Mutation Analysis (MutSig v2.0)
Brain Lower Grade Glioma (Primary solid tumor)
23 May 2013  |  analyses__2013_05_23
Maintainer Information
Citation Information
doi:10.7908/C1GH9G0S
Maintained by Dan DiCara (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Mutation Analysis (MutSig v2.0). Broad Institute of MIT and Harvard. doi:10.7908/C1GH9G0S
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: LGG-TP

  • Number of patients in set: 217

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:LGG-TP.final_analysis_set.maf

  • Significantly mutated genes (q ≤ 0.1): 30

  • Mutations seen in COSMIC: 425

  • Significantly mutated genes in COSMIC territory: 13

  • Genes with clustered mutations (≤ 3 aa apart): 159

  • Significantly mutated genesets: 100

  • Significantly mutated genesets: (excluding sig. mutated genes):1

Mutation Preprocessing

  • Read 217 MAFs of type "Broad"

  • Total number of mutations in input MAFs: 27275

  • After removing 13 mutations outside chr1-24: 27262

  • After removing 590 blacklisted mutations: 26672

  • After removing 573 noncoding mutations: 26099

Mutation Filtering

  • Number of mutations before filtering: 26099

  • After removing 361 mutations outside gene set: 25738

  • After removing 101 mutations outside category set: 25637

  • After removing 3 "impossible" mutations in

  • gene-patient-category bins of zero coverage: 25172

Results
Breakdown of Mutations by Type

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

type count
Frame_Shift_Del 584
Frame_Shift_Ins 291
In_Frame_Del 299
In_Frame_Ins 13
Missense_Mutation 16460
Nonsense_Mutation 1024
Nonstop_Mutation 13
Silent 6454
Splice_Site 453
Translation_Start_Site 46
Total 25637
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 5399 352259750 0.000015 15 5.1 2.1
*Cp(A/C/T)->T 3600 2893376300 1.2e-06 1.2 0.41 1.7
A->G 2256 3122700650 7.2e-07 0.72 0.24 2.3
transver 5250 6368336700 8.2e-07 0.82 0.27 5
indel+null 2587 6368336700 4.1e-07 0.41 0.13 NaN
double_null 89 6368336700 1.4e-08 0.014 0.0046 NaN
Total 19181 6368336700 3e-06 3 1 3.5
Target Coverage for Each Individual

The x axis represents the samples. The y axis represents the exons, one row per exon, and they are sorted by average coverage across samples. For exons with exactly the same average coverage, they are sorted next by the %GC of the exon. (The secondary sort is especially useful for the zero-coverage exons at the bottom).

Figure 1. 

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

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

Needs description.

Figure 3.  Needs description.

Figure 4.  Needs description.

CoMut Plot

Figure 5.  Get High-res Image The matrix in the center of the figure represents individual mutations in patient samples, color-coded by type of mutation, for the significantly mutated genes. The rate of synonymous and non-synonymous mutations is displayed at the top of the matrix. The barplot on the left of the matrix shows the number of mutations in each gene. The percentages represent the fraction of tumors with at least one mutation in the specified gene. The barplot to the right of the matrix displays the q-values for the most significantly mutated genes. The purple boxplots below the matrix (only displayed if required columns are present in the provided MAF) represent the distributions of allelic fractions observed in each sample. The plot at the bottom represents the base substitution distribution of individual samples, using the same categories that were used to calculate significance.

Significantly Mutated Genes

Column Descriptions:

  • N = number of sequenced bases in this gene across the individual set

  • n = number of (nonsilent) mutations in this gene across the individual set

  • npat = number of patients (individuals) with at least one nonsilent mutation

  • nsite = number of unique sites having a non-silent mutation

  • nsil = number of silent mutations in this gene across the individual set

  • n1 = number of nonsilent mutations of type: *CpG->T

  • n2 = number of nonsilent mutations of type: *Cp(A/C/T)->T

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

  • n4 = number of nonsilent mutations of type: transver

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

  • n6 = number of nonsilent mutations of type: double_null

  • p_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: 30. 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_cons p_joint p q
1 IDH1 isocitrate dehydrogenase 1 (NADP+), soluble 275139 165 165 2 0 155 0 0 10 0 0 1.55e-15 <1.00e-15 1 0 <1.00e-15 <4.52e-12
2 TP53 tumor protein p53 267086 148 113 76 2 58 15 21 31 20 3 <1.00e-15 1.55e-15 0 0 <1.00e-15 <4.52e-12
3 IDH2 isocitrate dehydrogenase 2 (NADP+), mitochondrial 252948 9 9 3 0 0 6 0 3 0 0 3.64e-12 0.0139 1 0 <1.00e-15 <4.52e-12
4 IL32 interleukin 32 113894 6 6 1 0 0 0 0 0 6 0 1.52e-09 1.000 0.98 0 <1.00e-15 <4.52e-12
5 PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (alpha) 512641 15 14 13 1 1 2 3 0 9 0 6.99e-15 0.263 0.85 0.021 5.55e-15 2.01e-11
6 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 712138 21 19 13 0 0 7 7 3 4 0 9.55e-15 0.00251 0.016 0.02 7.11e-15 2.14e-11
7 ATRX alpha thalassemia/mental retardation syndrome X-linked (RAD54 homolog, S. cerevisiae) 1632339 98 93 87 3 2 4 8 6 73 5 1.55e-15 0.00226 0.46 0.23 1.29e-14 3.33e-11
8 FUBP1 far upstream element (FUSE) binding protein 1 428208 22 22 21 2 0 0 1 2 19 0 <1.00e-15 0.560 0.9 0.56 <2.03e-14 <4.60e-11
9 NOTCH1 Notch homolog 1, translocation-associated (Drosophila) 1333631 26 19 23 3 4 3 1 6 9 3 2.05e-11 0.0592 0.027 0.000043 3.12e-14 6.13e-11
10 CIC capicua homolog (Drosophila) 909824 46 41 39 0 17 1 1 5 21 1 4.88e-15 3.55e-05 0.88 0.2 3.39e-14 6.13e-11
11 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 263317 12 12 12 0 1 1 1 6 3 0 7.33e-15 0.110 0.26 0.43 1.08e-13 1.77e-10
12 NF1 neurofibromin 1 (neurofibromatosis, von Recklinghausen disease, Watson disease) 1879261 20 16 19 1 1 2 1 3 7 6 1.31e-11 0.0534 0.76 0.12 4.53e-11 6.83e-08
13 ZNF844 zinc finger protein 844 272761 7 6 3 0 0 0 3 4 0 0 1.72e-07 0.155 0.99 0.0039 1.48e-08 2.06e-05
14 TCF12 transcription factor 12 (HTF4, helix-loop-helix transcription factors 4) 492075 10 9 9 0 0 0 0 0 10 0 1.99e-09 0.748 0.33 0.4 1.74e-08 2.25e-05
15 ZBTB20 zinc finger and BTB domain containing 20 441562 10 10 10 1 1 0 3 2 4 0 3.72e-09 0.297 0.43 0.33 2.67e-08 3.22e-05
16 TIMD4 T-cell immunoglobulin and mucin domain containing 4 254458 6 6 3 1 0 1 0 1 4 0 1.52e-07 0.814 0.58 0.012 3.75e-08 4.24e-05
17 ZNF57 zinc finger protein 57 363748 7 6 4 0 1 1 1 4 0 0 2.48e-05 0.159 1 0.00014 7.17e-08 7.55e-05
18 CREBZF CREB/ATF bZIP transcription factor 224089 4 4 1 0 0 0 0 0 4 0 0.000613 1.000 0.32 6e-06 7.51e-08 7.55e-05
19 ARID1A AT rich interactive domain 1A (SWI-like) 1260450 15 13 15 0 1 0 0 1 12 1 1.07e-08 0.0504 0.64 1 2.07e-07 0.000197
20 EGFR epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian) 854034 12 10 9 0 1 4 0 6 1 0 5.80e-07 0.0283 0.044 0.036 3.89e-07 0.000352
21 EMG1 EMG1 nucleolar protein homolog (S. cerevisiae) 148063 4 4 2 0 0 0 0 0 4 0 6.35e-06 0.837 0.74 0.13 1.24e-05 0.0107
22 PRDM9 PR domain containing 9 590602 7 6 7 1 2 1 1 3 0 0 5.46e-05 0.435 0.047 0.019 1.57e-05 0.0125
23 PRAMEF11 PRAME family member 11 268437 7 6 7 1 0 2 3 2 0 0 2.64e-06 0.322 0.85 0.41 1.59e-05 0.0125
24 NOX4 NADPH oxidase 4 390044 6 5 3 0 0 1 1 0 4 0 0.000228 0.449 0.54 0.0072 2.35e-05 0.0177
25 ANKRD30A ankyrin repeat domain 30A 807433 8 8 6 2 2 0 1 5 0 0 1.13e-05 0.442 0.63 0.34 5.19e-05 0.0375
26 MUC7 mucin 7, secreted 247807 8 5 7 0 1 2 5 0 0 0 1.24e-05 0.0185 0.49 0.35 5.81e-05 0.0404
27 ZNF845 zinc finger protein 845 606165 6 6 4 1 0 3 2 1 0 0 0.000115 0.324 0.99 0.056 8.41e-05 0.0560
28 PAX4 paired box 4 215510 5 5 5 1 2 1 0 2 0 0 1.54e-05 0.609 0.38 0.44 8.66e-05 0.0560
29 SPDYE5 speedy homolog E5 (Xenopus laevis) 186534 4 4 3 0 3 0 1 0 0 0 9.75e-05 0.380 0.72 0.12 0.000148 0.0898
30 C15orf2 chromosome 15 open reading frame 2 746118 9 8 9 1 3 2 1 2 1 0 1.64e-05 0.129 0.22 0.74 0.000149 0.0898
31 SCAF1 SR-related CTD-associated factor 1 428190 4 4 2 1 1 0 0 0 3 0 0.00472 0.935 0.18 0.0031 0.000175 0.102
32 FSTL5 follistatin-like 5 547028 8 6 8 1 0 2 1 2 3 0 5.61e-05 0.292 0.7 0.27 0.000185 0.105
33 C9orf79 chromosome 9 open reading frame 79 914534 9 8 9 0 2 3 2 1 1 0 2.09e-05 0.0419 0.71 0.79 0.000199 0.109
34 ZCCHC12 zinc finger, CCHC domain containing 12 263212 3 3 1 0 3 0 0 0 0 0 0.00375 0.410 0.74 0.0058 0.000255 0.136
35 SMARCA4 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4 980041 13 13 11 4 3 0 1 5 4 0 0.000496 0.740 0.37 0.052 0.000301 0.155
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.

IDH2

Figure S3.  This figure depicts the distribution of mutations and mutation types across the IDH2 significant gene.

IL32

Figure S4.  This figure depicts the distribution of mutations and mutation types across the IL32 significant gene.

PIK3R1

Figure S5.  This figure depicts the distribution of mutations and mutation types across the PIK3R1 significant gene.

PIK3CA

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

ATRX

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

FUBP1

Figure S8.  This figure depicts the distribution of mutations and mutation types across the FUBP1 significant gene.

NOTCH1

Figure S9.  This figure depicts the distribution of mutations and mutation types across the NOTCH1 significant gene.

CIC

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

PTEN

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

NF1

Figure S12.  This figure depicts the distribution of mutations and mutation types across the NF1 significant gene.

ZNF844

Figure S13.  This figure depicts the distribution of mutations and mutation types across the ZNF844 significant gene.

TCF12

Figure S14.  This figure depicts the distribution of mutations and mutation types across the TCF12 significant gene.

ZBTB20

Figure S15.  This figure depicts the distribution of mutations and mutation types across the ZBTB20 significant gene.

TIMD4

Figure S16.  This figure depicts the distribution of mutations and mutation types across the TIMD4 significant gene.

ZNF57

Figure S17.  This figure depicts the distribution of mutations and mutation types across the ZNF57 significant gene.

CREBZF

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

ARID1A

Figure S19.  This figure depicts the distribution of mutations and mutation types across the ARID1A significant gene.

EGFR

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

EMG1

Figure S21.  This figure depicts the distribution of mutations and mutation types across the EMG1 significant gene.

PRDM9

Figure S22.  This figure depicts the distribution of mutations and mutation types across the PRDM9 significant gene.

PRAMEF11

Figure S23.  This figure depicts the distribution of mutations and mutation types across the PRAMEF11 significant gene.

NOX4

Figure S24.  This figure depicts the distribution of mutations and mutation types across the NOX4 significant gene.

ANKRD30A

Figure S25.  This figure depicts the distribution of mutations and mutation types across the ANKRD30A significant gene.

MUC7

Figure S26.  This figure depicts the distribution of mutations and mutation types across the MUC7 significant gene.

ZNF845

Figure S27.  This figure depicts the distribution of mutations and mutation types across the ZNF845 significant gene.

PAX4

Figure S28.  This figure depicts the distribution of mutations and mutation types across the PAX4 significant gene.

SPDYE5

Figure S29.  This figure depicts the distribution of mutations and mutation types across the SPDYE5 significant gene.

C15orf2

Figure S30.  This figure depicts the distribution of mutations and mutation types across the C15orf2 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: 13. 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 165 5 165 1085 246180 4.8e-14 1.3e-10
2 IDH2 isocitrate dehydrogenase 2 (NADP+), mitochondrial 9 6 9 1302 747 5.8e-14 1.3e-10
3 PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (alpha) 15 33 7 7161 14 3.1e-13 4.7e-10
4 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 21 220 19 47740 2990 1.8e-12 2.1e-09
5 TP53 tumor protein p53 148 356 145 77252 51945 2.7e-12 2.5e-09
6 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 12 767 11 166439 549 1.2e-11 9.4e-09
7 PTPN11 protein tyrosine phosphatase, non-receptor type 11 (Noonan syndrome 1) 6 32 5 6944 178 3.3e-11 2.1e-08
8 EGFR epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian) 12 293 8 63581 71 4e-11 2.3e-08
9 SMARCA4 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4 13 30 4 6510 1 6.1e-09 3e-06
10 NF1 neurofibromin 1 (neurofibromatosis, von Recklinghausen disease, Watson disease) 20 285 6 61845 8 4.9e-08 0.000022

Note:

n - number of (nonsilent) mutations in this gene across the individual set.

cos = number of unique mutated sites in this gene in COSMIC

n_cos = overlap between n and cos.

N_cos = number of individuals times cos.

cos_ev = total evidence: number of reports in COSMIC for mutations seen in this gene.

p = p-value for seeing the observed amount of overlap in this gene)

q = q-value, False Discovery Rate (Benjamini-Hochberg procedure)

Clustered Mutations

Table 5.  Get Full Table Genes with Clustered Mutations

num gene desc n mindist nmuts0 nmuts3 nmuts12 npairs0 npairs3 npairs12
3837 IDH1 isocitrate dehydrogenase 1 (NADP+), soluble 165 0 13530 13530 13530 13530 13530 13530
8611 TP53 tumor protein p53 148 0 684 1017 1745 684 1017 1745
3838 IDH2 isocitrate dehydrogenase 2 (NADP+), mitochondrial 9 0 36 36 36 36 36 36
1763 CIC capicua homolog (Drosophila) 46 0 19 29 55 19 29 55
723 ATRX alpha thalassemia/mental retardation syndrome X-linked (RAD54 homolog, S. cerevisiae) 98 0 15 21 30 15 21 30
6274 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 21 0 9 11 17 9 11 17
9636 ZNF844 zinc finger protein 844 7 0 7 7 15 7 7 15
9527 ZNF57 zinc finger protein 57 7 0 6 6 14 6 6 14
2590 EGFR epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian) 12 0 5 5 5 5 5 5
424 ANKRD30A ankyrin repeat domain 30A 8 0 3 3 3 3 3 3

Note:

n - number of mutations in this gene in the individual set.

mindist - distance (in aa) between closest pair of mutations in this gene

npairs3 - how many pairs of mutations are within 3 aa of each other.

npairs12 - how many pairs of mutations are within 12 aa of each other.

Geneset Analyses

Table 6.  Get Full Table A Ranked List of Significantly Mutated Genesets. (Source: MSigDB GSEA Cannonical Pathway Set).Number of significant genesets found: 100. 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 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(3), ACO1(2), ACO2(2), ACSS1(1), ACSS2(3), FH(1), IDH1(165), IDH2(9) 4296350 186 177 17 0 160 8 0 16 2 0 <1.00e-15 <1.00e-15 <8.80e-14
2 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(2), ACO2(2), FH(1), IDH1(165), IDH2(9), IDH3B(1), PC(1), PCK1(3), SUCLG2(1) 6652756 185 175 16 2 160 10 0 15 0 0 <1.00e-15 <1.00e-15 <8.80e-14
3 ARFPATHWAY Cyclin-dependent kinase inhibitor 2A is a tumor suppressor that induces G1 arrest and can activate the p53 pathway, leading to G2/M arrest. ABL1, CDKN2A, E2F1, MDM2, MYC, PIK3CA, PIK3R1, POLR1A, POLR1B, POLR1C, POLR1D, RAC1, RB1, TBX2, TP53, TWIST1 16 ABL1(4), CDKN2A(2), E2F1(1), MDM2(2), PIK3CA(21), PIK3R1(15), POLR1A(4), POLR1B(2), RAC1(1), RB1(4), TBX2(1), TP53(148) 6553032 205 141 123 9 64 26 34 39 39 3 <1.00e-15 <1.00e-15 <8.80e-14
4 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(4), BAX(1), CCND1(1), CDK2(1), CDK4(1), E2F1(1), MDM2(2), RB1(4), TIMP3(2), TP53(148) 5848889 166 117 94 6 61 17 26 35 24 3 1.32e-14 <1.00e-15 <8.80e-14
5 RBPATHWAY The ATM protein kinase recognizes DNA damage and blocks cell cycle progression by phosphorylating chk1 and p53, which normally inhibits Rb to allow G1/S transitions. ATM, CDC2, CDC25A, CDC25B, CDC25C, CDK2, CDK4, CHEK1, MYT1, RB1, TP53, WEE1, YWHAH 12 ATM(4), CDC25A(1), CDK2(1), CDK4(1), CHEK1(3), MYT1(3), RB1(4), TP53(148), WEE1(1), YWHAH(1) 5683263 167 117 95 9 61 17 24 33 29 3 2.39e-11 <1.00e-15 <8.80e-14
6 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(4), BRCA1(1), CHEK1(3), CHEK2(3), MAPK8(1), MDM2(2), MRE11A(2), NFKB1(1), RAD50(2), RBBP8(2), RELA(1), TP53(148) 9630116 174 115 102 13 64 22 24 38 23 3 1.64e-10 <1.00e-15 <8.80e-14
7 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 ARF1(1), CCND1(1), CDK2(1), CDK4(1), CDKN1B(1), CDKN2A(2), CFL1(1), E2F1(1), MDM2(2), PRB1(2), TP53(148) 2712441 161 114 89 7 61 17 24 34 22 3 3.65e-14 <1.00e-15 <8.80e-14
8 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 MAX(4), SP3(2), TP53(148), WT1(1) 2279162 155 116 82 2 61 16 21 34 20 3 <1.00e-15 1.22e-15 9.12e-14
9 REDUCTIVE_CARBOXYLATE_CYCLE_CO2_FIXATION ACO1, ACO2, FH, IDH1, IDH2, MDH1, MDH2, SDHB, SUCLA2 9 ACO1(2), ACO2(2), FH(1), IDH1(165), IDH2(9) 2876483 179 175 10 0 158 7 0 14 0 0 1.22e-15 1.33e-15 9.12e-14
10 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(3), AKT1(1), ATM(4), BAX(1), CPB2(1), CSNK1A1(2), CSNK1D(1), IGFBP3(1), MAPK8(1), MDM2(2), TP53(148) 6705131 165 115 93 9 62 17 24 37 22 3 8.04e-13 1.55e-15 9.40e-14

Table 7.  Get Full Table A Ranked List of Significantly Mutated Genesets (Excluding Significantly Mutated Genes). Number of significant genesets found: 1. 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 HSA00902_MONOTERPENOID_BIOSYNTHESIS Genes involved in monoterpenoid biosynthesis CYP2C19, CYP2C9 2 CYP2C19(5), CYP2C9(1) 653807 6 6 6 0 3 1 0 1 1 0 0.21 0.0001 0.062
2 FLUMAZENILPATHWAY Flumazenil is a benzodiazepine receptor antagonist that may induce protective preconditioning in ischemic cardiomyocytes. GABRA1, GABRA2, GABRA3, GABRA4, GABRA5, GABRA6, GPX1, PRKCE, SOD1 9 GABRA1(7), GABRA3(1), GABRA4(5), GABRA5(1), GABRA6(3) 2546874 17 11 17 4 4 5 1 5 2 0 0.24 0.0024 0.72
3 HSA00592_ALPHA_LINOLENIC_ACID_METABOLISM Genes involved in alpha-Linolenic acid metabolism ACOX1, ACOX3, FADS2, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6 15 ACOX1(2), ACOX3(3), FADS2(2), PLA2G12B(1), PLA2G2D(1), PLA2G3(3), PLA2G4A(4), PLA2G5(1), PLA2G6(2) 3275210 19 10 19 2 4 4 3 6 2 0 0.059 0.0046 0.94
4 SLRPPATHWAY Small leucine-rich proteoglycans (SLRPs) interact with and reorganize collagen fibers in the extracellular matrix. BGN, DCN, DSPG3, FMOD, KERA, LUM 5 BGN(2), DCN(1), FMOD(1), KERA(2), LUM(2) 1171353 8 7 8 3 1 1 2 4 0 0 0.7 0.023 1
5 P27PATHWAY p27 blocks the G1/S transition by inhibiting the checkpoint kinase cdk2/cyclin E and is inhibited by cdk2-mediated ubiquitination. CCNE1, CDK2, CDKN1B, CKS1B, CUL1, E2F1, NEDD8, RB1, RBX1, SKP1A, SKP2, TFDP1, UBE2M 12 CDK2(1), CDKN1B(1), CUL1(1), E2F1(1), RB1(4), SKP2(2), UBE2M(1) 2767786 11 8 11 1 1 1 4 1 4 0 0.17 0.026 1
6 CBLPATHWAY Activated EGF receptors undergo endocytosis into clathrin-coated vesicles, where they are recycled to the membrane or ubiquitinated by Cbl. CBL, CSF1R, EGF, EGFR, GRB2, MET, PDGFRA, PRKCA, PRKCB1, SH3GLB1, SH3GLB2, SH3KBP1, SRC 11 CSF1R(3), EGF(3), MET(6), PDGFRA(8), PRKCA(3), SH3GLB1(3), SH3KBP1(3) 5420381 29 13 28 8 9 5 4 6 4 1 0.21 0.026 1
7 HSA00565_ETHER_LIPID_METABOLISM Genes involved in ether lipid metabolism AGPAT1, AGPAT2, AGPAT3, AGPAT4, AGPAT6, AGPS, CHPT1, ENPP2, ENPP6, LYCAT, PAFAH1B1, PAFAH1B2, PAFAH1B3, PAFAH2, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, PLD1, PLD2, PPAP2A, PPAP2B, PPAP2C 30 AGPAT3(1), AGPS(2), ENPP2(2), ENPP6(1), PAFAH1B1(4), PAFAH1B3(1), PAFAH2(2), PLA2G12B(1), PLA2G2D(1), PLA2G3(3), PLA2G4A(4), PLA2G5(1), PLA2G6(2), PLD1(4), PPAP2A(2), PPAP2C(1) 7485397 32 16 32 7 5 6 6 12 3 0 0.16 0.027 1
8 SKP2E2FPATHWAY E2F-1, a transcription factor that promotes the G1/S transition, is repressed by Rb and activated by cdk2/cyclin E. CCNA1, CCNE1, CDC34, CDK2, CUL1, E2F1, RB1, SKP1A, SKP2, TFDP1 9 CCNA1(1), CDC34(1), CDK2(1), CUL1(1), E2F1(1), RB1(4), SKP2(2) 2759061 11 8 11 1 1 1 4 1 4 0 0.19 0.029 1
9 PLCPATHWAY Phospholipase C hydrolyzes the membrane lipid PIP2 to DAG, which activates protein kinase C, and IP3, which causes calcium influx. AKT1, PIK3CA, PIK3R1, PLCB1, PLCG1, PRKCA, PRKCB1, VAV1 5 AKT1(1), PLCB1(2), PLCG1(6), PRKCA(3), VAV1(4) 2922753 16 11 15 3 4 3 2 5 1 1 0.24 0.042 1
10 HSA00232_CAFFEINE_METABOLISM Genes involved in caffeine metabolism CYP1A2, CYP2A13, CYP2A6, CYP2A7, NAT1, NAT2, XDH 7 CYP1A2(2), NAT1(1), NAT2(2), XDH(7) 2572389 12 7 12 0 4 1 0 5 2 0 0.036 0.064 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

This is an experimental feature. The full results of the analysis summarized in this report can be downloaded from the TCGA Data Coordination Center.

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