Mutation Analysis (MutSig v2.0)
Glioma (Primary solid tumor)
21 August 2015  |  analyses__2015_08_21
Maintainer Information
Citation Information
doi:10.7908/C1G44PH9
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/C1G44PH9
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: GBMLGG-TP

  • Number of patients in set: 796

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:GBMLGG-TP.final_analysis_set.maf

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

  • Significantly mutated genes (q ≤ 0.1): 116

  • Mutations seen in COSMIC: 1403

  • Significantly mutated genes in COSMIC territory: 72

  • Significantly mutated genesets: 105

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

Mutation Preprocessing

  • Read 796 MAFs of type "maf1"

  • Total number of mutations in input MAFs: 66602

  • After removing 17 mutations outside chr1-24: 66585

  • After removing 3696 blacklisted mutations: 62889

  • After removing 3169 noncoding mutations: 59720

Mutation Filtering

  • Number of mutations before filtering: 59720

  • After removing 3049 mutations outside gene set: 56671

  • After removing 189 mutations outside category set: 56482

  • After removing 2 "impossible" mutations in

  • gene-patient-category bins of zero coverage: 53242

Results
Breakdown of Mutations by Type

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

type count
De_novo_Start_InFrame 18
De_novo_Start_OutOfFrame 55
Frame_Shift_Del 1569
Frame_Shift_Ins 489
In_Frame_Del 624
In_Frame_Ins 46
Missense_Mutation 35748
Nonsense_Mutation 2173
Nonstop_Mutation 28
Silent 13644
Splice_Site 2035
Start_Codon_Del 5
Start_Codon_Ins 1
Start_Codon_SNP 47
Total 56482
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 12950 1305636481 9.9e-06 9.9 5.4 2.1
*Cp(A/C/T)->T 6997 10679844101 6.6e-07 0.66 0.36 1.7
A->G 5013 11517036264 4.4e-07 0.44 0.24 2.3
transver 10835 23502516846 4.6e-07 0.46 0.25 5
indel+null 6875 23502516846 2.9e-07 0.29 0.16 NaN
double_null 167 23502516846 7.1e-09 0.0071 0.0039 NaN
Total 42837 23502516846 1.8e-06 1.8 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: GBMLGG-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: 116. 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 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 2607867 83 75 48 0 6 20 23 15 19 0 <1.00e-15 1.69e-10 0.0023 0.004 0.00036 <0.000 <0.000
2 ATRX alpha thalassemia/mental retardation syndrome X-linked (RAD54 homolog, S. cerevisiae) 5992783 215 206 186 9 3 4 18 12 167 11 <1.00e-15 4.83e-05 0.0027 0.22 0.0052 <2.22e-16 <1.21e-12
3 IDH1 isocitrate dehydrogenase 1 (NADP+), soluble 1011466 412 412 2 0 391 0 0 21 0 0 1.67e-15 <1.00e-15 0 1 0 <1.00e-15 <1.21e-12
4 TP53 tumor protein p53 988411 409 328 162 2 136 45 58 86 77 7 1.22e-15 <1.00e-15 0 0 0 <1.00e-15 <1.21e-12
5 CIC capicua homolog (Drosophila) 3432130 119 109 84 1 41 5 6 14 47 6 2.89e-15 8.31e-12 0 0.022 0 <1.00e-15 <1.21e-12
6 EGFR epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian) 3153012 137 109 62 8 16 58 4 51 8 0 <1.00e-15 1.36e-13 0 0 0 <1.00e-15 <1.21e-12
7 PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (alpha) 1880697 56 54 40 2 1 5 8 7 34 1 5.66e-15 0.00946 0 0.46 0 <1.00e-15 <1.21e-12
8 NOTCH1 Notch homolog 1, translocation-associated (Drosophila) 4913138 52 42 40 3 4 8 2 11 24 3 3.55e-15 0.00226 0 0.067 0 <1.00e-15 <1.21e-12
9 IDH2 isocitrate dehydrogenase 2 (NADP+), mitochondrial 927564 20 20 3 0 0 12 2 6 0 0 1.02e-14 0.000138 0 1 0 <1.00e-15 <1.21e-12
10 ZNF709 zinc finger protein 709 1544395 6 6 2 0 0 6 0 0 0 0 0.00231 0.175 0 0.88 0 <1.00e-15 <1.21e-12
11 PRCP prolylcarboxypeptidase (angiotensinase C) 1260840 5 5 5 0 1 1 1 0 2 0 0.0145 0.154 0.21 0 0 <1.00e-15 <1.21e-12
12 NCK1 NCK adaptor protein 1 911271 2 2 2 0 0 0 0 0 2 0 0.311 0.592 1 0 0 <1.00e-15 <1.21e-12
13 OPRK1 opioid receptor, kappa 1 874196 2 2 2 1 0 0 1 0 1 0 0.261 0.768 0.56 0 0 <1.00e-15 <1.21e-12
14 PIPOX pipecolic acid oxidase 959164 2 2 2 0 0 0 0 1 1 0 0.429 0.601 0.48 0 0 <1.00e-15 <1.21e-12
15 TEAD3 TEA domain family member 3 959075 2 2 2 1 0 1 0 0 1 0 0.477 0.670 0.052 0 0 <1.00e-15 <1.21e-12
16 RB1 retinoblastoma 1 (including osteosarcoma) 2093885 30 30 27 1 0 0 1 0 28 1 4.00e-15 0.0475 0.03 0.025 0.013 2.00e-15 2.26e-12
17 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 951867 114 111 89 0 6 24 14 18 52 0 3.66e-15 7.96e-12 0.013 0.44 0.032 4.44e-15 4.73e-12
18 NF1 neurofibromin 1 (neurofibromatosis, von Recklinghausen disease, Watson disease) 6890964 68 62 66 3 0 6 3 6 37 16 6.44e-15 0.000393 0.094 0.96 0.19 4.32e-14 4.35e-11
19 FUBP1 far upstream element (FUSE) binding protein 1 1584099 49 48 44 1 0 0 1 1 45 2 5.44e-15 0.0394 0.21 0.99 0.36 6.88e-14 6.56e-11
20 TCF12 transcription factor 12 (HTF4, helix-loop-helix transcription factors 4) 1804810 20 19 18 0 0 0 0 1 18 1 1.93e-13 0.621 0.057 0.1 0.043 2.79e-13 2.53e-10
21 ZBTB20 zinc finger and BTB domain containing 20 1619806 23 22 20 3 4 1 6 4 8 0 6.57e-11 0.137 0.0017 0.044 0.0005 1.06e-12 9.16e-10
22 KEL Kell blood group, metallo-endopeptidase 1770085 25 24 22 2 12 1 0 6 6 0 1.25e-13 0.0267 0.68 0.93 0.81 3.13e-12 2.58e-09
23 STK19 serine/threonine kinase 19 864334 12 11 4 0 0 0 2 1 9 0 1.28e-07 0.418 0.000041 0.7 0.00012 3.96e-10 3.12e-07
24 TPTE2 transmembrane phosphoinositide 3-phosphatase and tensin homolog 2 1293092 13 13 10 0 3 0 2 2 6 0 4.98e-09 0.0135 0.013 0.26 0.025 2.93e-09 2.21e-06
25 BRAF v-raf murine sarcoma viral oncogene homolog B1 1775176 12 11 6 1 1 1 1 8 1 0 9.17e-06 0.279 0.000039 0.046 0.000036 7.58e-09 5.49e-06
26 GABRA6 gamma-aminobutyric acid (GABA) A receptor, alpha 6 1112173 15 15 12 2 6 2 1 5 1 0 6.06e-10 0.0992 0.77 0.68 0.86 1.16e-08 8.10e-06
27 CDH18 cadherin 18, type 2 1921544 16 16 15 0 3 4 2 6 1 0 1.06e-08 0.0105 0.073 0.81 0.12 2.75e-08 1.85e-05
28 EMG1 EMG1 nucleolar protein homolog (S. cerevisiae) 559498 6 6 2 0 0 0 0 0 6 0 2.70e-05 1.000 2e-06 0.99 0.000075 4.28e-08 2.77e-05
29 OR8K3 olfactory receptor, family 8, subfamily K, member 3 746739 10 10 10 1 2 3 0 3 2 0 6.79e-09 0.144 0.73 0.92 0.87 1.18e-07 7.34e-05
30 CREBZF CREB/ATF bZIP transcription factor 834352 9 9 3 0 0 0 0 2 7 0 3.45e-05 0.638 0.00015 0.19 0.00035 2.30e-07 0.000139
31 RPL5 ribosomal protein L5 733819 10 10 10 0 0 2 1 2 5 0 6.81e-08 0.136 0.15 0.2 0.2 2.54e-07 0.000144
32 KRT15 keratin 15 1116447 8 8 6 1 8 0 0 0 0 0 0.000156 0.192 0.000049 0.82 0.000085 2.55e-07 0.000144
33 SPTA1 spectrin, alpha, erythrocytic 1 (elliptocytosis 2) 5939665 34 30 33 2 16 2 1 11 3 1 6.68e-08 0.0214 0.19 0.29 0.21 2.67e-07 0.000147
34 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 551830 5 4 3 1 0 2 1 2 0 0 0.000995 0.555 0.000059 0.025 0.000032 5.85e-07 0.000307
35 SMARCA4 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4 3632457 29 27 26 6 8 2 4 9 6 0 0.000130 0.232 0.00018 0.1 0.00025 5.93e-07 0.000307
PIK3CA

Figure S1.  This figure depicts the distribution of mutations and mutation types across the PIK3CA significant gene.

ATRX

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

IDH1

Figure S3.  This figure depicts the distribution of mutations and mutation types across the IDH1 significant gene.

TP53

Figure S4.  This figure depicts the distribution of mutations and mutation types across the TP53 significant gene.

CIC

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

EGFR

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

PIK3R1

Figure S7.  This figure depicts the distribution of mutations and mutation types across the PIK3R1 significant gene.

NOTCH1

Figure S8.  This figure depicts the distribution of mutations and mutation types across the NOTCH1 significant gene.

IDH2

Figure S9.  This figure depicts the distribution of mutations and mutation types across the IDH2 significant gene.

ZNF709

Figure S10.  This figure depicts the distribution of mutations and mutation types across the ZNF709 significant gene.

PRCP

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

NCK1

Figure S12.  This figure depicts the distribution of mutations and mutation types across the NCK1 significant gene.

OPRK1

Figure S13.  This figure depicts the distribution of mutations and mutation types across the OPRK1 significant gene.

PIPOX

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

TEAD3

Figure S15.  This figure depicts the distribution of mutations and mutation types across the TEAD3 significant gene.

RB1

Figure S16.  This figure depicts the distribution of mutations and mutation types across the RB1 significant gene.

PTEN

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

NF1

Figure S18.  This figure depicts the distribution of mutations and mutation types across the NF1 significant gene.

FUBP1

Figure S19.  This figure depicts the distribution of mutations and mutation types across the FUBP1 significant gene.

TCF12

Figure S20.  This figure depicts the distribution of mutations and mutation types across the TCF12 significant gene.

ZBTB20

Figure S21.  This figure depicts the distribution of mutations and mutation types across the ZBTB20 significant gene.

KEL

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

STK19

Figure S23.  This figure depicts the distribution of mutations and mutation types across the STK19 significant gene.

TPTE2

Figure S24.  This figure depicts the distribution of mutations and mutation types across the TPTE2 significant gene.

BRAF

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

GABRA6

Figure S26.  This figure depicts the distribution of mutations and mutation types across the GABRA6 significant gene.

CDH18

Figure S27.  This figure depicts the distribution of mutations and mutation types across the CDH18 significant gene.

OR8K3

Figure S28.  This figure depicts the distribution of mutations and mutation types across the OR8K3 significant gene.

CREBZF

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

RPL5

Figure S30.  This figure depicts the distribution of mutations and mutation types across the RPL5 significant gene.

KRT15

Figure S31.  This figure depicts the distribution of mutations and mutation types across the KRT15 significant gene.

SPTA1

Figure S32.  This figure depicts the distribution of mutations and mutation types across the SPTA1 significant gene.

KRAS

Figure S33.  This figure depicts the distribution of mutations and mutation types across the KRAS 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: 72. 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 412 5 412 3980 614704 0 0
2 IDH2 isocitrate dehydrogenase 2 (NADP+), mitochondrial 20 6 20 4776 1660 0 0
3 TP53 tumor protein p53 409 356 394 283376 129979 0 0
4 PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (alpha) 56 33 26 26268 47 0 0
5 EGFR epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian) 137 293 101 233228 1581 0 0
6 PTPN11 protein tyrosine phosphatase, non-receptor type 11 (Noonan syndrome 1) 11 32 10 25472 254 0 0
7 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 83 220 68 175120 15918 0 0
8 SMARCA4 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4 29 30 7 23880 4 0 0
9 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 114 767 111 610532 3746 0 0
10 PDGFRA platelet-derived growth factor receptor, alpha polypeptide 31 69 8 54924 15 0 0

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: 105. 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 HSA04210_APOPTOSIS Genes involved in apoptosis AIFM1, AKT1, AKT2, AKT3, APAF1, ATM, BAD, BAX, BCL2, BCL2L1, BID, BIRC2, BIRC3, BIRC4, CAPN1, CAPN2, CASP10, CASP3, CASP6, CASP7, CASP8, CASP9, CFLAR, CHP, CHUK, CSF2RB, CYCS, DFFA, DFFB, ENDOG, FADD, FAS, FASLG, IKBKB, IKBKG, IL1A, IL1B, IL1R1, IL1RAP, IL3, IL3RA, IRAK1, IRAK2, IRAK3, IRAK4, MAP3K14, MYD88, NFKB1, NFKB2, NFKBIA, NGFB, NTRK1, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRKACA, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, RELA, RIPK1, TNF, TNFRSF10A, TNFRSF10B, TNFRSF10C, TNFRSF10D, TNFRSF1A, TNFSF10, TP53, TRADD, TRAF2 80 AIFM1(6), AKT1(2), APAF1(3), ATM(12), BAX(1), BCL2(2), BIRC2(3), BIRC3(1), CAPN1(2), CASP10(1), CASP8(2), CASP9(1), CFLAR(1), CHUK(1), CSF2RB(6), CYCS(2), DFFA(2), FAS(1), FASLG(1), IKBKB(2), IL1A(1), IL1B(3), IL1R1(4), IL1RAP(2), IL3(2), IL3RA(4), IRAK1(3), IRAK2(3), IRAK3(9), IRAK4(2), NFKB1(2), NFKB2(2), NFKBIA(3), NTRK1(3), PIK3CA(83), PIK3CB(7), PIK3CD(3), PIK3CG(12), PIK3R1(56), PIK3R2(4), PIK3R3(2), PIK3R5(4), PPP3CA(1), PPP3CB(1), PPP3CC(1), PRKACG(1), PRKAR1A(2), PRKAR1B(1), PRKAR2B(1), RELA(1), RIPK1(4), TNF(1), TNFRSF10C(1), TNFRSF10D(1), TNFRSF1A(1), TNFSF10(2), TP53(409), TRADD(1), TRAF2(2) 99368867 697 465 398 56 182 95 106 148 158 8 <1.00e-15 <1.00e-15 <2.57e-14
2 HSA00020_CITRATE_CYCLE Genes involved in citrate cycle (TCA cycle) ACLY, ACO1, ACO2, CLYBL, CS, DLD, DLST, FH, IDH1, IDH2, IDH3A, IDH3B, IDH3G, LOC283398, LOC441996, MDH1, MDH2, OGDH, OGDHL, PC, PCK1, PCK2, SDHA, SDHB, SDHC, SDHD, SUCLA2, SUCLG1, SUCLG2 27 ACLY(4), ACO1(6), ACO2(4), CLYBL(5), DLD(3), FH(1), IDH1(412), IDH2(20), IDH3A(1), IDH3B(1), OGDH(1), OGDHL(7), PC(4), PCK1(6), SDHA(4), SDHC(2), SUCLA2(1), SUCLG1(2), SUCLG2(1) 35404065 485 451 57 15 404 22 10 43 6 0 <1.00e-15 <1.00e-15 <2.57e-14
3 HSA00480_GLUTATHIONE_METABOLISM Genes involved in glutathione metabolism ANPEP, G6PD, GCLC, GCLM, GGT1, GGTL3, GGTL4, GPX1, GPX2, GPX3, GPX4, GPX5, GPX6, GPX7, GSR, GSS, GSTA1, GSTA2, GSTA3, GSTA4, GSTA5, GSTK1, GSTM1, GSTM2, GSTM3, GSTM4, GSTM5, GSTO2, GSTP1, GSTT1, GSTT2, GSTZ1, IDH1, IDH2, MGST1, MGST2, MGST3, OPLAH, TXNDC12 36 ANPEP(5), G6PD(3), GCLC(1), GGT1(3), GPX2(2), GPX5(1), GPX6(1), GSS(2), GSTA1(3), GSTA2(1), GSTA3(1), GSTA4(3), GSTA5(4), GSTK1(2), GSTM4(1), GSTM5(1), GSTT1(1), GSTZ1(3), IDH1(412), IDH2(20), OPLAH(3) 26139528 473 449 46 14 404 24 8 33 4 0 <1.00e-15 <1.00e-15 <2.57e-14
4 TELPATHWAY Telomerase is a ribonucleotide protein that adds telomeric repeats to the 3' ends of chromosomes. AKT1, BCL2, EGFR, G22P1, HSPCA, IGF1R, KRAS2, MYC, POLR2A, PPP2CA, PRKCA, RB1, TEP1, TERF1, TERT, TNKS, TP53, XRCC5 15 AKT1(2), BCL2(2), EGFR(137), IGF1R(10), POLR2A(9), PPP2CA(4), PRKCA(6), RB1(30), TEP1(12), TERF1(1), TERT(5), TNKS(2), TP53(409), XRCC5(4) 33523326 633 448 308 24 172 108 72 151 121 9 <1.00e-15 <1.00e-15 <2.57e-14
5 CITRATE_CYCLE_TCA_CYCLE ACO1, ACO2, CS, DLD, DLST, DLSTP, FH, IDH1, IDH2, IDH3A, IDH3B, IDH3G, MDH1, MDH2, PC, PCK1, SDHA, SDHA, SDHAL2, SDHB, SUCLA2, SUCLG1, SUCLG2 20 ACO1(6), ACO2(4), DLD(3), FH(1), IDH1(412), IDH2(20), IDH3A(1), IDH3B(1), PC(4), PCK1(6), SDHA(4), SUCLA2(1), SUCLG1(2), SUCLG2(1) 24437050 466 444 38 5 399 21 7 36 3 0 <1.00e-15 <1.00e-15 <2.57e-14
6 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(6), CDKN2A(6), E2F1(1), MDM2(5), PIK3CA(83), PIK3R1(56), POLR1A(7), POLR1B(3), RAC1(1), RB1(30), TBX2(1), TP53(409) 24072269 608 439 306 13 150 73 94 115 167 9 <1.00e-15 <1.00e-15 <2.57e-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(6), ATM(12), BUB1(5), BUB1B(2), BUB3(3), CCNA1(3), CCNA2(1), CCNB1(2), CCNB2(1), CCNB3(6), CCND2(2), CCND3(1), CCNE1(2), CCNE2(2), CCNH(2), CDAN1(5), CDC14A(2), CDC14B(5), CDC20(1), CDC25A(1), CDC25B(1), CDC6(1), CDC7(2), CDH1(4), CDK2(1), CDK4(1), CDKN1A(2), CDKN2A(6), CHEK1(6), CHEK2(3), DTX4(4), E2F1(1), E2F2(1), E2F3(1), E2F4(1), E2F5(1), E2F6(1), EP300(6), ESPL1(8), GSK3B(1), HDAC2(7), HDAC3(1), HDAC4(4), HDAC5(1), HDAC6(4), MAD1L1(1), MCM2(1), MCM3(3), MCM4(5), MCM5(3), MCM6(6), MCM7(6), MDM2(5), MPEG1(3), MPL(5), PLK1(2), PRKDC(14), PTPRA(7), RB1(30), RBL1(6), SKP2(3), SMAD4(1), TBC1D8(4), TFDP1(1), TP53(409), WEE1(2) 130682876 650 409 399 70 180 86 83 148 142 11 <1.00e-15 <1.00e-15 <2.57e-14
8 G1_TO_S_CELL_CYCLE_REACTOME ATM, CCNA1, CCNB1, CCND1, CCND2, CCND3, CCNE1, CCNE2, CCNG2, CCNH, CDC25A, CDC45L, CDK2, CDK4, CDK7, CDKN1A, CDKN1B, CDKN1C, CDKN2A, CDKN2B, CDKN2C, CDKN2D, CREB3, CREB3L1, CREB3L3, CREB3L4, CREBL1, CREBL1, TNXB, E2F1, E2F2, E2F3, E2F4, E2F5, E2F6, FLJ14001, GADD45A, GBA2, MCM2, MCM3, MCM4, MCM5, MCM6, MCM7, MDM2, MNAT1, MYC, MYT1, NACA, NACA, FKSG17, ORC1L, ORC2L, ORC3L, ORC4L, ORC5L, ORC6L, PCNA, POLA2, POLE, POLE2, PRIM1, PRIM2A, RB1, RBL1, RPA1, RPA2, RPA3, TFDP1, TFDP2, TP53, WEE1 64 ATM(12), CCNA1(3), CCNB1(2), CCND1(4), CCND2(2), CCND3(1), CCNE1(2), CCNE2(2), CCNG2(2), CCNH(2), CDC25A(1), CDK2(1), CDK4(1), CDK7(1), CDKN1A(2), CDKN1B(4), CDKN2A(6), CDKN2B(2), CDKN2C(6), CREB3L1(2), CREB3L3(3), CREB3L4(1), E2F1(1), E2F2(1), E2F3(1), E2F4(1), E2F5(1), E2F6(1), GBA2(1), MCM2(1), MCM3(3), MCM4(5), MCM5(3), MCM6(6), MCM7(6), MDM2(5), MYT1(7), NACA(6), POLA2(2), POLE(8), POLE2(1), PRIM1(2), RB1(30), RBL1(6), RPA1(3), RPA2(1), TFDP1(1), TNXB(14), TP53(409), WEE1(2) 91696536 590 397 339 45 162 62 81 128 149 8 <1.00e-15 <1.00e-15 <2.57e-14
9 APOPTOSIS APAF1, BAD, BAK1, BCL2L7P1, BAX, BCL2, BCL2L1, BCL2L11, BID, BIRC2, BIRC3, BIRC4, BIRC5, BNIP3L, CASP1, CASP10, CASP1, COPl, CASP2, CASP3, CASP4, CASP6, CASP7, CASP8, CASP9, CHUK, CYCS, DFFA, DFFB, FADD, FAS, FASLG, GZMB, HELLS, HRK, IKBKB, IKBKG, IRF1, IRF2, IRF3, IRF4, IRF5, IRF6, IRF7, JUN, LTA, MAP2K4, MAP3K1, MAPK10, MDM2, MYC, NFKB1, NFKBIA, NFKBIB, NFKBIE, PRF1, RELA, RIPK1, TNF, TNFRSF10B, TNFRSF1A, TNFRSF1B, TNFRSF21, TNFRSF25, TNFRSF25, PLEKHG5, TNFSF10, TP53, TP73, TRADD, TRAF1, TRAF2, TRAF3 66 APAF1(3), BAK1(2), BAX(1), BCL2(2), BCL2L11(1), BIRC2(3), BIRC3(1), CASP1(6), CASP10(1), CASP2(1), CASP4(1), CASP8(2), CASP9(1), CHUK(1), CYCS(2), DFFA(2), FAS(1), FASLG(1), GZMB(3), HELLS(3), IKBKB(2), IRF1(5), IRF2(2), IRF3(1), IRF4(4), IRF5(2), IRF6(4), IRF7(3), MAP3K1(9), MAPK10(1), MDM2(5), NFKB1(2), NFKBIA(3), NFKBIE(3), PLEKHG5(4), PRF1(3), RELA(1), RIPK1(4), TNF(1), TNFRSF1A(1), TNFRSF1B(3), TNFRSF21(2), TNFRSF25(2), TNFSF10(2), TP53(409), TRADD(1), TRAF1(1), TRAF2(2), TRAF3(1) 68081193 521 370 272 41 174 65 67 112 96 7 <1.00e-15 <1.00e-15 <2.57e-14
10 G1PATHWAY CDK4/6-cyclin D and CDK2-cyclin E phosphorylate Rb, which allows the transcription of genes needed for the G1/S cell cycle transition. ABL1, ATM, ATR, CCNA1, CCND1, CCNE1, CDC2, CDC25A, CDK2, CDK4, CDK6, CDKN1A, CDKN1B, CDKN2A, CDKN2B, DHFR, E2F1, GSK3B, HDAC1, MADH3, MADH4, RB1, SKP2, TFDP1, TGFB1, TGFB2, TGFB3, TP53 25 ABL1(6), ATM(12), ATR(10), CCNA1(3), CCND1(4), CCNE1(2), CDC25A(1), CDK2(1), CDK4(1), CDKN1A(2), CDKN1B(4), CDKN2A(6), CDKN2B(2), DHFR(1), E2F1(1), GSK3B(1), RB1(30), SKP2(3), TFDP1(1), TGFB2(2), TGFB3(1), TP53(409) 35802895 503 366 252 12 147 53 70 105 120 8 <1.00e-15 <1.00e-15 <2.57e-14

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 SA_REG_CASCADE_OF_CYCLIN_EXPR Expression of cyclins regulates progression through the cell cycle by activating cyclin-dependent kinases. CCNA1, CCNA2, CCND1, CCNE1, CCNE2, CDK2, CDK4, CDKN1B, CDKN2A, E2F1, E2F2, E2F4, PRB1 13 CCNA1(3), CCNA2(1), CCND1(4), CCNE1(2), CCNE2(2), CDK2(1), CDK4(1), CDKN1B(4), CDKN2A(6), E2F1(1), E2F2(1), E2F4(1), PRB1(2) 10572211 29 25 28 0 5 1 6 7 10 0 0.00029 0.0065 1
2 HSA00902_MONOTERPENOID_BIOSYNTHESIS Genes involved in monoterpenoid biosynthesis CYP2C19, CYP2C9 2 CYP2C19(5), CYP2C9(3) 2399460 8 8 8 0 4 2 0 1 1 0 0.1 0.0099 1
3 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 14 ARF1(1), CCND1(4), CDK2(1), CDK4(1), CDKN1A(2), CDKN1B(4), CDKN2A(6), CFL1(1), E2F1(1), E2F2(1), MDM2(5), PRB1(2) 8951305 29 24 28 3 6 2 5 5 11 0 0.019 0.029 1
4 HSA00472_D_ARGININE_AND_D_ORNITHINE_METABOLISM Genes involved in D-arginine and D-ornithine metabolism DAO 1 DAO(3) 854859 3 3 3 1 2 1 0 0 0 0 0.56 0.1 1
5 TCRMOLECULE T Cell Receptor and CD3 Complex CD3D, CD3E, CD3G, CD3Z, TRA@, TRB@ 3 CD3D(1), CD3E(2), CD3G(1) 1351852 4 4 4 1 0 1 1 1 1 0 0.57 0.11 1
6 BBCELLPATHWAY Fas ligand expression by T cells induces apoptosis in Fas-expressing, inactive B cells. CD28, CD4, HLA-DRA, HLA-DRB1, TNFRSF5, TNFRSF6, TNFSF5, TNFSF6 4 CD28(2), CD4(2), HLA-DRA(4), HLA-DRB1(1) 2824898 9 7 8 1 4 1 0 3 1 0 0.16 0.17 1
7 HSA00643_STYRENE_DEGRADATION Genes involved in styrene degradation FAH, GSTZ1, HGD 3 FAH(2), GSTZ1(3), HGD(5) 2645677 10 6 10 2 4 0 1 2 3 0 0.31 0.18 1
8 RIBOFLAVIN_METABOLISM ACP1, ACP2, ACP5, ACPP, ACPT, ENPP1, ENPP3, FLAD1, RFK, TYR 10 ACP1(1), ACPP(4), ACPT(2), ENPP1(5), ENPP3(2), FLAD1(2), TYR(5) 11508628 21 18 21 1 8 2 3 6 2 0 0.014 0.18 1
9 IL18PATHWAY Pro-inflammatory IL-18 is activated in macrophages by caspase-1 cleavage and, in conjunction with IL-12, stimulates Th1 cell differentiation. CASP1, IFNG, IL12A, IL12B, IL18, IL2 6 CASP1(6), IFNG(2), IL12B(4), IL18(3) 3542953 15 11 15 3 4 2 2 5 2 0 0.25 0.19 1
10 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 CCL11(2), CCL5(1), CCR3(2), CSF2(2), HLA-DRA(4), HLA-DRB1(1), IL3(2), IL5(1) 3611520 15 11 15 3 4 3 1 4 3 0 0.23 0.22 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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