Mutation Analysis (MutSig v2.0)
Bladder Urothelial Carcinoma (Primary solid tumor)
17 October 2014  |  analyses__2014_10_17
Maintainer Information
Citation Information
doi:10.7908/C1NV9H3J
Maintained by David Heiman (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2014): Mutation Analysis (MutSig v2.0). Broad Institute of MIT and Harvard. doi:10.7908/C1NV9H3J
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: BLCA-TP

  • Number of patients in set: 130

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:BLCA-TP.final_analysis_set.maf

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

  • Significantly mutated genes (q ≤ 0.1): 33

  • Mutations seen in COSMIC: 216

  • Significantly mutated genes in COSMIC territory: 10

  • Significantly mutated genesets: 21

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

Mutation Preprocessing

  • Read 130 MAFs of type "Broad"

  • Total number of mutations in input MAFs: 39312

  • After removing 613 blacklisted mutations: 38699

Mutation Filtering

  • Number of mutations before filtering: 38699

  • After removing 1 "impossible" mutations in

  • gene-patient-category bins of zero coverage: 38698

Results
Breakdown of Mutations by Type

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

type count
Frame_Shift_Del 512
Frame_Shift_Ins 219
In_Frame_Del 151
In_Frame_Ins 20
Missense_Mutation 24876
Nonsense_Mutation 2214
Nonstop_Mutation 47
Silent 10012
Splice_Site 590
Translation_Start_Site 58
Total 38699
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
Tp*C->(T/G) 14949 505003340 3e-05 30 3.9 3
Tp*C->A 1104 505003340 2.2e-06 2.2 0.29 4
(A/C/G)p*C->mut 5935 1437554646 4.1e-06 4.1 0.55 3.2
A->mut 2944 1865090498 1.6e-06 1.6 0.21 3.9
indel+null 3754 3807648484 9.9e-07 0.99 0.13 NaN
double_null 0 3807648484 0 0 0 NaN
Total 28686 3807648484 7.5e-06 7.5 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: BLCA-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: Tp*C->(T/G)

  • n2 = number of nonsilent mutations of type: Tp*C->A

  • n3 = number of nonsilent mutations of type: (A/C/G)p*C->mut

  • n4 = number of nonsilent mutations of type: A->mut

  • 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: 33. 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 TP53 tumor protein p53 158975 75 64 50 1 19 0 34 4 18 0 1.22e-15 1.7e-07 0 0 0 <1.00e-15 <9.05e-12
2 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 423746 26 26 11 1 22 2 0 2 0 0 7.11e-15 0.04 0 0.00012 0 <1.00e-15 <9.05e-12
3 KDM6A lysine (K)-specific demethylase 6A 498061 32 31 26 2 2 0 2 0 28 0 2.00e-15 0.24 0.22 0.098 0.2 1.45e-14 8.77e-11
4 ARID1A AT rich interactive domain 1A (SWI-like) 760474 38 32 36 2 10 1 0 1 26 0 <1.00e-15 0.035 0.81 0.72 1 <3.55e-14 <1.61e-10
5 CDKN1A cyclin-dependent kinase inhibitor 1A (p21, Cip1) 63890 18 18 17 0 1 0 2 0 15 0 7.77e-15 0.17 0.11 0.46 0.18 5.05e-14 1.83e-10
6 FGFR3 fibroblast growth factor receptor 3 (achondroplasia, thanatophoric dwarfism) 249631 21 16 11 2 12 0 7 1 1 0 1.89e-09 0.024 1e-06 0.12 5e-06 3.14e-13 9.47e-10
7 RB1 retinoblastoma 1 (including osteosarcoma) 328495 19 17 17 0 2 1 0 1 15 0 2.71e-13 0.04 0.36 0.72 0.51 4.23e-12 1.09e-08
8 FBXW7 F-box and WD repeat domain containing 7 317856 16 13 12 0 4 0 5 1 6 0 7.20e-09 0.046 0.000016 0.023 3e-05 6.43e-12 1.45e-08
9 NFE2L2 nuclear factor (erythroid-derived 2)-like 2 231964 12 11 9 0 7 0 2 3 0 0 2.84e-08 0.09 0.0023 0.0052 0.0002 1.49e-10 3.00e-07
10 ERCC2 excision repair cross-complementing rodent repair deficiency, complementation group 2 (xeroderma pigmentosum D) 280493 16 16 13 2 4 1 4 7 0 0 9.57e-10 0.14 0.42 0.019 0.073 1.70e-09 3.08e-06
11 ELF3 E74-like factor 3 (ets domain transcription factor, epithelial-specific ) 147808 15 11 14 0 3 0 2 1 9 0 2.16e-10 0.13 0.5 0.37 0.52 2.67e-09 4.39e-06
12 RXRA retinoid X receptor, alpha 181152 12 12 6 2 6 2 3 1 0 0 5.97e-08 0.12 0.0059 0.029 0.0027 3.78e-09 5.70e-06
13 CDKN2A cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) 96310 8 7 8 0 2 0 2 0 4 0 2.78e-06 0.16 0.13 0.0002 0.00067 3.93e-08 5.47e-05
14 FOXQ1 forkhead box Q1 48787 7 7 4 1 3 0 0 0 4 0 2.10e-08 0.4 0.23 0.046 0.11 4.80e-08 6.20e-05
15 ERBB3 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) 545990 14 14 10 1 5 2 5 2 0 0 3.19e-06 0.096 0.0006 0.64 0.0018 1.15e-07 0.000138
16 TPTE transmembrane phosphatase with tensin homology 224856 8 8 8 0 1 0 2 4 1 0 4.09e-05 0.16 0.14 0.00047 0.0026 1.84e-06 0.00208
17 MLL2 myeloid/lymphoid or mixed-lineage leukemia 2 1849473 40 36 40 5 10 0 3 2 25 0 7.54e-07 0.16 0.58 0.46 0.79 9.15e-06 0.00948
18 STAG2 stromal antigen 2 504437 14 14 13 3 2 0 0 0 12 0 2.91e-06 0.9 0.13 0.28 0.21 9.42e-06 0.00948
19 HRAS v-Ha-ras Harvey rat sarcoma viral oncogene homolog 83575 6 6 5 0 2 0 4 0 0 0 2.95e-05 0.11 0.049 0.011 0.023 1.04e-05 0.00994
20 KLF5 Kruppel-like factor 5 (intestinal) 146260 11 10 10 2 5 1 2 0 3 0 3.85e-06 0.58 0.75 0.056 0.21 1.20e-05 0.0109
21 EP300 E1A binding protein p300 955361 26 21 26 3 7 2 4 4 9 0 1.06e-05 0.24 0.065 0.43 0.1 1.62e-05 0.0140
22 TXNIP thioredoxin interacting protein 157040 12 9 12 2 3 1 2 1 5 0 1.31e-05 0.66 0.23 0.034 0.11 2.10e-05 0.0173
23 RHOB ras homolog gene family, member B 77227 7 7 6 1 3 0 4 0 0 0 3.76e-06 0.21 0.47 0.29 0.53 2.83e-05 0.0218
24 BTG2 BTG family, member 2 46207 6 6 6 0 3 0 2 0 1 0 3.46e-06 0.13 0.32 0.49 0.59 2.89e-05 0.0218
25 FOXA1 forkhead box A1 135106 7 7 7 1 2 0 0 0 5 0 5.08e-06 0.81 0.45 0.25 0.44 3.15e-05 0.0228
26 CREBBP CREB binding protein (Rubinstein-Taybi syndrome) 906790 18 17 17 3 5 0 6 1 6 0 0.00137 0.25 0.0012 0.75 0.0027 5.01e-05 0.0349
27 ASXL2 additional sex combs like 2 (Drosophila) 550886 11 9 11 0 6 0 1 0 4 0 0.0157 0.074 0.00072 0.0093 0.00028 5.81e-05 0.0389
28 PHLDA3 pleckstrin homology-like domain, family A, member 3 43621 4 4 3 1 2 0 1 0 1 0 0.000354 0.42 0.014 0.18 0.014 6.58e-05 0.0426
29 CX3CL1 chemokine (C-X3-C motif) ligand 1 156672 5 5 5 1 2 0 2 0 1 0 0.00259 0.52 0.02 0.029 0.0044 0.000141 0.0868
30 GPC5 glypican 5 217030 8 8 8 1 3 1 1 1 2 0 2.48e-05 0.37 0.31 0.58 0.47 0.000144 0.0868
31 MIPOL1 mirror-image polydactyly 1 169688 7 7 6 1 5 0 0 0 2 0 0.000250 0.63 0.035 0.23 0.048 0.000149 0.0868
32 SPTAN1 spectrin, alpha, non-erythrocytic 1 (alpha-fodrin) 966972 34 15 34 9 20 1 4 0 9 0 0.0565 0.65 0.0001 0.26 0.00022 0.000154 0.0872
33 ZFP36L1 zinc finger protein 36, C3H type-like 1 132732 6 6 6 0 0 0 1 2 3 0 4.77e-05 0.36 0.18 0.81 0.3 0.000173 0.0950
34 PAIP1 poly(A) binding protein interacting protein 1 157469 7 7 7 0 4 0 0 2 1 0 0.000101 0.27 0.56 0.059 0.22 0.000262 0.139
35 TSC1 tuberous sclerosis 1 463238 11 11 11 0 2 0 1 0 8 0 0.000163 0.086 0.17 0.11 0.16 0.000304 0.157
TP53

Figure S1.  This figure depicts the distribution of mutations and mutation types across the TP53 significant gene.

PIK3CA

Figure S2.  This figure depicts the distribution of mutations and mutation types across the PIK3CA significant gene.

KDM6A

Figure S3.  This figure depicts the distribution of mutations and mutation types across the KDM6A significant gene.

ARID1A

Figure S4.  This figure depicts the distribution of mutations and mutation types across the ARID1A significant gene.

CDKN1A

Figure S5.  This figure depicts the distribution of mutations and mutation types across the CDKN1A significant gene.

FGFR3

Figure S6.  This figure depicts the distribution of mutations and mutation types across the FGFR3 significant gene.

RB1

Figure S7.  This figure depicts the distribution of mutations and mutation types across the RB1 significant gene.

FBXW7

Figure S8.  This figure depicts the distribution of mutations and mutation types across the FBXW7 significant gene.

NFE2L2

Figure S9.  This figure depicts the distribution of mutations and mutation types across the NFE2L2 significant gene.

ERCC2

Figure S10.  This figure depicts the distribution of mutations and mutation types across the ERCC2 significant gene.

ELF3

Figure S11.  This figure depicts the distribution of mutations and mutation types across the ELF3 significant gene.

RXRA

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

CDKN2A

Figure S13.  This figure depicts the distribution of mutations and mutation types across the CDKN2A significant gene.

FOXQ1

Figure S14.  This figure depicts the distribution of mutations and mutation types across the FOXQ1 significant gene.

ERBB3

Figure S15.  This figure depicts the distribution of mutations and mutation types across the ERBB3 significant gene.

TPTE

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

MLL2

Figure S17.  This figure depicts the distribution of mutations and mutation types across the MLL2 significant gene.

STAG2

Figure S18.  This figure depicts the distribution of mutations and mutation types across the STAG2 significant gene.

HRAS

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

KLF5

Figure S20.  This figure depicts the distribution of mutations and mutation types across the KLF5 significant gene.

EP300

Figure S21.  This figure depicts the distribution of mutations and mutation types across the EP300 significant gene.

TXNIP

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

RHOB

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

BTG2

Figure S24.  This figure depicts the distribution of mutations and mutation types across the BTG2 significant gene.

FOXA1

Figure S25.  This figure depicts the distribution of mutations and mutation types across the FOXA1 significant gene.

CREBBP

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

ASXL2

Figure S27.  This figure depicts the distribution of mutations and mutation types across the ASXL2 significant gene.

PHLDA3

Figure S28.  This figure depicts the distribution of mutations and mutation types across the PHLDA3 significant gene.

MIPOL1

Figure S29.  This figure depicts the distribution of mutations and mutation types across the MIPOL1 significant gene.

SPTAN1

Figure S30.  This figure depicts the distribution of mutations and mutation types across the SPTAN1 significant gene.

ZFP36L1

Figure S31.  This figure depicts the distribution of mutations and mutation types across the ZFP36L1 significant gene.

COSMIC analyses

In this analysis, COSMIC is used as a filter to increase power by restricting the territory of each gene. Cosmic version: v48.

Table 4.  Get Full Table Significantly mutated genes (COSMIC territory only). To access the database please go to: COSMIC. Number of significant genes found: 10. Number of genes displayed: 10

rank gene description n cos n_cos N_cos cos_ev p q
1 FGFR3 fibroblast growth factor receptor 3 (achondroplasia, thanatophoric dwarfism) 21 62 15 8060 10223 0 0
2 TP53 tumor protein p53 75 356 72 46280 19158 0 0
3 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 26 220 21 28600 10307 0 0
4 FBXW7 F-box and WD repeat domain containing 7 16 91 8 11830 176 0 0
5 RB1 retinoblastoma 1 (including osteosarcoma) 19 267 10 34710 38 1.9e-14 1.7e-11
6 ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian) 11 42 5 5460 16 9.5e-10 7.1e-07
7 CDKN2A cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) 8 332 8 43160 214 2.3e-09 1.5e-06
8 HRAS v-Ha-ras Harvey rat sarcoma viral oncogene homolog 6 19 4 2470 1325 4.9e-09 2.8e-06
9 ATM ataxia telangiectasia mutated 19 245 7 31850 11 7.4e-09 3.7e-06
10 ERBB3 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) 14 6 3 780 3 3.4e-08 0.000015

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: 21. 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 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(18), DAXX(1), HRAS(6), PAX3(4), PML(3), RARA(3), RB1(19), SIRT1(1), SP100(6), TNFRSF1B(3), TP53(75) 3649856 139 81 109 8 41 1 51 7 39 0 2.1e-08 <1.00e-15 <3.08e-13
2 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 ARF3(1), CCND1(1), CDK2(1), CDK4(2), CDKN1A(18), CDKN1B(5), CDKN2A(8), E2F1(1), E2F2(1), PRB1(1), TP53(75) 1619397 114 76 88 5 28 0 39 5 42 0 2.5e-07 <1.00e-15 <3.08e-13
3 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 HDAC1(1), MYC(1), SP1(3), SP3(2), TP53(75), WT1(2) 1363520 84 68 59 4 23 1 34 5 21 0 8.7e-06 3.77e-15 7.75e-13
4 TIDPATHWAY On ligand binding, interferon gamma receptors stimulate JAK2 kinase to phosphorylate STAT transcription factors, which promote expression of interferon responsive genes. DNAJA3, HSPA1A, IFNG, IFNGR1, IFNGR2, IKBKB, JAK2, LIN7A, NFKB1, NFKBIA, RB1, RELA, TIP-1, TNF, TNFRSF1A, TNFRSF1B, TP53, USH1C, WT1 18 DNAJA3(1), HSPA1A(2), IFNG(1), IFNGR2(2), IKBKB(4), JAK2(2), NFKB1(1), NFKBIA(2), RB1(19), RELA(2), TNFRSF1B(3), TP53(75), USH1C(1), WT1(2) 3492287 117 73 90 6 33 2 40 5 37 0 1.3e-07 5.11e-15 7.86e-13
5 RNAPATHWAY dsRNA-activated protein kinase phosphorylates elF2a, which generally inhibits translation, and activates NF-kB to provoke inflammation. CHUK, DNAJC3, EIF2S1, EIF2S2, MAP3K14, NFKB1, NFKBIA, PRKR, RELA, TP53 9 CHUK(6), DNAJC3(2), MAP3K14(2), NFKB1(1), NFKBIA(2), RELA(2), TP53(75) 1894134 90 67 65 4 27 0 36 4 23 0 5e-06 8.44e-15 1.04e-12
6 FBW7PATHWAY Cyclin E interacts with cell cycle checkpoint kinase cdk2 to allow transcription of genes required for S phase, including transcription of additional cyclin E. CCNE1, CDC34, CDK2, CUL1, E2F1, FBXW7, RB1, SKP1A, TFDP1 8 CDK2(1), CUL1(8), E2F1(1), FBXW7(16), RB1(19) 1585537 45 36 38 1 14 1 6 2 22 0 0.0004 1.35e-13 1.38e-11
7 P53PATHWAY p53 induces cell cycle arrest or apoptosis under conditions of DNA damage. APAF1, ATM, BAX, BCL2, CCND1, CCNE1, CDK2, CDK4, CDKN1A, E2F1, GADD45A, MDM2, PCNA, RB1, TIMP3, TP53 16 APAF1(1), ATM(19), BAX(1), CCND1(1), CDK2(1), CDK4(2), CDKN1A(18), E2F1(1), GADD45A(1), PCNA(1), RB1(19), TP53(75) 3493410 140 87 112 12 36 2 41 8 53 0 0.00029 1.65e-12 1.45e-10
8 CELLCYCLEPATHWAY Cyclins interact with cyclin-dependent kinases to form active kinase complexes that regulate progression through the cell cycle. CCNA1, CCNB1, CCND1, CCND2, CCND3, CCNE1, CCNH, CDC2, CDC25A, CDK2, CDK4, CDK6, CDK7, CDKN1A, CDKN1B, CDKN2A, CDKN2B, CDKN2C, CDKN2D, E2F1, RB1, RBL1, TFDP1 22 CCNA1(1), CCNB1(1), CCND1(1), CCND3(5), CCNH(3), CDC25A(1), CDK2(1), CDK4(2), CDK6(1), CDK7(3), CDKN1A(18), CDKN1B(5), CDKN2A(8), CDKN2B(2), CDKN2D(1), E2F1(1), RB1(19), RBL1(1) 3072916 74 51 71 5 19 2 10 3 40 0 0.0021 5.47e-12 4.21e-10
9 ARFPATHWAY Cyclin-dependent kinase inhibitor 2A is a tumor suppressor that induces G1 arrest and can activate the p53 pathway, leading to G2/M arrest. ABL1, CDKN2A, E2F1, MDM2, MYC, PIK3CA, PIK3R1, POLR1A, POLR1B, POLR1C, POLR1D, RAC1, RB1, TBX2, TP53, TWIST1 16 ABL1(4), CDKN2A(8), E2F1(1), MYC(1), PIK3CA(26), PIK3R1(2), POLR1A(5), POLR1B(1), POLR1C(1), POLR1D(2), RAC1(1), RB1(19), TBX2(3), TP53(75) 3902579 149 79 107 12 57 4 40 9 39 0 8e-07 8.37e-12 5.73e-10
10 RACCYCDPATHWAY Ras, Rac, and Rho coordinate to induce cyclin D1 expression and activate cdk2 to promote the G1/S transition. AKT1, ARHA, CCND1, CCNE1, CDK2, CDK4, CDK6, CDKN1A, CDKN1B, E2F1, HRAS, MAPK1, MAPK3, NFKB1, NFKBIA, PAK1, PIK3CA, PIK3R1, RAC1, RAF1, RB1, RELA, TFDP1 22 CCND1(1), CDK2(1), CDK4(2), CDK6(1), CDKN1A(18), CDKN1B(5), E2F1(1), HRAS(6), MAPK3(3), NFKB1(1), NFKBIA(2), PIK3CA(26), PIK3R1(2), RAC1(1), RAF1(1), RB1(19), RELA(2) 3908128 92 64 73 8 40 3 9 5 35 0 0.001 1.05e-09 6.45e-08

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 HSA00730_THIAMINE_METABOLISM Genes involved in thiamine metabolism LHPP, MTMR1, MTMR2, MTMR6, NFS1, PHPT1, THTPA, TPK1 8 LHPP(2), MTMR1(2), MTMR2(3), MTMR6(4), NFS1(3), THTPA(1), TPK1(2) 1240248 17 14 17 0 12 0 1 1 3 0 0.019 0.068 1
2 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 CCR3(3), HLA-DRA(1), HLA-DRB1(1) 588486 5 5 5 1 0 0 3 1 1 0 0.62 0.18 1
3 PEPIPATHWAY Proepithelin (PEPI) induces epithelial cells to secrete IL-8, which promotes elastase secretion by neutrophils. ELA1, ELA2, ELA2A, ELA2B, ELA3B, GRN, IL8, SLPI 3 GRN(3), IL8(1) 331437 4 4 4 0 2 0 0 0 2 0 0.4 0.19 1
4 FBW7PATHWAY Cyclin E interacts with cell cycle checkpoint kinase cdk2 to allow transcription of genes required for S phase, including transcription of additional cyclin E. CCNE1, CDC34, CDK2, CUL1, E2F1, FBXW7, RB1, SKP1A, TFDP1 6 CDK2(1), CUL1(8), E2F1(1) 939186 10 10 9 1 8 0 1 0 1 0 0.19 0.19 1
5 HSA00940_PHENYLPROPANOID_BIOSYNTHESIS Genes involved in phenylpropanoid biosynthesis EPX, GBA, GBA3, LPO, MPO, PRDX6, TPO 7 EPX(2), GBA(2), GBA3(2), LPO(4), MPO(2), PRDX6(4), TPO(9) 1614846 25 21 24 4 10 0 9 3 3 0 0.1 0.22 1
6 ST_INTERFERON_GAMMA_PATHWAY The interferon gamma pathway resembles the JAK-STAT pathway and activates STAT transcription factors. CISH, IFNG, IFNGR1, JAK1, JAK2, PLA2G2A, PTPRU, REG1A, STAT1, STATIP1 9 CISH(1), IFNG(1), JAK1(3), JAK2(2), PLA2G2A(1), PTPRU(4), REG1A(3), STAT1(4) 2213957 19 18 19 1 11 0 4 2 2 0 0.027 0.23 1
7 GSPATHWAY Activated G-protein coupled receptors stimulate cAMP production and thus activate protein kinase A, involved in a number of signal transduction pathways. ADCY1, GNAS, GNB1, GNGT1, PRKACA, PRKAR1A 6 ADCY1(3), GNAS(4), GNB1(5), PRKAR1A(1) 1281408 13 11 13 2 6 2 2 1 2 0 0.26 0.29 1
8 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(2), IFNG(1), IL12B(2) 572591 5 5 5 0 1 0 2 0 2 0 0.29 0.29 1
9 RABPATHWAY Rab family GTPases regulate vesicle transport, endocytosis and exocytosis, and vesicle docking via interactions with the rabphilins. ACTA1, MEL, RAB11A, RAB1A, RAB2, RAB27A, RAB3A, RAB4A, RAB5A, RAB6A, RAB7, RAB9A 9 ACTA1(3), RAB11A(1), RAB3A(1), RAB5A(1) 819403 6 6 6 0 2 2 0 1 1 0 0.25 0.3 1
10 HSA00130_UBIQUINONE_BIOSYNTHESIS Genes involved in ubiquinone biosynthesis COQ2, COQ3, COQ5, COQ6, COQ7, ND1, ND2, ND3, ND4, ND4L, ND5, ND6, NDUFA12, NDUFA13, NDUFB11 8 COQ2(1), COQ3(1), COQ5(2), COQ6(2), NDUFA12(1), NDUFA13(2) 772198 9 9 9 2 5 1 2 0 1 0 0.53 0.31 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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