Mutation Analysis (MutSig v1.5)
Glioma (Primary solid tumor)
02 April 2015  |  analyses__2015_04_02
Maintainer Information
Citation Information
doi:10.7908/C1NS0SXH
Maintained by David Heiman (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2015): Mutation Analysis (MutSig v1.5). Broad Institute of MIT and Harvard. doi:10.7908/C1NS0SXH
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: 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): 147

  • Mutations seen in COSMIC: 1405

  • Significantly mutated genes in COSMIC territory: 72

  • Significantly mutated genesets: 104

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

Mutation Preprocessing

  • Read 796 MAFs of type "Broad"

  • Total number of mutations in input MAFs: 66605

  • After removing 17 mutations outside chr1-24: 66588

  • After removing 3696 blacklisted mutations: 62892

  • After removing 2020 noncoding mutations: 60872

Mutation Filtering

  • Number of mutations before filtering: 60872

  • After removing 2788 mutations outside gene set: 58084

  • After removing 188 mutations outside category set: 57896

  • After removing 2 "impossible" mutations in

  • gene-patient-category bins of zero coverage: 54918

Results
Breakdown of Mutations by Type

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

type count
Frame_Shift_Del 1627
Frame_Shift_Ins 507
In_Frame_Del 640
In_Frame_Ins 48
Missense_Mutation 36921
Nonsense_Mutation 2249
Nonstop_Mutation 32
Silent 13972
Splice_Site 1683
Translation_Start_Site 217
Total 57896
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 13446 1305636481 1e-05 10 5.5 2.1
*Cp(A/C/T)->T 7252 10679844101 6.8e-07 0.68 0.36 1.7
A->G 5198 11517036264 4.5e-07 0.45 0.24 2.3
transver 11229 23502516846 4.8e-07 0.48 0.26 5
indel+null 6631 23502516846 2.8e-07 0.28 0.15 NaN
double_null 167 23502516846 7.1e-09 0.0071 0.0038 NaN
Total 43923 23502516846 1.9e-06 1.9 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_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: 147. 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 IDH1 isocitrate dehydrogenase 1 (NADP+), soluble 1011466 412 412 2 0 391 0 0 21 0 0 <1.00e-15 <1.00e-15 <3.02e-12
2 TP53 tumor protein p53 988411 408 327 162 3 136 45 58 86 76 7 <1.00e-15 <1.00e-15 <3.02e-12
3 ATRX alpha thalassemia/mental retardation syndrome X-linked (RAD54 homolog, S. cerevisiae) 5992783 216 206 187 9 3 4 18 12 168 11 4.83e-05 <1.00e-15 <3.02e-12
4 CIC capicua homolog (Drosophila) 3432130 119 109 84 1 41 5 6 14 47 6 8.31e-12 <1.00e-15 <3.02e-12
5 EGFR epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian) 3153012 138 109 63 8 17 59 4 51 7 0 9.30e-14 <1.00e-15 <3.02e-12
6 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 2607867 83 75 48 0 6 21 23 15 18 0 1.69e-10 <1.00e-15 <3.02e-12
7 NOTCH1 Notch homolog 1, translocation-associated (Drosophila) 4913138 52 42 40 3 4 8 2 11 24 3 0.00226 3.55e-15 9.19e-12
8 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 951867 115 112 90 0 6 24 14 20 51 0 7.96e-12 4.55e-15 9.25e-12
9 RB1 retinoblastoma 1 (including osteosarcoma) 2093885 30 30 27 1 0 0 1 1 27 1 0.0475 4.88e-15 9.25e-12
10 NF1 neurofibromin 1 (neurofibromatosis, von Recklinghausen disease, Watson disease) 6890964 68 62 66 3 0 6 3 6 37 16 0.000393 5.11e-15 9.25e-12
11 FUBP1 far upstream element (FUSE) binding protein 1 1584099 49 48 44 1 0 0 1 1 45 2 0.0394 6.00e-15 9.87e-12
12 IDH2 isocitrate dehydrogenase 2 (NADP+), mitochondrial 927564 20 20 3 0 0 12 2 6 0 0 0.000138 8.88e-15 1.30e-11
13 PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (alpha) 1880697 56 54 40 2 1 5 8 7 34 1 0.00946 9.33e-15 1.30e-11
14 KEL Kell blood group, metallo-endopeptidase 1770085 25 24 22 2 12 1 1 6 5 0 0.0267 2.61e-13 3.29e-10
15 TCF12 transcription factor 12 (HTF4, helix-loop-helix transcription factors 4) 1804810 20 19 18 0 0 0 0 1 18 1 0.621 2.72e-13 3.29e-10
16 ZBTB20 zinc finger and BTB domain containing 20 1619806 23 22 20 3 4 1 6 4 8 0 0.137 1.00e-10 1.14e-07
17 GABRA6 gamma-aminobutyric acid (GABA) A receptor, alpha 6 1112173 15 15 12 2 6 3 1 5 0 0 0.0992 9.18e-10 9.78e-07
18 TPTE2 transmembrane phosphoinositide 3-phosphatase and tensin homolog 2 1293092 13 13 10 0 3 1 2 2 5 0 0.0135 6.59e-09 6.64e-06
19 OR8K3 olfactory receptor, family 8, subfamily K, member 3 746739 10 10 10 1 2 3 0 3 2 0 0.144 8.09e-09 7.72e-06
20 CDH18 cadherin 18, type 2 1921544 16 16 15 0 3 4 2 6 1 0 0.0105 1.59e-08 1.44e-05
21 OR4P4 olfactory receptor, family 4, subfamily P, member 4 685109 9 9 9 1 2 3 1 2 1 0 0.176 4.99e-08 4.31e-05
22 RPL5 ribosomal protein L5 733819 10 10 10 0 0 2 1 2 5 0 0.136 5.73e-08 4.72e-05
23 SEMG2 semenogelin II 1398493 13 13 10 2 9 1 2 0 1 0 0.176 7.62e-08 6.00e-05
24 SPTA1 spectrin, alpha, erythrocytic 1 (elliptocytosis 2) 5939665 34 30 33 2 16 2 1 11 3 1 0.0214 1.11e-07 8.35e-05
25 STK19 serine/threonine kinase 19 864334 12 11 4 0 0 0 2 1 9 0 0.418 1.69e-07 0.000123
26 KIF2B kinesin family member 2B 1612591 16 16 15 2 6 0 2 6 2 0 0.154 3.66e-07 0.000255
27 UGT2A3 UDP glucuronosyltransferase 2 family, polypeptide A3 1274621 12 11 12 0 1 2 4 4 1 0 0.0224 1.40e-06 0.000939
28 STAG2 stromal antigen 2 3103277 17 16 17 1 1 1 0 2 13 0 0.239 1.85e-06 0.00120
29 EMG1 EMG1 nucleolar protein homolog (S. cerevisiae) 559498 7 7 3 0 0 0 0 0 7 0 0.836 2.99e-06 0.00187
30 CDKN2C cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4) 408117 6 6 6 0 0 0 1 0 5 0 0.344 4.53e-06 0.00272
31 ANKRD30A ankyrin repeat domain 30A 2941613 16 15 16 2 6 1 3 4 2 0 0.0691 4.73e-06 0.00272
32 OR52M1 olfactory receptor, family 52, subfamily M, member 1 761684 8 8 8 0 4 0 2 2 0 0 0.121 4.84e-06 0.00272
33 LZTR1 leucine-zipper-like transcription regulator 1 1786974 15 15 15 0 5 1 1 6 2 0 0.0102 4.95e-06 0.00272
34 GABRA1 gamma-aminobutyric acid (GABA) A receptor, alpha 1 1118597 13 10 13 0 3 2 1 4 3 0 0.0149 7.37e-06 0.00393
35 SPANXD SPANX family, member D 237925 5 5 5 0 1 1 1 2 0 0 0.197 7.82e-06 0.00405
IDH1

Figure S1.  This figure depicts the distribution of mutations and mutation types across the IDH1 significant gene.

TP53

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

ATRX

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

CIC

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

EGFR

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

PIK3CA

Figure S6.  This figure depicts the distribution of mutations and mutation types across the PIK3CA significant gene.

NOTCH1

Figure S7.  This figure depicts the distribution of mutations and mutation types across the NOTCH1 significant gene.

PTEN

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

RB1

Figure S9.  This figure depicts the distribution of mutations and mutation types across the RB1 significant gene.

NF1

Figure S10.  This figure depicts the distribution of mutations and mutation types across the NF1 significant gene.

FUBP1

Figure S11.  This figure depicts the distribution of mutations and mutation types across the FUBP1 significant gene.

IDH2

Figure S12.  This figure depicts the distribution of mutations and mutation types across the IDH2 significant gene.

PIK3R1

Figure S13.  This figure depicts the distribution of mutations and mutation types across the PIK3R1 significant gene.

KEL

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

TCF12

Figure S15.  This figure depicts the distribution of mutations and mutation types across the TCF12 significant gene.

ZBTB20

Figure S16.  This figure depicts the distribution of mutations and mutation types across the ZBTB20 significant gene.

GABRA6

Figure S17.  This figure depicts the distribution of mutations and mutation types across the GABRA6 significant gene.

TPTE2

Figure S18.  This figure depicts the distribution of mutations and mutation types across the TPTE2 significant gene.

OR8K3

Figure S19.  This figure depicts the distribution of mutations and mutation types across the OR8K3 significant gene.

CDH18

Figure S20.  This figure depicts the distribution of mutations and mutation types across the CDH18 significant gene.

OR4P4

Figure S21.  This figure depicts the distribution of mutations and mutation types across the OR4P4 significant gene.

RPL5

Figure S22.  This figure depicts the distribution of mutations and mutation types across the RPL5 significant gene.

SEMG2

Figure S23.  This figure depicts the distribution of mutations and mutation types across the SEMG2 significant gene.

SPTA1

Figure S24.  This figure depicts the distribution of mutations and mutation types across the SPTA1 significant gene.

STK19

Figure S25.  This figure depicts the distribution of mutations and mutation types across the STK19 significant gene.

KIF2B

Figure S26.  This figure depicts the distribution of mutations and mutation types across the KIF2B significant gene.

UGT2A3

Figure S27.  This figure depicts the distribution of mutations and mutation types across the UGT2A3 significant gene.

STAG2

Figure S28.  This figure depicts the distribution of mutations and mutation types across the STAG2 significant gene.

EMG1

Figure S29.  This figure depicts the distribution of mutations and mutation types across the EMG1 significant gene.

CDKN2C

Figure S30.  This figure depicts the distribution of mutations and mutation types across the CDKN2C significant gene.

ANKRD30A

Figure S31.  This figure depicts the distribution of mutations and mutation types across the ANKRD30A significant gene.

OR52M1

Figure S32.  This figure depicts the distribution of mutations and mutation types across the OR52M1 significant gene.

LZTR1

Figure S33.  This figure depicts the distribution of mutations and mutation types across the LZTR1 significant gene.

GABRA1

Figure S34.  This figure depicts the distribution of mutations and mutation types across the GABRA1 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 408 356 393 283376 129977 0 0
2 EGFR epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian) 138 293 101 233228 1581 0 0
3 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 83 220 68 175120 15918 0 0
4 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 115 767 112 610532 3750 0 0
5 RB1 retinoblastoma 1 (including osteosarcoma) 30 267 18 212532 45 0 0
6 NF1 neurofibromin 1 (neurofibromatosis, von Recklinghausen disease, Watson disease) 68 285 19 226860 47 0 0
7 IDH1 isocitrate dehydrogenase 1 (NADP+), soluble 412 5 412 3980 614704 3.4e-14 2.2e-11
8 IDH2 isocitrate dehydrogenase 2 (NADP+), mitochondrial 20 6 20 4776 1660 4e-14 2.3e-11
9 ATRX alpha thalassemia/mental retardation syndrome X-linked (RAD54 homolog, S. cerevisiae) 216 4 5 3184 5 8.9e-14 4e-11
10 FUBP1 far upstream element (FUSE) binding protein 1 49 4 5 3184 2 8.9e-14 4e-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(6), AKT1(2), APAF1(3), ATM(12), BAX(1), BCL2(3), BIRC2(3), BIRC3(1), CAPN1(2), CASP10(2), 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(4), PIK3CA(83), PIK3CB(7), PIK3CD(3), PIK3CG(12), PIK3R1(56), PIK3R2(4), PIK3R3(2), PIK3R5(4), PPP3CA(1), PPP3CB(2), PPP3CC(1), PPP3R2(1), PRKACG(1), PRKAR1A(2), PRKAR1B(1), PRKAR2B(1), RELA(1), RIPK1(4), TNF(1), TNFRSF10C(1), TNFRSF10D(1), TNFRSF1A(1), TNFSF10(2), TP53(408), TRADD(1), TRAF2(2) 99368867 701 467 403 59 182 97 106 153 155 8 <1.00e-15 <1.00e-15 <2.37e-14
2 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), GPX1(1), GPX2(2), GPX4(2), GPX5(1), GSS(2), GSTA1(3), GSTA2(1), GSTA3(1), GSTA4(3), GSTM4(1), GSTM5(1), GSTT1(1), GSTZ1(3), IDH1(412), IDH2(20), PGD(1) 21465415 467 448 40 13 402 19 8 33 5 0 <1.00e-15 <1.00e-15 <2.37e-14
3 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(3), EGFR(138), IGF1R(10), POLR2A(9), PPP2CA(4), PRKCA(6), RB1(30), TEP1(12), TERF1(1), TERT(5), TNKS(2), TP53(408), XRCC5(4) 33523326 634 447 310 25 173 110 72 153 117 9 <1.00e-15 <1.00e-15 <2.37e-14
4 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 <2.37e-14
5 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(408) 24072269 607 438 306 14 150 74 94 116 164 9 <1.00e-15 <1.00e-15 <2.37e-14
6 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(412), IDH2(20), SUCLA2(1) 15772905 453 438 26 1 397 17 4 31 4 0 <1.00e-15 <1.00e-15 <2.37e-14
7 REDUCTIVE_CARBOXYLATE_CYCLE_CO2_FIXATION ACO1, ACO2, FH, IDH1, IDH2, MDH1, MDH2, SDHB, SUCLA2 9 ACO1(6), ACO2(4), FH(1), IDH1(412), IDH2(20), SUCLA2(1) 10558174 444 435 17 0 394 15 4 30 1 0 <1.00e-15 <1.00e-15 <2.37e-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(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(4), SMAD4(1), TBC1D8(4), TFDP1(1), TP53(408), WEE1(2) 130682876 650 408 400 72 180 87 83 149 140 11 <1.00e-15 <1.00e-15 <2.37e-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(3), BCL2L11(1), BIRC2(3), BIRC3(1), CASP1(8), CASP10(2), 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(3), 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(408), TRADD(1), TRAF1(1), TRAF2(2), TRAF3(1) 68081193 526 373 278 40 174 68 67 115 95 7 <1.00e-15 <1.00e-15 <2.37e-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(4), TFDP1(1), TGFB2(2), TGFB3(1), TP53(408) 35802895 503 365 253 13 147 54 70 106 118 8 <1.00e-15 <1.00e-15 <2.37e-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 1 5 1 6 7 10 0 0.0021 0.0082 1
2 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(8), IFNG(2), IL12B(4), IL18(3) 3542953 17 13 17 3 4 3 2 6 2 0 0.18 0.049 1
3 HSA00902_MONOTERPENOID_BIOSYNTHESIS Genes involved in monoterpenoid biosynthesis CYP2C19, CYP2C9 2 CYP2C19(6), CYP2C9(3) 2399460 9 9 9 2 4 3 0 1 1 0 0.35 0.049 1
4 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 4 6 2 5 5 11 0 0.043 0.057 1
5 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 0.11 1
6 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 0.12 1
7 RIBOFLAVIN_METABOLISM ACP1, ACP2, ACP5, ACPP, ACPT, ENPP1, ENPP3, FLAD1, RFK, TYR 10 ACP1(1), ACPP(4), ACPT(2), ENPP1(5), ENPP3(2), FLAD1(3), TYR(5) 11508628 22 19 22 1 8 2 4 6 2 0 0.0099 0.14 1
8 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 0.18 1
9 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 0.19 1
10 NUCLEOTIDE_SUGARS_METABOLISM GALE, GALT, TGDS, UGDH, UXS1 5 GALE(2), GALT(1), TGDS(2), UGDH(1), UXS1(4) 4580573 10 9 10 1 1 2 3 2 2 0 0.16 0.2 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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