Mutation Analysis (MutSig v2.0)
Ovarian Serous Cystadenocarcinoma (Primary solid tumor)
16 April 2014 | analyses__2014_04_16
Maintainer Information
Citation Information
doi:10.7908/C1GM85Z8
Maintained by Dan DiCara (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/C1GM85Z8
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: OV-TP

- Number of patients in set: 316

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:OV-TP.final_analysis_set.maf

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

- Significantly mutated genes (q ≤ 0.1): 6

- Mutations seen in COSMIC: 394

- Significantly mutated genes in COSMIC territory: 39

- Significantly mutated genesets: 30

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

Mutation Preprocessing

- Read 148 MAFs of type "Broad"

- Read 88 MAFs of type "WashU"

- Read 80 MAFs of type "Baylor-SOLiD"

- Total number of mutations in input MAFs: 20219

Mutation Filtering

- Number of mutations before filtering: 20219

- After removing 1 non-mutations: 20218

- After removing 780 mutations outside gene set: 19438

- After removing 9 mutations outside category set: 19429

- After removing 7 "impossible" mutations in

- gene-patient-category bins of zero coverage: 18633

Results
Breakdown of Mutations by Type

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

type | count
--- | ---
Frame_Shift_Del | 441
Frame_Shift_Ins | 155
In_Frame_Del | 148
In_Frame_Ins | 38
Indel | 13
Missense_Mutation | 13160
Nonsense_Mutation | 801
Nonstop_Mutation | 16
Silent | 4231
Splice_Site_Del | 33
Splice_Site_Ins | 5
Splice_Site_SNP | 388
Total | 19429

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 | 1860 | 396631260 | 4.7e-06 | 4.7 | 2.5 | 2.2
*Cp(A/C/T)->T | 2187 | 3659967421 | 6e-07 | 0.6 | 0.32 | 1.7
C->(G/A) | 5207 | 4056598681 | 1.3e-06 | 1.3 | 0.69 | 5
A->mut | 3901 | 4114782770 | 9.5e-07 | 0.95 | 0.51 | 3.8
indel+null | 2031 | 8171381451 | 2.5e-07 | 0.25 | 0.13 | NaN
double_null | 7 | 8171381451 | 8.6e-10 | 0.00086 | 0.00046 | NaN
Total | 15193 | 8171381451 | 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: OV-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: C->(G/A)

- 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: 6. 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 | 401524 | 279 | 276 | 143 | 3 | 47 | 31 | 39 | 61 | 101 | 0 | 1.1e-15 | <1.00e-15 | 0 | 0 | 0 | <1.00e-15 | <1.71e-11
2 | SRC | v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) | 372331 | 4 | 4 | 2 | 0 | 0 | 0 | 4 | 0 | 0 | 0 | 0.0079 | 0.344 | 0.000021 | 0.021 | 4.8e-06 | 6.89e-07 | 0.00590
3 | TBP | TATA box binding protein | 321652 | 4 | 4 | 2 | 0 | 0 | 0 | 0 | 0 | 4 | 0 | 0.00031 | 1.000 | 0.0001 | 1 | 0.0002 | 1.07e-06 | 0.00613
4 | RB1 | retinoblastoma 1 (including osteosarcoma) | 826059 | 9 | 9 | 9 | 0 | 0 | 1 | 3 | 0 | 5 | 0 | 2.5e-06 | 0.334 | 0.24 | 0.68 | 0.4 | 1.46e-05 | 0.0624
5 | PECAM1 | platelet/endothelial cell adhesion molecule (CD31 antigen) | 9588 | 2 | 2 | 2 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0.000032 | 0.638 | NaN | NaN | NaN | 3.15e-05 | 0.0950
6 | GABRA6 | gamma-aminobutyric acid (GABA) A receptor, alpha 6 | 440417 | 6 | 6 | 6 | 1 | 1 | 3 | 1 | 1 | 0 | 0 | 0.000031 | 0.366 | 0.041 | 0.34 | 0.077 | 3.33e-05 | 0.0950
7 | NF1 | neurofibromin 1 (neurofibromatosis, von Recklinghausen disease, Watson disease) | 2619095 | 15 | 14 | 15 | 0 | 1 | 1 | 1 | 3 | 9 | 0 | 0.000021 | 0.0634 | 0.31 | 0.13 | 0.16 | 4.50e-05 | 0.110
8 | BRCA1 | breast cancer 1, early onset | 1798045 | 12 | 12 | 12 | 0 | 0 | 0 | 1 | 0 | 11 | 0 | 7.2e-06 | 0.319 | 0.99 | 0.2 | 0.57 | 5.59e-05 | 0.120
9 | C9orf171 | chromosome 9 open reading frame 171 | 251675 | 5 | 5 | 5 | 0 | 2 | 0 | 2 | 0 | 1 | 0 | 0.00017 | 0.318 | 0.34 | 0.016 | 0.04 | 8.77e-05 | 0.167
10 | CDK12 | cyclin-dependent kinase 12 | 1351667 | 9 | 9 | 9 | 0 | 0 | 0 | 1 | 3 | 5 | 0 | 0.00027 | 0.154 | 0.047 | 0.28 | 0.083 | 0.000261 | 0.424
11 | ARHGEF9 | Cdc42 guanine nucleotide exchange factor (GEF) 9 | 494011 | 5 | 5 | 5 | 0 | 0 | 1 | 2 | 1 | 1 | 0 | 0.0012 | 0.249 | 0.015 | 0.33 | 0.02 | 0.000273 | 0.424
12 | VN1R5 | vomeronasal 1 receptor 5 | 296593 | 4 | 4 | 4 | 0 | 0 | 2 | 1 | 1 | 0 | 0 | 0.00032 | 0.237 | 0.046 | 0.88 | 0.093 | 0.000341 | 0.447
13 | FAT3 | FAT tumor suppressor homolog 3 (Drosophila) | 3706784 | 20 | 19 | 20 | 1 | 4 | 2 | 3 | 10 | 1 | 0 | 0.000035 | 0.0208 | 0.75 | 0.32 | 0.87 | 0.000342 | 0.447
14 | FAM171B | family with sequence similarity 171, member B | 744587 | 7 | 7 | 7 | 0 | 1 | 1 | 2 | 2 | 1 | 0 | 0.000086 | 0.176 | 0.21 | 0.64 | 0.41 | 0.000399 | 0.447
15 | LAIR1 | leukocyte-associated immunoglobulin-like receptor 1 | 267149 | 3 | 3 | 3 | 1 | 0 | 0 | 1 | 1 | 1 | 0 | 0.0065 | 0.842 | 0.039 | 0.015 | 0.006 | 0.000432 | 0.447
16 | SLCO1C1 | solute carrier organic anion transporter family, member 1C1 | 717910 | 6 | 6 | 6 | 0 | 0 | 1 | 4 | 1 | 0 | 0 | 0.00037 | 0.334 | 0.047 | 0.74 | 0.1 | 0.000433 | 0.447
17 | CHST2 | carbohydrate (N-acetylglucosamine-6-O) sulfotransferase 2 | 172127 | 5 | 5 | 5 | 1 | 0 | 2 | 2 | 1 | 0 | 0 | 4e-05 | 0.370 | 1 | 0.98 | 1 | 0.000444 | 0.447
18 | CYP11B1 | cytochrome P450, family 11, subfamily B, polypeptide 1 | 456589 | 7 | 7 | 6 | 0 | 1 | 0 | 3 | 3 | 0 | 0 | 0.000043 | 0.217 | 0.7 | 0.72 | 1 | 0.000473 | 0.447
19 | EFEMP1 | EGF-containing fibulin-like extracellular matrix protein 1 | 475456 | 5 | 5 | 5 | 0 | 1 | 0 | 3 | 0 | 1 | 0 | 0.0011 | 0.464 | 0.26 | 0.015 | 0.041 | 0.000506 | 0.447
20 | GLI2 | GLI-Kruppel family member GLI2 | 947026 | 10 | 9 | 10 | 0 | 2 | 3 | 3 | 1 | 1 | 0 | 0.000081 | 0.0284 | 0.59 | 0.24 | 0.59 | 0.000522 | 0.447
21 | GAS2L1 | growth arrest-specific 2 like 1 | 197396 | 4 | 4 | 4 | 0 | 0 | 0 | 3 | 1 | 0 | 0 | 0.00066 | 0.361 | 0.067 | 0.41 | 0.082 | 0.000587 | 0.478
22 | HAS2 | hyaluronan synthase 2 | 527414 | 5 | 5 | 5 | 0 | 0 | 1 | 3 | 0 | 1 | 0 | 0.00069 | 0.262 | 0.1 | 0.31 | 0.1 | 0.000761 | 0.592
23 | C17orf63 | chromosome 17 open reading frame 63 | 23190 | 2 | 2 | 2 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0.00086 | 0.775 | NaN | NaN | NaN | 0.000857 | 0.623
24 | SMC1A | structural maintenance of chromosomes 1A | 1169859 | 5 | 5 | 5 | 1 | 2 | 0 | 2 | 1 | 0 | 0 | 0.029 | 0.778 | 0.05 | 0.0065 | 0.003 | 0.000899 | 0.623
25 | CREBBP | CREB binding protein (Rubinstein-Taybi syndrome) | 1964764 | 7 | 7 | 7 | 1 | 0 | 1 | 0 | 3 | 3 | 0 | 0.03 | 0.533 | 0.005 | 0.086 | 0.003 | 0.000933 | 0.623
26 | SI | sucrase-isomaltase (alpha-glucosidase) | 1778977 | 10 | 10 | 10 | 0 | 1 | 1 | 4 | 4 | 0 | 0 | 0.0002 | 0.126 | 0.28 | 0.55 | 0.47 | 0.000946 | 0.623
27 | LCOR | ligand dependent nuclear receptor corepressor | 396634 | 4 | 4 | 4 | 0 | 0 | 1 | 1 | 0 | 2 | 0 | 0.0016 | 0.325 | 0.51 | 0.014 | 0.076 | 0.00121 | 0.760
28 | ODAM | odontogenic, ameloblast asssociated | 257049 | 3 | 3 | 3 | 0 | 0 | 0 | 1 | 2 | 0 | 0 | 0.0053 | 0.470 | 0.49 | 0.0059 | 0.023 | 0.00124 | 0.760
29 | OR5D16 | olfactory receptor, family 5, subfamily D, member 16 | 306800 | 4 | 4 | 4 | 0 | 2 | 0 | 1 | 1 | 0 | 0 | 0.00036 | 0.234 | 0.88 | 0.12 | 0.38 | 0.00136 | 0.766
30 | TAS2R1 | taste receptor, type 2, member 1 | 278655 | 3 | 3 | 3 | 0 | 0 | 0 | 2 | 0 | 1 | 0 | 0.0035 | 0.557 | 0.066 | 0.072 | 0.04 | 0.00138 | 0.766
31 | ZNF479 | zinc finger protein 479 | 365518 | 5 | 5 | 5 | 0 | 0 | 2 | 2 | 1 | 0 | 0 | 0.0002 | 0.300 | 0.72 | 0.3 | 0.71 | 0.00141 | 0.766
32 | SLC4A9 | solute carrier family 4, sodium bicarbonate cotransporter, member 9 | 663836 | 3 | 3 | 3 | 0 | 0 | 0 | 1 | 2 | 0 | 0 | 0.075 | 0.500 | 0.0028 | 0.043 | 0.0021 | 0.00154 | 0.766
33 | TRIOBP | TRIO and F-actin binding protein | 1174955 | 8 | 8 | 8 | 0 | 0 | 2 | 4 | 1 | 1 | 0 | 0.0027 | 0.119 | 0.23 | 0.1 | 0.059 | 0.00156 | 0.766
34 | TACC3 | transforming, acidic coiled-coil containing protein 3 | 311979 | 5 | 5 | 5 | 0 | 0 | 1 | 0 | 2 | 2 | 0 | 0.00019 | 0.386 | 0.61 | 0.69 | 0.88 | 0.00162 | 0.766
35 | SLITRK3 | SLIT and NTRK-like family, member 3 | 924753 | 5 | 5 | 5 | 1 | 2 | 0 | 1 | 1 | 1 | 0 | 0.0062 | 0.671 | 0.017 | 0.35 | 0.027 | 0.00163 | 0.766

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: 39. Number of genes displayed: 10

rank | gene | description | n | cos | n_cos | N_cos | cos_ev | p | q
--- | --- | --- | --- | --- | --- | --- | --- | --- | ---
1 | TP53 | tumor protein p53 | 279 | 824 | 278 | 260384 | 70907 | 0 | 0
2 | RB1 | retinoblastoma 1 (including osteosarcoma) | 9 | 267 | 8 | 84372 | 16 | 7.3e-12 | 1.6e-08
3 | NF1 | neurofibromin 1 (neurofibromatosis, von Recklinghausen disease, Watson disease) | 15 | 285 | 6 | 90060 | 8 | 2.7e-08 | 0.000039
4 | MYO3A | myosin IIIA | 7 | 14 | 3 | 4424 | 3 | 9.2e-08 | 0.0001
5 | KLK10 | kallikrein-related peptidase 10 | 2 | 2 | 2 | 632 | 2 | 6.9e-07 | 0.0006
6 | CDC27 | cell division cycle 27 homolog (S. cerevisiae) | 4 | 3 | 2 | 948 | 2 | 1.5e-06 | 0.0011
7 | ERBB2 | v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian) | 4 | 42 | 3 | 13272 | 4 | 2.5e-06 | 0.0015
8 | MLL4 | myeloid/lymphoid or mixed-lineage leukemia 2 | 4 | 6 | 2 | 1896 | 2 | 6.2e-06 | 0.0034
9 | NIPBL | Nipped-B homolog (Drosophila) | 5 | 7 | 2 | 2212 | 2 | 8.4e-06 | 0.0041
10 | FBXW7 | F-box and WD repeat domain containing 7 | 4 | 91 | 3 | 28756 | 118 | 0.000024 | 0.011

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: 30. 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 | HSA04110_CELL_CYCLE | Genes involved in cell cycle | ABL1, ANAPC1, ANAPC10, ANAPC11, ANAPC2, ANAPC4, ANAPC5, ANAPC7, ATM, ATR, BUB1, BUB1B, BUB3, CCNA1, CCNA2, CCNB1, CCNB2, CCNB3, CCND1, CCND2, CCND3, CCNE1, CCNE2, CCNH, CDC14A, CDC14B, CDC16, CDC2, CDC20, CDC23, CDC25A, CDC25B, CDC25C, CDC26, CDC27, CDC45L, CDC6, CDC7, CDK2, CDK4, CDK6, CDK7, CDKN1A, CDKN1B, CDKN1C, CDKN2A, CDKN2B, CDKN2C, CDKN2D, CHEK1, CHEK2, CREBBP, CUL1, DBF4, E2F1, E2F2, E2F3, EP300, ESPL1, FZR1, GADD45A, GADD45B, GADD45G, GSK3B, hCG_1982709, HDAC1, HDAC2, LOC440917, LOC728919, MAD1L1, MAD2L1, MAD2L2, MCM2, MCM3, MCM4, MCM5, MCM6, MCM7, MDM2, ORC1L, ORC2L, ORC3L, ORC4L, ORC5L, ORC6L, PCNA, PKMYT1, PLK1, PRKDC, PTTG1, PTTG2, RB1, RBL1, RBL2, RBX1, SFN, SKP1, SKP2, SMAD2, SMAD3, SMAD4, SMC1A, SMC1B, TFDP1, TGFB1, TGFB2, TGFB3, TP53, WEE1, YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ, YWHAZ | 106 | ABL1(1), ANAPC1(1), ANAPC2(1), ANAPC4(1), ANAPC5(1), ATM(5), ATR(2), BUB1(1), BUB1B(2), BUB3(1), CCNA1(2), CCNA2(1), CCNB3(3), CCNH(1), CDC20(1), CDC25B(2), CDC27(4), CDC6(1), CDC7(2), CDK2(1), CDKN1A(1), CDKN1B(1), CDKN2C(2), CDKN2D(1), CHEK2(1), CREBBP(7), E2F2(1), EP300(1), GADD45A(1), GADD45B(1), GSK3B(1), HDAC1(1), MAD2L2(1), MCM2(2), MCM3(1), MCM4(2), MCM5(2), ORC1L(1), ORC4L(1), PRKDC(8), RB1(9), RBL1(1), RBL2(3), SKP2(2), SMC1A(5), SMC1B(3), TFDP1(2), TP53(279), YWHAB(1), YWHAE(2), YWHAG(2) | 59044600 | 380 | 287 | 244 | 28 | 60 | 44 | 71 | 84 | 121 | 0 | 2.00e-15 | <1.00e-15 | <5.13e-14
2 | 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(1), ATM(5), BUB1(1), BUB1B(2), BUB3(1), CCNA1(2), CCNA2(1), CCNB3(3), CCNH(1), CDAN1(2), CDC20(1), CDC25B(2), CDC6(1), CDC7(2), CDH1(2), CDK2(1), CDKN1A(1), CHEK2(1), E2F2(1), E2F5(1), EP300(1), GADD45A(1), GSK3B(1), HDAC1(1), HDAC3(2), HDAC4(2), HDAC5(1), HDAC6(2), MAD2L2(1), MCM2(2), MCM3(1), MCM4(2), MCM5(2), MPEG1(1), ORC1L(1), ORC4L(1), PRKDC(8), RB1(9), RBL1(1), SKP2(2), TBC1D8(3), TFDP1(2), TP53(279) | 48735694 | 358 | 283 | 222 | 27 | 56 | 42 | 65 | 80 | 115 | 0 | 1.33e-15 | <1.00e-15 | <5.13e-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 | EGFR(7), IGF1R(1), PPP2CA(2), PRKCA(1), RB1(9), TEP1(5), TERF1(1), TERT(1), TNKS(1), TP53(279) | 12360237 | 307 | 281 | 171 | 10 | 50 | 33 | 49 | 65 | 110 | 0 | <1.00e-15 | <1.00e-15 | <5.13e-14
4 | APOPTOSIS_GENMAPP |  | APAF1, BAK1, BCL2L7P1, BAX, BCL2, BCL2L1, BID, BIRC2, BIRC3, BIRC4, CASP2, CASP3, CASP6, CASP7, CASP8, CASP9, CYCS, FADD, FAS, FASLG, GZMB, IKBKG, JUN, MAP2K4, MAP3K1, MAP3K14, MAPK10, MCL1, MDM2, MYC, NFKB1, NFKBIA, PARP1, PRF1, RELA, RIPK1, TNF, TNFRSF1A, TNFRSF1B, TNFSF10, TP53, TRADD, TRAF1, TRAF2 | 40 | APAF1(2), BAK1(1), BID(1), BIRC3(2), CASP2(1), CASP6(1), CASP7(1), CASP9(1), FADD(1), MAP2K4(1), MAP3K1(1), MAP3K14(1), NFKB1(1), PRF1(2), RELA(1), TNF(1), TNFRSF1A(1), TNFSF10(1), TP53(279), TRAF1(4), TRAF2(1) | 16033981 | 305 | 280 | 169 | 10 | 50 | 36 | 48 | 67 | 104 | 0 | <1.00e-15 | <1.00e-15 | <5.13e-14
5 | ATRBRCAPATHWAY | BRCA1 and 2 block cell cycle progression in response to DNA damage and promote double-stranded break repair; mutations induce breast cancer susceptibility. | ATM, ATR, BRCA1, BRCA2, CHEK1, CHEK2, FANCA, FANCC, FANCD2, FANCE, FANCF, FANCG, HUS1, MRE11A, NBS1, RAD1, RAD17, RAD50, RAD51, RAD9A, TP53, TREX1 | 21 | ATM(5), ATR(2), BRCA1(12), BRCA2(11), CHEK2(1), FANCA(3), FANCC(2), FANCD2(1), FANCE(1), FANCG(1), HUS1(1), RAD1(1), RAD50(2), RAD51(1), TP53(279) | 19936305 | 323 | 280 | 187 | 6 | 49 | 33 | 47 | 69 | 124 | 1 | <1.00e-15 | <1.00e-15 | <5.13e-14
6 | 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(5), CDC25B(2), CDK2(1), MYT1(2), RB1(9), TP53(279) | 7986534 | 298 | 279 | 162 | 5 | 47 | 33 | 47 | 64 | 107 | 0 | <1.00e-15 | <1.00e-15 | <5.13e-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 | CDK2(1), CDKN1A(1), CDKN1B(1), E2F2(1), NXT1(1), PRB1(1), TP53(279) | 3310452 | 285 | 279 | 149 | 8 | 49 | 33 | 40 | 62 | 101 | 0 | <1.00e-15 | <1.00e-15 | <5.13e-14
8 | 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(2), ATM(5), CDK2(1), CDKN1A(1), GADD45A(1), RB1(9), TP53(279) | 8056664 | 298 | 278 | 162 | 3 | 48 | 34 | 44 | 65 | 107 | 0 | <1.00e-15 | <1.00e-15 | <5.13e-14
9 | ST_JNK_MAPK_PATHWAY | JNKs are MAP kinases regulated by several levels of kinases (MAPKK, MAPKKK) and phosphorylate transcription factors and regulatory proteins. | AKT1, ATF2, CDC42, DLD, DUSP10, DUSP4, DUSP8, GAB1, GADD45A, GCK, IL1R1, JUN, MAP2K4, MAP2K5, MAP2K7, MAP3K1, MAP3K10, MAP3K11, MAP3K12, MAP3K13, MAP3K2, MAP3K3, MAP3K4, MAP3K5, MAP3K7, MAP3K7IP1, MAP3K7IP2, MAP3K9, MAPK10, MAPK7, MAPK8, MAPK9, MYEF2, NFATC3, NR2C2, PAPPA, SHC1, TP53, TRAF6, ZAK | 36 | GADD45A(1), MAP2K4(1), MAP3K1(1), MAP3K10(2), MAP3K12(1), MAP3K13(2), MAP3K2(2), MAP3K3(1), MAP3K4(2), MAP3K5(2), MAP3K7(3), MAP3K9(1), MAPK8(1), MAPK9(1), MYEF2(1), PAPPA(3), SHC1(1), TP53(279), TRAF6(2) | 21375636 | 307 | 278 | 171 | 6 | 51 | 37 | 50 | 65 | 104 | 0 | <1.00e-15 | <1.00e-15 | <5.13e-14
10 | 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 | 17 | DNAJA3(2), IKBKB(1), JAK2(2), LIN7A(1), NFKB1(1), RB1(9), RELA(1), TNF(1), TNFRSF1A(1), TP53(279), USH1C(1) | 7976204 | 299 | 278 | 163 | 5 | 49 | 35 | 45 | 63 | 107 | 0 | <1.00e-15 | <1.00e-15 | <5.13e-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 | FXRPATHWAY | The nuclear receptor transcription factors FXR and LXR are activated by cholesterol metabolites and regulate cholesterol homeostasis. | FABP6, LDLR, NR0B2, NR1H3, NR1H4, RXRA | 6 | LDLR(3), NR1H3(4), NR1H4(3), RXRA(2) | 2264708 | 12 | 12 | 12 | 0 | 2 | 2 | 3 | 2 | 3 | 0 | 0.025 | 0.00088 | 0.54
2 | HSA00902_MONOTERPENOID_BIOSYNTHESIS | Genes involved in monoterpenoid biosynthesis | CYP2C19, CYP2C9 | 2 | CYP2C19(4), CYP2C9(1) | 942461 | 5 | 5 | 5 | 1 | 0 | 0 | 1 | 4 | 0 | 0 | 0.6 | 0.028 | 1
3 | HSA00533_KERATAN_SULFATE_BIOSYNTHESIS | Genes involved in keratan sulfate biosynthesis | B3GNT1, B3GNT2, B3GNT7, B4GALT1, B4GALT2, B4GALT3, B4GALT4, CHST1, CHST2, CHST4, CHST6, FUT8, ST3GAL1, ST3GAL2, ST3GAL3, ST3GAL4 | 16 | B3GNT2(1), B3GNT7(1), B4GALT2(1), CHST2(5), CHST6(1), FUT8(1), ST3GAL2(2), ST3GAL3(3) | 4877454 | 15 | 15 | 15 | 1 | 4 | 3 | 3 | 4 | 1 | 0 | 0.053 | 0.043 | 1
4 | FOLATE_BIOSYNTHESIS |  | ALPI, ALPL, ALPP, ALPP, ALPPL2, ALPPL2, DHFR, FPGS, GCH1, GGH, SPR | 9 | ALPL(2), ALPP(2), FPGS(1), SPR(2) | 2149074 | 7 | 7 | 7 | 0 | 2 | 4 | 0 | 0 | 1 | 0 | 0.04 | 0.056 | 1
5 | AMIPATHWAY | Endogenous anti-thrombosis pathways are overwhelmed in plaque-narrowed blood vessels, resulting in potentially lethal myocardial infarction. | ADCY1, CD3D, CD3E, CD3G, CD3Z, CD4, CREBBP, CSK, GNAS, GNB1, GNGT1, HLA-DRA, HLA-DRB1, LCK, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PTPRC, TRA@, TRB@, ZAP70 | 21 | ADCY1(4), CD3E(2), CD4(1), CREBBP(7), CSK(1), GNAS(3), HLA-DRA(1), HLA-DRB1(1), LCK(1), PRKACG(1), PRKAR2A(1), PRKAR2B(1), PTPRC(3), ZAP70(1) | 9488232 | 28 | 28 | 27 | 3 | 5 | 3 | 6 | 6 | 8 | 0 | 0.062 | 0.066 | 1
6 | CSKPATHWAY | Csk inhibits T-cell activation by phosphorylating Lck; Csk is regulated by cAMP-dependent kinases and is opposed by the T-cell activator CD45. | ADCY1, CD3D, CD3E, CD3G, CD3Z, CD4, CREBBP, CSK, GNAS, GNB1, GNGT1, HLA-DRA, HLA-DRB1, LCK, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PTPRC, TRA@, TRB@, ZAP70 | 21 | ADCY1(4), CD3E(2), CD4(1), CREBBP(7), CSK(1), GNAS(3), HLA-DRA(1), HLA-DRB1(1), LCK(1), PRKACG(1), PRKAR2A(1), PRKAR2B(1), PTPRC(3), ZAP70(1) | 9488232 | 28 | 28 | 27 | 3 | 5 | 3 | 6 | 6 | 8 | 0 | 0.062 | 0.066 | 1
7 | LYSINE_BIOSYNTHESIS |  | AADAT, AASDH, AASDHPPT, AASS, KARS | 5 | AASDH(5), AASDHPPT(1), AASS(2), KARS(1) | 3198163 | 9 | 9 | 9 | 1 | 0 | 0 | 3 | 4 | 2 | 0 | 0.39 | 0.075 | 1
8 | HSA00601_GLYCOSPHINGOLIPID_BIOSYNTHESIS_LACTOSERIES | Genes involved in glycosphingolipid biosynthesis - lactoseries | ABO, B3GALT1, B3GALT2, B3GALT5, B3GNT5, FUT1, FUT2, FUT3, ST3GAL3, ST3GAL4 | 10 | ABO(1), B3GALT1(1), B3GALT2(2), B3GNT5(1), FUT1(1), ST3GAL3(3) | 3040139 | 9 | 9 | 9 | 1 | 3 | 1 | 3 | 0 | 2 | 0 | 0.2 | 0.078 | 1
9 | HSA00750_VITAMIN_B6_METABOLISM | Genes involved in vitamin B6 metabolism | AOX1, PDXK, PDXP, PNPO, PSAT1 | 5 | AOX1(4), PDXK(1), PDXP(1), PSAT1(1) | 2140556 | 7 | 7 | 7 | 1 | 0 | 1 | 3 | 2 | 1 | 0 | 0.49 | 0.078 | 1
10 | SETPATHWAY | Cytotoxic T cells release perforin, which to allow entry into target cells of granzyme B, which activates caspases, and granzyme A, which induces caspase-independent apoptosis. | ANP32A, APEX1, CREBBP, DFFA, DFFB, GZMA, GZMB, HMGB2, NME1, PRF1, SET | 11 | APEX1(2), CREBBP(7), GZMA(2), PRF1(2) | 4460489 | 13 | 13 | 13 | 2 | 2 | 1 | 0 | 5 | 5 | 0 | 0.37 | 0.091 | 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.

- Analysis Results (MD5 checksum)

- Auxiliary Data (MD5 checksum)

- MAGE-TAB File (MD5 checksum)

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