAF, BID, BRAF, CASP3, CD244, CD247, CD48, CHP, CSF2, FAS, FASLG, FCER1G, FCGR3A, FCGR3B, FYN, GRB2, GZMB, HCST, HLA-A, HLA-B, HLA-C, HLA-E, HLA-G, HRAS, ICAM1, ICAM2, IFNA1, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA2, IFNA21, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNAR1, IFNAR2, IFNB1, IFNG, IFNGR1, IFNGR2, ITGAL, ITGB2, KIR2DL1, KIR2DL2, KIR2DL3, KIR2DL4, KIR2DL5A, KIR2DS1, KIR2DS2, KIR3DL1, KIR3DL2, KLRC1, KLRC2, KLRC3, KLRD1, KLRK1, KRAS, LAT, LCK, LCP2, LOC652578, MAP2K1, MAP2K2, MAPK1, MAPK3, MICA, MICB, NCR1, NCR2, NCR3, NFAT5, NFATC1, NFATC2, NFATC3, NFATC4, NRAS, PAK1, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PLCG1, PLCG2, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRF1, PRKCA, PRKCB1, PRKCG, PTK2B, PTPN11, PTPN6, RAC1, RAC2, RAC3, RAF1, SH2D1A, SH2D1B, SH3BP2, SHC1, SHC2, SHC3, SHC4, SOS1, SOS2, SYK, TNF, TNFRSF10A, TNFRSF10B, TNFRSF10C, TNFRSF10D, TNFSF10, TYROBP, ULBP1, ULBP2, ULBP3, VAV1, VAV2, VAV3, ZAP70 126 BRAF(233), HLA-E(1), HRAS(14), IFNAR2(1), IFNGR1(1), ITGAL(4), KIR2DL1(1), KIR3DL2(1), KRAS(4), LCK(1), NCR1(1), NFAT5(2), NFATC1(1), NFATC4(3), NRAS(34), PIK3CA(2), PIK3CB(1), PIK3CD(1), PIK3CG(1), PIK3R1(1), PIK3R5(3), PPP3R2(1), PTK2B(2), SHC1(1), SOS1(1), SYK(1), ULBP1(1) 67769087 318 292 42 19 8 7 43 256 4 0 1.4e-13 <1.00e-15 <5.60e-14
5 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(1), ABL2(1), AKT1(3), AKT2(1), BRAF(233), CAMK2A(1), CAMK2B(1), CDKN1A(1), ERBB2(1), ERBB3(1), ERBB4(1), HRAS(14), JUN(1), KRAS(4), MAPK10(1), MYC(1), NCK1(2), NRAS(34), NRG2(1), PAK3(1), PAK7(2), PIK3CA(2), PIK3CB(1), PIK3CD(1), PIK3CG(1), PIK3R1(1), PIK3R5(3), RPS6KB2(1), SHC1(1), SOS1(1), SRC(1), STAT5B(1) 61538069 320 291 43 11 7 7 45 255 5 1 2.4e-15 <1.00e-15 <5.60e-14
6 HSA04720_LONG_TERM_POTENTIATION Genes involved in long-term potentiation ADCY1, ADCY8, ARAF, ATF4, BRAF, CACNA1C, CALM1, CALM2, CALM3, CALML3, CALML6, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CAMK4, CHP, CREBBP, EP300, GNAQ, GRIA1, GRIA2, GRIN1, GRIN2A, GRIN2B, GRIN2C, GRIN2D, GRM1, GRM5, HRAS, ITPR1, ITPR2, ITPR3, KRAS, MAP2K1, MAP2K2, MAPK1, MAPK3, NRAS, PLCB1, PLCB2, PLCB3, PLCB4, PPP1CA, PPP1CB, PPP1CC, PPP1R12A, PPP1R1A, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRKACA, PRKACB, PRKACG, PRKCA, PRKCB1, PRKCG, PRKX, PRKY, RAF1, RAP1A, RAP1B, RAPGEF3, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KA6 67 BRAF(233), CACNA1C(1), CAMK2A(1), CAMK2B(1), CREBBP(1), GRIA1(1), GRIA2(2), GRIN2A(1), GRIN2B(3), GRIN2D(3), GRM1(2), HRAS(14), ITPR1(2), ITPR2(5), KRAS(4), NRAS(34), PLCB1(1), PLCB2(1), PLCB3(1), PPP3R2(1), RAP1A(1) 59336843 313 291 37 9 8 5 42 254 4 0 1.1e-15 <1.00e-15 <5.60e-14
7 MAPKPATHWAY The mitogen-activated protein (MAP) kinase pathway is a common signaling mechanism and has four main sub-pathways: Erk, JNK/SAPK, p53, and ERK5. ARAF1, ATF2, BRAF, CEBPA, CHUK, CREB1, DAXX, ELK1, FOS, GRB2, HRAS, IKBKB, JUN, MAP2K1, MAP2K2, MAP2K3, MAP2K4, MAP2K5, MAP2K6, MAP2K7, MAP3K1, MAP3K10, MAP3K11, MAP3K12, MAP3K13, MAP3K14, MAP3K2, MAP3K3, MAP3K4, MAP3K5, MAP3K6, MAP3K7, MAP3K8, MAP3K9, MAP4K1, MAP4K2, MAP4K3, MAP4K4, MAP4K5, MAPK1, MAPK10, MAPK11, MAPK12, MAPK13, MAPK14, MAPK3, MAPK4, MAPK6, MAPK7, MAPK8, MAPK9, MAPKAPK2, MAPKAPK3, MAPKAPK5, MAX, MEF2A, MEF2B, MEF2C, MEF2D, MKNK1, MKNK2, MYC, NFKB1, NFKBIA, PAK1, PAK2, PDZGEF1, RAC1, RAF1, RELA, RIPK1, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KA4, RPS6KA5, RPS6KB1, RPS6KB2, SHC1, SP1, STAT1, TGFB1, TGFB2, TGFB3, TGFBR1, TRADD, TRAF2 84 BRAF(233), HRAS(14), JUN(1), MAP2K6(1), MAP3K1(2), MAP3K3(3), MAP3K6(1), MAP4K4(1), MAPK10(1), MAPK4(1), MAPKAPK3(1), MEF2B(1), MYC(1), RPS6KB2(1), SHC1(1), SP1(1), STAT1(1) 56677716 265 254 22 7 5 3 14 241 2 0 1.3e-15 <1.00e-15 <5.60e-14
8 HSA04150_MTOR_SIGNALING_PATHWAY Genes involved in mTOR signaling pathway AKT1, AKT2, AKT3, BRAF, CAB39, DDIT4, EIF4B, EIF4EBP1, FIGF, FRAP1, GBL, HIF1A, IGF1, INS, KIAA1303, LYK5, MAPK1, MAPK3, PDPK1, PGF, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PRKAA1, PRKAA2, RHEB, RICTOR, RPS6, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KA6, RPS6KB1, RPS6KB2, STK11, TSC1, TSC2, ULK1, ULK2, ULK3, VEGFA, VEGFB, VEGFC 44 AKT1(3), AKT2(1), BRAF(233), FIGF(1), HIF1A(1), PIK3CA(2), PIK3CB(1), PIK3CD(1), PIK3CG(1), PIK3R1(1), PIK3R5(3), RPS6KB2(1), ULK3(1), VEGFA(1) 31723815 251 235 19 5 3 3 4 238 3 0 5e-15 <1.00e-15 <5.60e-14
9 ST_DIFFERENTIATION_PATHWAY_IN_PC12_CELLS Rat-derived PC12 cells respond to nerve growth factor (NGF) and PACAP to differentiate into neuronal cells. AKT1, ASAH1, ATF1, BRAF, CAMP, CREB1, CREB3, CREB5, CREBBP, CRKL, DAG1, EGR1, EGR2, EGR3, EGR4, ELK1, FRS2, GAS, GNAQ, GRF2, JUN, MAP1B, MAP2K4, MAP2K7, MAPK1, MAPK10, MAPK3, MAPK8, MAPK8IP1, MAPK8IP2, MAPK8IP3, MAPK9, NTRK1, OPN1LW, PACAP, PIK3C2G, PIK3CA, PIK3CD, PIK3R1, PTPN11, RPS6KA3, SH2B, SHC1, SRC, TERF2IP, TH, TUBA3 42 AKT1(3), BRAF(233), CREBBP(1), JUN(1), MAP1B(3), MAPK10(1), MAPK8IP2(1), PIK3C2G(1), PIK3CA(2), PIK3CD(1), PIK3R1(1), SHC1(1), SRC(1) 30661073 250 235 18 6 4 5 1 238 2 0 5.6e-15 <1.00e-15 <5.60e-14
10 ST_ERK1_ERK2_MAPK_PATHWAY The Erk1 and Erk2 MAP kinase pathways are regulated by Raf, Mos, and Tpl-2. ARAF1, ATF1, BAD, BRAF, COPEB, CREB1, CREB3, CREB5, DUSP4, DUSP6, DUSP9, EEF2K, EIF4E, GRB2, HTATIP, MAP2K1, MAP2K2, MAP3K8, MAPK1, MAPK3, MKNK1, MKNK2, MOS, NFKB1, RAP1A, RPS6KA1, RPS6KA2, RPS6KA3, SHC1, SOS1, SOS2, TRAF3 29 BRAF(233), EEF2K(1), RAP1A(1), SHC1(1), SOS1(1) 17612614 237 234 6 4 1 2 1 233 0 0 1.1e-14 <1.00e-15 <5.60e-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_ns_s p q
1 PLK3PATHWAY Active Plk3 phosphorylates CDC25c, blocking the G2/M transition, and phosphorylates p53 to induce apoptosis. ATM, ATR, CDC25C, CHEK1, CHEK2, CNK, TP53, YWHAH 6 ATM(5), ATR(3), CHEK1(1), TP53(3) 8876595 12 12 12 1 0 2 1 3 6 0 0.18 0.00031 0.12
2 P53PATHWAY p53 induces cell cycle arrest or apoptosis under conditions of DNA damage. APAF1, ATM, BAX, BCL2, CCND1, CCNE1, CDK2, CDK4, CDKN1A, E2F1, GADD45A, MDM2, PCNA, RB1, TIMP3, TP53 16 APAF1(2), ATM(5), CDKN1A(1), RB1(2), TP53(3) 10776233 13 13 13 0 1 3 1 3 5 0 0.038 0.0004 0.12
3 ARFPATHWAY Cyclin-dependent kinase inhibitor 2A is a tumor suppressor that induces G1 arrest and can activate the p53 pathway, leading to G2/M arrest. ABL1, CDKN2A, E2F1, MDM2, MYC, PIK3CA, PIK3R1, POLR1A, POLR1B, POLR1C, POLR1D, RAC1, RB1, TBX2, TP53, TWIST1 16 ABL1(1), MYC(1), PIK3CA(2), PIK3R1(1), POLR1A(1), POLR1B(2), RB1(2), TP53(3), TWIST1(1) 12103349 14 14 14 0 2 2 1 2 7 0 0.014 0.00058 0.12
4 ATRBRCAPATHWAY BRCA1 and 2 block cell cycle progression in response to DNA damage and promote double-stranded break repair; mutations induce breast cancer susceptibility. ATM, ATR, BRCA1, BRCA2, CHEK1, CHEK2, FANCA, FANCC, FANCD2, FANCE, FANCF, FANCG, HUS1, MRE11A, NBS1, RAD1, RAD17, RAD50, RAD51, RAD9A, TP53, TREX1 20 ATM(5), ATR(3), BRCA1(1), BRCA2(3), CHEK1(1), FANCD2(3), FANCF(1), FANCG(2), TP53(3), TREX1(1) 25594645 23 22 23 2 0 5 4 5 9 0 0.042 0.00096 0.15
5 ATMPATHWAY The tumor-suppressing protein kinase ATM responds to radiation-induced DNA damage by blocking cell-cycle progression and activating DNA repair. ABL1, ATM, BRCA1, CDKN1A, CHEK1, CHEK2, GADD45A, JUN, MAPK8, MDM2, MRE11A, NBS1, NFKB1, NFKBIA, RAD50, RAD51, RBBP8, RELA, TP53, TP73 18 ABL1(1), ATM(5), BRCA1(1), CDKN1A(1), CHEK1(1), JUN(1), TP53(3), TP73(3) 17117771 16 16 16 0 1 6 2 3 4 0 0.0083 0.0014 0.15
6 P53HYPOXIAPATHWAY Hypoxia induces p53 accumulation and consequent apoptosis with p53-mediated cell cycle arrest, which is present under conditions of DNA damage. ABCB1, AKT1, ATM, BAX, CDKN1A, CPB2, CSNK1A1, CSNK1D, FHL2, GADD45A, HIC1, HIF1A, HSPA1A, HSPCA, IGFBP3, MAPK8, MDM2, NFKBIB, NQO1, TP53 19 AKT1(3), ATM(5), CDKN1A(1), HIF1A(1), TP53(3) 12386283 13 13 12 1 0 3 2 4 4 0 0.11 0.0015 0.15
7 SA_PTEN_PATHWAY PTEN is a tumor suppressor that dephosphorylates the lipid messenger phosphatidylinositol triphosphate. AKT1, AKT2, AKT3, BPNT1, GRB2, ILK, MAPK1, MAPK3, PDK1, PIK3CA, PIK3CD, PIP3-E, PTEN, PTK2B, RBL2, SHC1, SOS1 16 AKT1(3), AKT2(1), PIK3CA(2), PIK3CD(1), PTEN(2), PTK2B(2), RBL2(1), SHC1(1), SOS1(1) 12167714 14 14 13 2 2 6 0 4 1 1 0.13 0.0023 0.2
8 HCMVPATHWAY Cytomegalovirus activates MAP kinase pathways in the host cell, inducing transcription of viral genes. AKT1, CREB1, MAP2K1, MAP2K2, MAP2K3, MAP2K6, MAP3K1, MAPK1, MAPK14, MAPK3, NFKB1, PIK3CA, PIK3R1, RB1, RELA, SP1 16 AKT1(3), MAP2K6(1), MAP3K1(2), PIK3CA(2), PIK3R1(1), RB1(2), SP1(1) 11567390 12 12 11 1 1 3 1 5 2 0 0.12 0.0026 0.2
9 RBPATHWAY The ATM protein kinase recognizes DNA damage and blocks cell cycle progression by phosphorylating chk1 and p53, which normally inhibits Rb to allow G1/S transitions. ATM, CDC2, CDC25A, CDC25B, CDC25C, CDK2, CDK4, CHEK1, MYT1, RB1, TP53, WEE1, YWHAH 12 ATM(5), CHEK1(1), RB1(2), TP53(3) 10465688 11 11 11 0 1 3 1 2 4 0 0.044 0.0034 0.23
10 TERTPATHWAY hTERC, the RNA subunit of telomerase, and hTERT, the catalytic protein subunit, are required for telomerase activity and are overexpressed in many cancers. HDAC1, MAX, MYC, SP1, SP3, TP53, WT1, ZNF42 7 MYC(1), SP1(1), TP53(3), WT1(1) 4217884 6 6 6 0 0 0 2 1 3 0 0.16 0.0063 0.39
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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