Mutation Analysis (MutSig v2.0)
Glioma (Primary solid tumor)
28 January 2016  |  analyses__2016_01_28
Maintainer Information
Citation Information
doi:10.7908/C1057F9V
Maintained by David Heiman (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2016): Mutation Analysis (MutSig v2.0). Broad Institute of MIT and Harvard. doi:10.7908/C1057F9V
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: 799

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: 1410

  • Significantly mutated genes in COSMIC territory: 72

  • Significantly mutated genesets: 104

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

Mutation Preprocessing

  • Read 799 MAFs of type "maf1"

  • Total number of mutations in input MAFs: 67608

  • After removing 17 mutations outside chr1-24: 67591

  • After removing 3753 blacklisted mutations: 63838

  • After removing 3217 noncoding mutations: 60621

Mutation Filtering

  • Number of mutations before filtering: 60621

  • After removing 3086 mutations outside gene set: 57535

  • After removing 194 mutations outside category set: 57341

  • After removing 2 "impossible" mutations in

  • gene-patient-category bins of zero coverage: 54059

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 57
Frame_Shift_Del 1574
Frame_Shift_Ins 491
In_Frame_Del 624
In_Frame_Ins 47
Missense_Mutation 36312
Nonsense_Mutation 2202
Nonstop_Mutation 28
Silent 13870
Splice_Site 2065
Start_Codon_Del 5
Start_Codon_Ins 1
Start_Codon_SNP 47
Total 57341
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 13106 1310350025 1e-05 10 5.4 2.1
*Cp(A/C/T)->T 7102 10719143908 6.6e-07 0.66 0.36 1.7
A->G 5103 11559767602 4.4e-07 0.44 0.24 2.3
transver 11048 23589261535 4.7e-07 0.47 0.25 5
indel+null 6939 23589261535 2.9e-07 0.29 0.16 NaN
double_null 172 23589261535 7.3e-09 0.0073 0.004 NaN
Total 43470 23589261535 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 2617724 83 75 48 0 6 20 23 15 19 0 2.89e-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) 6015308 218 209 188 9 3 4 18 12 169 12 <1.00e-15 4.83e-05 0.0035 0.24 0.0048 <2.22e-16 <1.29e-12
3 IDH1 isocitrate dehydrogenase 1 (NADP+), soluble 1015291 415 415 2 0 394 0 0 21 0 0 1.11e-15 <1.00e-15 0 1 0 <1.00e-15 <1.29e-12
4 TP53 tumor protein p53 992117 413 331 162 2 139 45 59 86 77 7 2.22e-15 <1.00e-15 0 0 0 <1.00e-15 <1.29e-12
5 CIC capicua homolog (Drosophila) 3444953 119 109 84 1 41 5 6 14 47 6 1.55e-15 8.31e-12 0 0.022 0 <1.00e-15 <1.29e-12
6 EGFR epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian) 3164527 137 109 62 8 16 58 4 51 8 0 6.55e-15 1.36e-13 0 0 0 <1.00e-15 <1.29e-12
7 PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (alpha) 1887792 56 54 40 2 1 5 8 7 34 1 <1.00e-15 0.00946 0 0.46 0 <1.00e-15 <1.29e-12
8 NOTCH1 Notch homolog 1, translocation-associated (Drosophila) 4928959 52 42 40 3 4 8 2 11 24 3 8.55e-15 0.00226 0 0.056 0 <1.00e-15 <1.29e-12
9 IDH2 isocitrate dehydrogenase 2 (NADP+), mitochondrial 931063 20 20 3 0 0 12 2 6 0 0 <1.00e-15 0.000138 0 1 0 <1.00e-15 <1.29e-12
10 PRCP prolylcarboxypeptidase (angiotensinase C) 1265587 5 5 5 0 1 1 1 0 2 0 0.0150 0.154 0.21 0 0 <1.00e-15 <1.29e-12
11 NCK1 NCK adaptor protein 1 914709 2 2 2 0 0 0 0 0 2 0 0.316 0.592 1 0 0 <1.00e-15 <1.29e-12
12 OPRK1 opioid receptor, kappa 1 877529 2 2 2 1 0 0 1 0 1 0 0.266 0.768 0.56 0 0 <1.00e-15 <1.29e-12
13 PIPOX pipecolic acid oxidase 962779 2 2 2 0 0 0 0 1 1 0 0.435 0.601 0.48 0 0 <1.00e-15 <1.29e-12
14 TNFRSF19 tumor necrosis factor receptor superfamily, member 19 1025436 2 2 2 0 1 0 0 0 1 0 0.347 0.368 0.062 0.54 0 <1.00e-15 <1.29e-12
15 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 955569 114 111 89 0 6 24 14 18 52 0 5.77e-15 7.96e-12 0.013 0.44 0.032 6.99e-15 8.45e-12
16 RB1 retinoblastoma 1 (including osteosarcoma) 2101716 31 30 28 1 0 0 2 0 28 1 9.44e-15 0.0328 0.052 0.028 0.022 7.66e-15 8.67e-12
17 NF1 neurofibromin 1 (neurofibromatosis, von Recklinghausen disease, Watson disease) 6916882 68 62 66 4 0 6 3 6 37 16 2.78e-15 0.00142 0.093 0.96 0.19 1.91e-14 2.03e-11
18 FUBP1 far upstream element (FUSE) binding protein 1 1590133 49 48 44 1 0 0 1 1 45 2 4.44e-15 0.0394 0.21 0.99 0.36 5.65e-14 5.69e-11
19 TCF12 transcription factor 12 (HTF4, helix-loop-helix transcription factors 4) 1811604 20 19 18 0 0 0 0 1 18 1 2.60e-13 0.621 0.057 0.1 0.043 3.73e-13 3.55e-10
20 ZBTB20 zinc finger and BTB domain containing 20 1625911 23 22 20 3 4 1 6 4 8 0 7.89e-11 0.137 0.0017 0.044 0.0005 1.27e-12 1.15e-09
21 KEL Kell blood group, metallo-endopeptidase 1776674 25 24 22 2 12 1 0 6 6 0 1.50e-13 0.0267 0.68 0.93 0.81 3.74e-12 3.23e-09
22 STK19 serine/threonine kinase 19 867586 12 11 4 0 0 0 2 1 9 0 1.51e-07 0.418 0.000041 0.7 0.00012 4.65e-10 3.83e-07
23 TPTE2 transmembrane phosphoinositide 3-phosphatase and tensin homolog 2 1298027 13 13 10 0 3 0 2 2 6 0 5.88e-09 0.0135 0.013 0.26 0.025 3.44e-09 2.71e-06
24 BRAF v-raf murine sarcoma viral oncogene homolog B1 1781869 12 11 6 1 1 1 1 8 1 0 9.89e-06 0.279 0.000039 0.046 0.000036 8.14e-09 6.14e-06
25 GABRA6 gamma-aminobutyric acid (GABA) A receptor, alpha 6 1116367 15 15 12 2 6 2 1 5 1 0 7.22e-10 0.0992 0.77 0.68 0.86 1.37e-08 9.95e-06
26 CDH18 cadherin 18, type 2 1928792 16 16 15 0 3 4 2 6 1 0 1.31e-08 0.0105 0.073 0.81 0.12 3.38e-08 2.35e-05
27 OR8K3 olfactory receptor, family 8, subfamily K, member 3 749546 10 10 10 1 2 3 0 3 2 0 7.40e-09 0.144 0.73 0.92 0.87 1.28e-07 8.56e-05
28 KRT15 keratin 15 1120656 8 8 6 1 8 0 0 0 0 0 0.000167 0.192 0.000049 0.82 0.000085 2.72e-07 0.000170
29 CREBZF CREB/ATF bZIP transcription factor 837481 9 9 3 0 0 0 0 2 7 0 4.11e-05 0.638 0.00015 0.19 0.00035 2.72e-07 0.000170
30 RPL5 ribosomal protein L5 736595 10 10 10 0 0 2 1 2 5 0 7.66e-08 0.136 0.15 0.2 0.2 2.84e-07 0.000171
31 SPTA1 spectrin, alpha, erythrocytic 1 (elliptocytosis 2) 5962069 35 30 34 2 16 2 1 12 3 1 7.91e-08 0.0191 0.22 0.23 0.24 3.61e-07 0.000211
32 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 553884 5 4 3 1 0 2 1 2 0 0 0.00104 0.555 0.000059 0.025 0.000031 5.93e-07 0.000330
33 EMG1 EMG1 nucleolar protein homolog (S. cerevisiae) 561442 5 5 2 0 0 0 0 0 5 0 0.000246 1.000 0.000021 0.99 0.00013 6.02e-07 0.000330
34 OR4P4 olfactory receptor, family 4, subfamily P, member 4 687934 9 9 9 1 2 3 1 2 1 0 4.54e-08 0.176 0.61 0.79 0.87 7.13e-07 0.000380
35 SMARCA4 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4 3645265 29 27 26 6 8 2 4 9 6 0 0.000146 0.232 0.00018 0.1 0.00033 8.52e-07 0.000441
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.

PRCP

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

NCK1

Figure S11.  This figure depicts the distribution of mutations and mutation types across the NCK1 significant gene.

OPRK1

Figure S12.  This figure depicts the distribution of mutations and mutation types across the OPRK1 significant gene.

PIPOX

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

TNFRSF19

Figure S14.  This figure depicts the distribution of mutations and mutation types across the TNFRSF19 significant gene.

PTEN

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

RB1

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

NF1

Figure S17.  This figure depicts the distribution of mutations and mutation types across the NF1 significant gene.

FUBP1

Figure S18.  This figure depicts the distribution of mutations and mutation types across the FUBP1 significant gene.

TCF12

Figure S19.  This figure depicts the distribution of mutations and mutation types across the TCF12 significant gene.

ZBTB20

Figure S20.  This figure depicts the distribution of mutations and mutation types across the ZBTB20 significant gene.

KEL

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

STK19

Figure S22.  This figure depicts the distribution of mutations and mutation types across the STK19 significant gene.

TPTE2

Figure S23.  This figure depicts the distribution of mutations and mutation types across the TPTE2 significant gene.

BRAF

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

GABRA6

Figure S25.  This figure depicts the distribution of mutations and mutation types across the GABRA6 significant gene.

CDH18

Figure S26.  This figure depicts the distribution of mutations and mutation types across the CDH18 significant gene.

OR8K3

Figure S27.  This figure depicts the distribution of mutations and mutation types across the OR8K3 significant gene.

KRT15

Figure S28.  This figure depicts the distribution of mutations and mutation types across the KRT15 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.

SPTA1

Figure S31.  This figure depicts the distribution of mutations and mutation types across the SPTA1 significant gene.

KRAS

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

OR4P4

Figure S33.  This figure depicts the distribution of mutations and mutation types across the OR4P4 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 TP53 tumor protein p53 413 356 398 284444 132630 0 0
2 EGFR epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian) 137 293 101 234107 1581 0 0
3 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 83 220 68 175780 15918 0 0
4 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 114 767 111 612833 3746 0 0
5 RB1 retinoblastoma 1 (including osteosarcoma) 31 267 18 213333 45 0 0
6 NF1 neurofibromin 1 (neurofibromatosis, von Recklinghausen disease, Watson disease) 68 285 19 227715 47 0 0
7 IDH1 isocitrate dehydrogenase 1 (NADP+), soluble 415 5 415 3995 619180 4.5e-14 2.9e-11
8 IDH2 isocitrate dehydrogenase 2 (NADP+), mitochondrial 20 6 20 4794 1660 5.4e-14 3e-11
9 ATRX alpha thalassemia/mental retardation syndrome X-linked (RAD54 homolog, S. cerevisiae) 218 4 5 3196 5 9.4e-14 4.3e-11
10 FUBP1 far upstream element (FUSE) binding protein 1 49 4 5 3196 2 9.4e-14 4.3e-11

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: 104. 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(7), 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(3), 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(413), TRADD(1), TRAF2(2) 99735425 703 468 400 57 185 95 109 148 158 8 <1.00e-15 <1.00e-15 <2.80e-14
2 HSA04115_P53_SIGNALING_PATHWAY Genes involved in p53 signaling pathway APAF1, ATM, ATR, BAI1, BAX, BBC3, BID, CASP3, CASP8, CASP9, CCNB1, CCNB2, CCNB3, CCND1, CCND2, CCND3, CCNE1, CCNE2, CCNG1, CCNG2, CD82, CDC2, CDK2, CDK4, CDK6, CDKN1A, CDKN2A, CHEK1, CHEK2, CYCS, DDB2, EI24, FAS, GADD45A, GADD45B, GADD45G, GTSE1, IGF1, IGFBP3, LRDD, MDM2, MDM4, P53AIP1, PERP, PMAIP1, PPM1D, PTEN, RCHY1, RFWD2, RPRM, RRM2, RRM2B, SCOTIN, SERPINB5, SERPINE1, SESN1, SESN2, SESN3, SFN, SIAH1, STEAP3, THBS1, TNFRSF10B, TP53, TP53I3, TP73, TSC2, ZMAT3 64 APAF1(3), ATM(12), ATR(10), BAI1(5), BAX(1), CASP8(2), CASP9(1), CCNB1(2), CCNB2(1), CCNB3(6), CCND1(4), CCND2(2), CCND3(1), CCNE1(2), CCNE2(2), CCNG1(2), CCNG2(2), CDK2(1), CDK4(1), CDK6(1), CDKN1A(2), CDKN2A(6), CHEK1(6), CHEK2(3), CYCS(2), DDB2(3), EI24(4), FAS(1), GADD45B(1), GTSE1(5), IGF1(3), MDM2(5), MDM4(2), PPM1D(4), PTEN(114), RCHY1(1), RFWD2(4), RPRM(1), RRM2(1), RRM2B(1), SERPINB5(2), SERPINE1(4), SESN1(2), SESN2(1), SESN3(2), SFN(3), SIAH1(3), STEAP3(2), THBS1(6), TP53(413), TP53I3(1), TSC2(6), ZMAT3(3) 77810162 678 458 400 42 173 92 100 146 160 7 <1.00e-15 <1.00e-15 <2.80e-14
3 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(415), IDH2(20), IDH3A(1), IDH3B(1), OGDH(1), OGDHL(7), PC(4), PCK1(6), SDHA(4), SDHC(2), SUCLA2(1), SUCLG1(2), SUCLG2(1) 35536282 488 454 57 16 407 22 10 43 6 0 <1.00e-15 <1.00e-15 <2.80e-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(31), TEP1(12), TERF1(1), TERT(6), TNKS(2), TP53(413), XRCC5(4) 33647620 639 451 310 25 176 108 74 151 121 9 <1.00e-15 <1.00e-15 <2.80e-14
5 GLUTATHIONE_METABOLISM ANPEP, G6PD, GCLC, GCLM, GGT1, GPX1, GPX2, GPX3, GPX4, GPX5, GSS, GSTA1, GSTA2, GSTA3, GSTA4, GSTM1, GSTM2, GSTM3, GSTM4, GSTM5, GSTO2, GSTP1, GSTT1, GSTT2, GSTZ1, IDH1, IDH2, MGST1, MGST2, MGST3, PGD 30 ANPEP(5), G6PD(3), GCLC(1), GGT1(3), GPX2(2), GPX5(1), GSS(2), GSTA1(3), GSTA2(1), GSTA3(1), GSTA4(4), GSTM4(1), GSTM5(1), GSTT1(1), GSTZ1(3), IDH1(415), IDH2(20), PGD(1) 21545075 468 449 38 13 403 19 8 33 5 0 <1.00e-15 <1.00e-15 <2.80e-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(31), TBX2(1), TP53(413) 24162274 613 442 307 14 153 73 96 115 167 9 <1.00e-15 <1.00e-15 <2.80e-14
7 HSA00720_REDUCTIVE_CARBOXYLATE_CYCLE Genes involved in reductive carboxylate cycle (CO2 fixation) ACLY, ACO1, ACO2, ACSS1, ACSS2, FH, IDH1, IDH2, LOC441996, MDH1, MDH2, SUCLA2 11 ACLY(4), ACO1(6), ACO2(4), ACSS1(1), ACSS2(4), FH(1), IDH1(415), IDH2(20), SUCLA2(1) 15831885 456 441 26 1 400 17 4 31 4 0 <1.00e-15 <1.00e-15 <2.80e-14
8 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(9), GSK3B(1), HDAC2(7), HDAC3(1), HDAC4(4), HDAC5(1), HDAC6(4), MAD1L1(1), MCM2(2), MCM3(3), MCM4(5), MCM5(3), MCM6(6), MCM7(6), MDM2(5), MPEG1(3), MPL(5), PLK1(2), PRKDC(14), PTPRA(7), RB1(31), RBL1(6), SKP2(3), SMAD4(1), TBC1D8(4), TFDP1(1), TP53(413), WEE1(2) 131166249 657 412 402 71 183 88 85 148 142 11 <1.00e-15 <1.00e-15 <2.80e-14
9 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), CDK6(1), CDKN1A(2), CDKN1B(4), CDKN2A(6), CDKN2B(2), DHFR(1), E2F1(1), GSK3B(1), RB1(31), SKP2(3), TFDP1(1), TGFB2(2), TGFB3(1), TP53(413) 35937244 509 369 254 13 150 54 72 105 120 8 <1.00e-15 <1.00e-15 <2.80e-14
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(13), DAXX(5), PAX3(4), PML(3), RB1(31), SIRT1(1), SP100(6), TNF(1), TNFRSF1A(1), TNFRSF1B(3), TP53(413) 22771682 481 361 227 11 147 51 65 98 112 8 <1.00e-15 <1.00e-15 <2.80e-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) 10611291 29 25 28 0 5 1 6 7 10 0 0.00029 0.0074 1
2 HSA00902_MONOTERPENOID_BIOSYNTHESIS Genes involved in monoterpenoid biosynthesis CYP2C19, CYP2C9 2 CYP2C19(5), CYP2C9(3) 2408511 8 8 8 0 4 2 0 1 1 0 0.1 0.011 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) 8984687 29 24 28 3 6 2 5 5 11 0 0.019 0.032 1
4 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(7), IFNG(2), IL12B(4), IL18(3) 3556416 16 12 16 3 4 2 2 6 2 0 0.23 0.1 1
5 HSA00472_D_ARGININE_AND_D_ORNITHINE_METABOLISM Genes involved in D-arginine and D-ornithine metabolism DAO 1 DAO(3) 858097 3 3 3 1 2 1 0 0 0 0 0.56 0.1 1
6 TCRMOLECULE T Cell Receptor and CD3 Complex CD3D, CD3E, CD3G, CD3Z, TRA@, TRB@ 3 CD3D(1), CD3E(2), CD3G(1) 1356956 4 4 4 1 0 1 1 1 1 0 0.57 0.12 1
7 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) 2835540 9 7 8 1 4 1 0 3 1 0 0.16 0.17 1
8 HSA00643_STYRENE_DEGRADATION Genes involved in styrene degradation FAH, GSTZ1, HGD 3 FAH(2), GSTZ1(3), HGD(5) 2655605 10 6 10 2 4 0 1 2 3 0 0.31 0.18 1
9 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) 11551817 21 18 21 1 8 2 3 6 2 0 0.014 0.2 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) 3625072 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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