Mutation Analysis (MutSig v2.0)
Prostate Adenocarcinoma (Primary solid tumor)
02 April 2015  |  analyses__2015_04_02
Maintainer Information
Citation Information
doi:10.7908/C1RB73P6
Maintained by David Heiman (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2015): Mutation Analysis (MutSig v2.0). Broad Institute of MIT and Harvard. doi:10.7908/C1RB73P6
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 was used to generate the results found in this report.

  • Working with individual set: PRAD-TP

  • Number of patients in set: 425

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:PRAD-TP.final_analysis_set.maf

  • Blacklist used for this analysis: pancan_mutation_blacklist.v14.hg19.txt

  • Significantly mutated genes (q ≤ 0.1): 31

  • Mutations seen in COSMIC: 141

  • Significantly mutated genes in COSMIC territory: 10

  • Significantly mutated genesets: 28

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

Mutation Preprocessing

  • Read 425 MAFs of type "Broad"

  • Total number of mutations in input MAFs: 27263

  • After removing 32 mutations outside chr1-24: 27231

  • After removing 2679 blacklisted mutations: 24552

  • After removing 1514 noncoding mutations: 23038

  • After collapsing adjacent/redundant mutations: 20845

Mutation Filtering

  • Number of mutations before filtering: 20845

  • After removing 1098 mutations outside gene set: 19747

  • After removing 14 mutations outside category set: 19733

Results
Breakdown of Mutations by Type

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

type count
Frame_Shift_Del 893
Frame_Shift_Ins 263
In_Frame_Del 241
In_Frame_Ins 26
Missense_Mutation 12036
Nonsense_Mutation 737
Nonstop_Mutation 17
Silent 4761
Splice_Site 680
Translation_Start_Site 79
Total 19733
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 4236 685631561 6.2e-06 6.2 5.1 2.1
*Cp(A/C/T)->T 2049 5637152276 3.6e-07 0.36 0.3 1.7
A->G 1674 6093491283 2.7e-07 0.27 0.23 2.3
transver 4152 12416275120 3.3e-07 0.33 0.28 5
indel+null 2848 12416275120 2.3e-07 0.23 0.19 NaN
double_null 13 12416275120 1e-09 0.001 0.00087 NaN
Total 14972 12416275120 1.2e-06 1.2 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). If the figure is unpopulated, then full coverage is assumed (e.g. MutSig CV doesn't use WIGs and assumes full coverage).

Figure 1. 

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

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

Lego Plots

The mutation spectrum is depicted in the lego plots below in which the 96 possible mutation types are subdivided into six large blocks, color-coded to reflect the base substitution type. Each large block is further subdivided into the 16 possible pairs of 5' and 3' neighbors, as listed in the 4x4 trinucleotide context legend. The height of each block corresponds to the mutation frequency for that kind of mutation (counts of mutations normalized by the base coverage in a given bin). The shape of the spectrum is a signature for dominant mutational mechanisms in different tumor types.

Figure 3.  Get High-res Image SNV Mutation rate lego plot for entire set. Each bin is normalized by base coverage for that bin. Colors represent the six SNV types on the upper right. The three-base context for each mutation is labeled in the 4x4 legend on the lower right. The fractional breakdown of SNV counts is shown in the pie chart on the upper left. If this figure is blank, not enough information was provided in the MAF to generate it.

Figure 4.  Get High-res Image SNV Mutation rate lego plots for 4 slices of mutation allele fraction (0<=AF<0.1, 0.1<=AF<0.25, 0.25<=AF<0.5, & 0.5<=AF) . The color code and three-base context legends are the same as the previous figure. If this figure is blank, not enough information was provided in the MAF to generate it.

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_classic = p-value for the observed amount of nonsilent mutations being elevated in this gene

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

  • 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: 31. 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_classic p_ns_s p_clust p_cons p_joint p q
1 SPOP speckle-type POZ protein 493289 49 48 15 0 1 0 8 38 2 0 <1.00e-15 0.000091 0 0.15 0 <1.00e-15 <3.02e-12
2 TP53 tumor protein p53 513678 44 43 34 0 13 6 5 7 13 0 5.11e-15 0.000016 6e-07 0.000013 0 <1.00e-15 <3.02e-12
3 FOXA1 forkhead box A1 450201 25 25 17 2 1 2 3 6 12 1 7.33e-15 0.21 0 0.026 0 <1.00e-15 <3.02e-12
4 CTNNB1 catenin (cadherin-associated protein), beta 1, 88kDa 1019744 11 11 8 0 0 1 3 7 0 0 1.08e-08 0.042 0 0.012 0 <1.00e-15 <3.02e-12
5 KIDINS220 kinase D-interacting substrate, 220kDa 2304669 3 3 3 1 0 0 0 2 1 0 0.380 0.75 0.15 0 0 <1.00e-15 <3.02e-12
6 SLC27A4 solute carrier family 27 (fatty acid transporter), member 4 821905 2 2 2 1 0 0 1 0 1 0 0.219 0.88 0.18 0 0 <1.00e-15 <3.02e-12
7 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 496516 14 14 14 0 0 0 1 3 10 0 1.35e-14 0.21 0.14 0.86 0.21 9.93e-14 2.57e-10
8 IDH1 isocitrate dehydrogenase 1 (NADP+), soluble 538265 5 5 2 0 4 0 0 1 0 0 0.000101 0.2 1.8e-06 0.79 0.000014 2.95e-08 6.67e-05
9 ATM ataxia telangiectasia mutated 3973837 19 19 19 2 1 6 2 7 3 0 3.99e-07 0.17 0.29 0.0064 0.017 1.33e-07 0.000268
10 EMG1 EMG1 nucleolar protein homolog (S. cerevisiae) 276669 4 4 2 0 0 0 0 0 4 0 5.66e-05 1 0.00024 0.89 0.00056 5.77e-07 0.00104
11 BRAF v-raf murine sarcoma viral oncogene homolog B1 947390 8 8 7 0 0 0 2 5 1 0 7.05e-06 0.16 0.012 0.014 0.0052 6.58e-07 0.00108
12 NKX3-1 NK3 homeobox 1 218518 5 5 5 0 0 0 2 2 1 0 3.16e-06 0.42 0.14 0.0072 0.031 1.66e-06 0.00250
13 OR4P4 olfactory receptor, family 4, subfamily P, member 4 370433 5 5 4 0 3 0 0 1 1 0 1.77e-06 0.22 0.11 0.086 0.076 2.26e-06 0.00314
14 MED12 mediator complex subunit 12 2261211 6 6 3 1 0 3 0 3 0 0 0.0268 0.39 1.2e-06 0.15 9.4e-06 4.08e-06 0.00527
15 OR4D5 olfactory receptor, family 4, subfamily D, member 5 408397 6 6 6 0 3 2 0 1 0 0 2.85e-07 0.11 0.91 0.36 1 4.59e-06 0.00553
16 COL11A1 collagen, type XI, alpha 1 2401276 11 11 11 1 3 1 2 4 1 0 6.12e-06 0.1 0.07 0.4 0.13 1.17e-05 0.0130
17 NTM neurotrimin 495453 6 6 6 0 2 1 0 1 2 0 1.23e-05 0.082 NaN NaN NaN 1.23e-05 0.0130
18 HRAS v-Ha-ras Harvey rat sarcoma viral oncogene homolog 274530 5 5 3 0 2 0 3 0 0 0 6.22e-06 0.28 0.2 0.68 0.26 2.33e-05 0.0234
19 LCE2D late cornified envelope 2D 143225 4 4 4 0 2 0 0 1 1 0 2.37e-06 0.68 0.96 0.21 0.89 2.96e-05 0.0276
20 BHLHE22 basic helix-loop-helix family, member e22 169103 3 3 2 0 0 0 0 0 3 0 0.000472 1 0.00088 0.97 0.0046 3.05e-05 0.0276
21 LMOD2 leiomodin 2 (cardiac) 421319 5 5 3 0 0 0 0 2 3 0 2.71e-05 0.7 0.43 0.043 0.089 3.38e-05 0.0291
22 EPB41L3 erythrocyte membrane protein band 4.1-like 3 1416948 11 10 11 1 6 2 1 2 0 0 9.07e-06 0.06 0.18 0.46 0.29 3.69e-05 0.0303
23 SALL1 sal-like 1 (Drosophila) 1674558 9 9 9 1 3 2 2 2 0 0 0.000111 0.094 0.025 0.24 0.033 4.96e-05 0.0391
24 RAG1 recombination activating gene 1 1331690 9 9 9 0 6 1 1 1 0 0 4.42e-06 0.09 0.75 0.43 0.9 5.35e-05 0.0398
25 KDM6A lysine (K)-specific demethylase 6A 1583487 9 9 9 1 0 0 1 1 7 0 1.92e-05 0.49 0.82 0.042 0.21 5.50e-05 0.0398
26 MUC17 mucin 17, cell surface associated 5750471 26 25 26 6 1 14 2 7 2 0 7.32e-05 0.17 0.036 0.79 0.082 7.80e-05 0.0543
27 ANO4 anoctamin 4 1214742 8 8 8 0 2 0 0 4 2 0 5.36e-05 0.13 0.31 0.053 0.14 9.64e-05 0.0646
28 RPL11 ribosomal protein L11 199370 4 4 4 0 0 1 2 0 1 0 1.09e-05 0.3 0.82 0.81 1 0.000136 0.0838
29 GRIA1 glutamate receptor, ionotropic, AMPA 1 1231367 10 10 8 2 7 0 0 3 0 0 9.68e-05 0.31 0.071 0.71 0.11 0.000137 0.0838
30 ZMYM3 zinc finger, MYM-type 3 1185165 10 9 10 0 0 0 0 4 6 0 1.65e-05 0.31 0.5 0.69 0.68 0.000139 0.0838
31 LILRB5 leukocyte immunoglobulin-like receptor, subfamily B (with TM and ITIM domains), member 5 739094 9 9 6 3 1 2 4 2 0 0 2.63e-05 0.59 0.36 0.48 0.53 0.000169 0.0988
32 PLCB4 phospholipase C, beta 4 1569155 8 8 8 0 0 3 0 4 1 0 0.000204 0.16 0.061 0.12 0.073 0.000179 0.101
33 APC adenomatous polyposis coli 3641798 9 9 9 0 1 1 0 0 7 0 0.00782 0.23 0.00087 0.96 0.0021 0.000194 0.106
34 OR5D18 olfactory receptor, family 5, subfamily D, member 18 401533 5 5 5 0 2 1 1 1 0 0 2.25e-05 0.14 0.54 0.88 0.75 0.000202 0.107
35 GIGYF2 GRB10 interacting GYF protein 2 1563667 8 8 8 0 1 0 2 2 3 0 0.000266 0.16 0.38 0.037 0.071 0.000225 0.116
SPOP

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

TP53

Figure S2.  This figure depicts the distribution of mutations and mutation types across the TP53 significant gene.

FOXA1

Figure S3.  This figure depicts the distribution of mutations and mutation types across the FOXA1 significant gene.

CTNNB1

Figure S4.  This figure depicts the distribution of mutations and mutation types across the CTNNB1 significant gene.

KIDINS220

Figure S5.  This figure depicts the distribution of mutations and mutation types across the KIDINS220 significant gene.

SLC27A4

Figure S6.  This figure depicts the distribution of mutations and mutation types across the SLC27A4 significant gene.

PTEN

Figure S7.  This figure depicts the distribution of mutations and mutation types across the PTEN significant gene.

IDH1

Figure S8.  This figure depicts the distribution of mutations and mutation types across the IDH1 significant gene.

ATM

Figure S9.  This figure depicts the distribution of mutations and mutation types across the ATM significant gene.

EMG1

Figure S10.  This figure depicts the distribution of mutations and mutation types across the EMG1 significant gene.

BRAF

Figure S11.  This figure depicts the distribution of mutations and mutation types across the BRAF significant gene.

NKX3-1

Figure S12.  This figure depicts the distribution of mutations and mutation types across the NKX3-1 significant gene.

OR4P4

Figure S13.  This figure depicts the distribution of mutations and mutation types across the OR4P4 significant gene.

MED12

Figure S14.  This figure depicts the distribution of mutations and mutation types across the MED12 significant gene.

OR4D5

Figure S15.  This figure depicts the distribution of mutations and mutation types across the OR4D5 significant gene.

COL11A1

Figure S16.  This figure depicts the distribution of mutations and mutation types across the COL11A1 significant gene.

NTM

Figure S17.  This figure depicts the distribution of mutations and mutation types across the NTM significant gene.

HRAS

Figure S18.  This figure depicts the distribution of mutations and mutation types across the HRAS significant gene.

LCE2D

Figure S19.  This figure depicts the distribution of mutations and mutation types across the LCE2D significant gene.

BHLHE22

Figure S20.  This figure depicts the distribution of mutations and mutation types across the BHLHE22 significant gene.

LMOD2

Figure S21.  This figure depicts the distribution of mutations and mutation types across the LMOD2 significant gene.

EPB41L3

Figure S22.  This figure depicts the distribution of mutations and mutation types across the EPB41L3 significant gene.

SALL1

Figure S23.  This figure depicts the distribution of mutations and mutation types across the SALL1 significant gene.

RAG1

Figure S24.  This figure depicts the distribution of mutations and mutation types across the RAG1 significant gene.

KDM6A

Figure S25.  This figure depicts the distribution of mutations and mutation types across the KDM6A significant gene.

MUC17

Figure S26.  This figure depicts the distribution of mutations and mutation types across the MUC17 significant gene.

ANO4

Figure S27.  This figure depicts the distribution of mutations and mutation types across the ANO4 significant gene.

RPL11

Figure S28.  This figure depicts the distribution of mutations and mutation types across the RPL11 significant gene.

GRIA1

Figure S29.  This figure depicts the distribution of mutations and mutation types across the GRIA1 significant gene.

ZMYM3

Figure S30.  This figure depicts the distribution of mutations and mutation types across the ZMYM3 significant gene.

LILRB5

Figure S31.  This figure depicts the distribution of mutations and mutation types across the LILRB5 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: 10. Number of genes displayed: 10

rank gene description n cos n_cos N_cos cos_ev p q
1 IDH1 isocitrate dehydrogenase 1 (NADP+), soluble 5 5 5 2125 7460 0 0
2 TP53 tumor protein p53 44 356 42 151300 10513 0 0
3 CTNNB1 catenin (cadherin-associated protein), beta 1, 88kDa 11 138 10 58650 3980 0 0
4 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 12 220 11 93500 2941 0 0
5 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 14 767 14 325975 201 0 0
6 BRAF v-raf murine sarcoma viral oncogene homolog B1 8 89 6 37825 14422 1.1e-11 8.6e-09
7 SMAD4 SMAD family member 4 5 159 5 67575 21 2.8e-08 0.000018
8 HRAS v-Ha-ras Harvey rat sarcoma viral oncogene homolog 5 19 3 8075 624 1.5e-07 0.000086
9 APC adenomatous polyposis coli 9 839 7 356575 82 3.7e-07 0.00019
10 ATM ataxia telangiectasia mutated 19 245 4 104125 9 9.4e-06 0.0042

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: 28. 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 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(4), CDKN2A(1), MDM2(1), MYC(1), PIK3CA(12), PIK3R1(1), POLR1A(3), POLR1B(2), POLR1C(2), RAC1(1), RB1(2), TP53(44) 12835679 74 64 63 3 18 9 10 18 18 1 4.5e-06 <1.00e-15 <3.42e-13
2 CHEMICALPATHWAY DNA damage promotes Bid cleavage, which stimulates mitochondrial cytochrome c release and consequent caspase activation, resulting in apoptosis. ADPRT, AKT1, APAF1, ATM, BAD, BAX, BCL2, BCL2L1, BID, CASP3, CASP6, CASP7, CASP9, CYCS, EIF2S1, PRKCA, PRKCB1, PTK2, PXN, STAT1, TLN1, TP53 20 AKT1(3), APAF1(1), ATM(19), PRKCA(2), PTK2(2), PXN(2), STAT1(1), TLN1(2), TP53(44) 17314480 76 69 65 3 17 16 7 18 18 0 2e-06 2.89e-15 3.42e-13
3 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 19 ABL1(4), ATM(19), BRCA1(1), CDKN1A(2), MDM2(1), RAD51(1), RELA(2), TP53(44) 18857861 74 63 64 2 17 13 9 16 19 0 1.9e-06 3.00e-15 3.42e-13
4 PLK3PATHWAY Active Plk3 phosphorylates CDC25c, blocking the G2/M transition, and phosphorylates p53 to induce apoptosis. ATM, ATR, CDC25C, CHEK1, CHEK2, CNK, TP53, YWHAH 7 ATM(19), ATR(2), TP53(44), YWHAH(1) 10128130 66 59 56 3 15 13 7 15 16 0 0.00016 3.44e-15 3.42e-13
5 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(1), ATM(19), CDKN1A(2), MDM2(1), PCNA(1), RB1(2), TP53(44) 11449972 70 63 60 4 16 13 8 14 18 1 0.000045 3.55e-15 3.42e-13
6 SA_G1_AND_S_PHASES Cdk2, 4, and 6 bind cyclin D in G1, while cdk2/cyclin E promotes the G1/S transition. ARF1, ARF3, CCND1, CDK2, CDK4, CDKN1A, CDKN1B, CDKN2A, CFL1, E2F1, E2F2, MDM2, NXT1, PRB1, TP53 15 CDKN1A(2), CDKN1B(5), CDKN2A(1), CFL1(1), MDM2(1), TP53(44) 5318254 54 51 44 2 15 6 5 7 21 0 0.00015 4.00e-15 3.42e-13
7 RNAPATHWAY dsRNA-activated protein kinase phosphorylates elF2a, which generally inhibits translation, and activates NF-kB to provoke inflammation. CHUK, DNAJC3, EIF2S1, EIF2S2, MAP3K14, NFKB1, NFKBIA, PRKR, RELA, TP53 9 RELA(2), TP53(44) 6125460 46 43 36 1 13 7 6 7 13 0 0.000067 4.00e-15 3.42e-13
8 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 ABCB1(4), AKT1(3), ATM(19), CDKN1A(2), CPB2(1), HIC1(3), MDM2(1), NFKBIB(1), NQO1(1), TP53(44) 13113380 79 71 68 3 21 15 8 16 19 0 9.8e-07 4.44e-15 3.42e-13
9 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(2), SP3(3), TP53(44) 4446201 50 47 40 1 13 7 5 10 15 0 0.000012 5.11e-15 3.50e-13
10 PMLPATHWAY Ring-shaped PML nuclear bodies regulate transcription and are required co-activators in p53- and DAXX-mediated apoptosis. CREBBP, DAXX, HRAS, PAX3, PML, PRAM-1, RARA, RB1, SIRT1, SP100, TNF, TNFRSF1A, TNFRSF1B, TNFRSF6, TNFSF6, TP53, UBL1 13 CREBBP(5), DAXX(1), HRAS(5), PAX3(3), PML(3), RB1(2), SIRT1(2), SP100(2), TNF(1), TP53(44) 11978829 68 64 56 6 22 8 13 10 14 1 0.00012 6.55e-15 4.03e-13

Table 6.  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 LONGEVITYPATHWAY Caloric restriction in animals often increases lifespan, which may occur via decreased IGF receptor expression and consequent expression of stress-resistance proteins. AKT1, CAT, FOXO3A, GH1, GHR, HRAS, IGF1, IGF1R, PIK3CA, PIK3R1, SHC1, SOD1, SOD2, SOD3 12 AKT1(3), CAT(2), GH1(2), GHR(1), IGF1R(2), PIK3CA(12), PIK3R1(1), SHC1(2), SOD2(1), SOD3(1) 8140334 27 26 25 3 6 6 4 9 2 0 0.038 0.00061 0.38
2 HSA00902_MONOTERPENOID_BIOSYNTHESIS Genes involved in monoterpenoid biosynthesis CYP2C19, CYP2C9 2 CYP2C19(3), CYP2C9(2) 1280663 5 5 5 0 3 1 0 1 0 0 0.25 0.0024 0.76
3 PTENPATHWAY PTEN suppresses AKT-induced cell proliferation and antagonizes the action of PI3K. AKT1, BCAR1, CDKN1B, FOXO3A, GRB2, ILK, ITGB1, MAPK1, MAPK3, PDK2, PDPK1, PIK3CA, PIK3R1, PTEN, PTK2, SHC1, SOS1, TNFSF6 15 AKT1(3), BCAR1(1), CDKN1B(5), GRB2(1), MAPK1(1), PDK2(1), PDPK1(1), PIK3CA(12), PIK3R1(1), PTK2(2), SHC1(2), SOS1(1) 11641639 31 27 29 3 8 8 2 7 6 0 0.027 0.0077 1
4 AKTPATHWAY Second messenger PIP3 promotes cell survival by activating the anti-apoptotic kinase AKT. AKT1, BAD, CASP9, CHUK, FOXO1A, FOXO3A, GH1, GHR, HSPCA, MLLT7, NFKB1, NFKBIA, PDPK1, PIK3CA, PIK3R1, PPP2CA, RELA, TNFSF6, YWHAH 14 AKT1(3), GH1(2), GHR(1), PDPK1(1), PIK3CA(12), PIK3R1(1), PPP2CA(1), RELA(2), YWHAH(1) 8894992 24 23 22 3 4 8 3 8 1 0 0.059 0.0086 1
5 NEUROTRANSMITTERSPATHWAY Biosynthesis of neurotransmitters DBH, GAD1, HDC, PNMT, TH, TPH1 6 DBH(5), GAD1(2), HDC(1), PNMT(1), TPH1(1) 3802340 10 10 10 0 5 1 2 2 0 0 0.03 0.025 1
6 ACETAMINOPHENPATHWAY Acetaminophen selectively inhibits Cox-3, which is localized to the brain, and yields the toxic metabolite NAPQI when processed by CAR in the liver. CYP1A2, CYP2E1, CYP3A, NR1I3, PTGS1, PTGS2 5 CYP1A2(1), NR1I3(2), PTGS1(2), PTGS2(3) 3380190 8 8 8 1 2 3 0 2 1 0 0.2 0.029 1
7 TRKAPATHWAY Nerve growth factor (NGF) promotes neuronal survival and proliferation by binding its receptor TrkA, which activates PI3K/AKT, Ras, and the MAP kinase pathway. AKT1, DPM2, GRB2, HRAS, KLK2, NGFB, NTRK1, PIK3CA, PIK3R1, PLCG1, PRKCA, PRKCB1, SHC1, SOS1 11 AKT1(3), GRB2(1), KLK2(1), NTRK1(4), PIK3CA(12), PIK3R1(1), PLCG1(1), PRKCA(2), SHC1(2), SOS1(1) 9556750 28 24 26 4 8 9 2 7 2 0 0.055 0.034 1
8 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 25 AKT1(3), APC(9), CD14(1), FZD1(2), GJA1(1), GNAI1(1), GSK3B(1), IRAK1(1), LEF1(2), LY96(1), PDPK1(1), PIK3CA(12), PIK3R1(1), PPP2CA(1), RELA(2), TLR4(1) 18339151 40 38 38 5 9 9 5 8 9 0 0.0084 0.041 1
9 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 15 ABL1(4), CDKN2A(1), MDM2(1), MYC(1), PIK3CA(12), PIK3R1(1), POLR1A(3), POLR1B(2), POLR1C(2), RAC1(1), RB1(2) 12322001 30 24 29 3 5 3 5 11 5 1 0.045 0.058 1
10 FATTY_ACID_BIOSYNTHESIS_PATH_2 ACAA1, ACAA2, ACAT1, ACAT2, ECHS1, EHHADH, HADHA, HADHB, SDS 9 ACAA1(2), ACAA2(1), ACAT1(1), EHHADH(5), HADHB(1) 5278494 10 10 10 0 3 1 1 3 2 0 0.073 0.067 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

In addition to the links below, the full results of the analysis summarized in this report can also be downloaded programmatically using firehose_get, or interactively from either the Broad GDAC website or TCGA Data Coordination Center Portal.

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