Mutation Analysis (MutSig v2.0)
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (Primary solid tumor)
23 September 2013 | analyses__2013_09_23
Maintainer Information
Citation Information
doi:10.7908/C1M906ZS
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/C1M906ZS
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: CESC-TP

- Number of patients in set: 39

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:CESC-TP.final_analysis_set.maf

- Significantly mutated genes (q ≤ 0.1): 14

- Mutations seen in COSMIC: 38

- Significantly mutated genes in COSMIC territory: 2

- Genes with clustered mutations (≤ 3 aa apart): 76

- Significantly mutated genesets: 0

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

Mutation Preprocessing

- Read 39 MAFs of type "Broad"

- Total number of mutations in input MAFs: 10020

- After removing 5 mutations outside chr1-24: 10015

- After removing 781 noncoding mutations: 9234

Mutation Filtering

- Number of mutations before filtering: 9234

- After removing 153 mutations outside gene set: 9081

- After removing 21 mutations outside category set: 9060

Results
Breakdown of Mutations by Type

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

type | count
--- | ---
Frame_Shift_Del | 117
Frame_Shift_Ins | 68
In_Frame_Del | 58
In_Frame_Ins | 18
Missense_Mutation | 5653
Nonsense_Mutation | 474
Nonstop_Mutation | 11
Silent | 2551
Splice_Site | 97
Translation_Start_Site | 13
Total | 9060

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) | 3540 | 150569812 | 0.000024 | 24 | 4.1 | 3
(A/C/G)p*C->(T/G) | 1145 | 425623126 | 2.7e-06 | 2.7 | 0.47 | 2.7
C->A | 351 | 576192938 | 6.1e-07 | 0.61 | 0.11 | 4.4
A->mut | 630 | 556925266 | 1.1e-06 | 1.1 | 0.2 | 3.9
indel+null | 824 | 1133118204 | 7.3e-07 | 0.73 | 0.13 | NaN
double_null | 19 | 1133118204 | 1.7e-08 | 0.017 | 0.0029 | NaN
Total | 6509 | 1133118204 | 5.7e-06 | 5.7 | 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: CESC-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: (A/C/G)p*C->(T/G)

- n3 = number of nonsilent mutations of type: C->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: 14. Number of genes displayed: 35. Click on a gene name to display its stick figure depicting the distribution of mutations and mutation types across the chosen gene (this feature may not be available for all significant genes).

rank | gene | description | N | n | npat | nsite | nsil | n1 | n2 | n3 | n4 | n5 | n6 | p_classic | p_ns_s | p_clust | p_cons | p_joint | p | q
--- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | ---
1 | PIK3CA | phosphoinositide-3-kinase, catalytic, alpha polypeptide | 126650 | 11 | 9 | 4 | 0 | 10 | 0 | 0 | 1 | 0 | 0 | 3.6e-08 | 0.12 | 8e-06 | 0.017 | 0 | <1.00e-15 | <9.02e-12
2 | PRSS48 | protease, serine, 48 | 38982 | 16 | 2 | 9 | 3 | 0 | 3 | 2 | 9 | 2 | 0 | 0.0073 | 0.32 | 0 | 0.96 | 0 | <1.00e-15 | <9.02e-12
3 | TMCC1 | transmembrane and coiled-coil domain family 1 | 77000 | 4 | 4 | 3 | 0 | 0 | 0 | 1 | 0 | 3 | 0 | 0.00014 | 0.82 | 0.00013 | 0.086 | 9e-05 | 2.35e-07 | 0.00121
4 | PRG4 | proteoglycan 4 | 166081 | 15 | 5 | 12 | 0 | 2 | 1 | 1 | 1 | 10 | 0 | 0.0004 | 0.32 | 0.000036 | 0.4 | 0.000036 | 2.68e-07 | 0.00121
5 | CDC27 | cell division cycle 27 homolog (S. cerevisiae) | 97176 | 7 | 5 | 4 | 0 | 0 | 0 | 1 | 3 | 3 | 0 | 0.000024 | 0.37 | 0.0079 | 0.044 | 0.0091 | 3.49e-06 | 0.0126
6 | UGT2B10 | UDP glucuronosyltransferase 2 family, polypeptide B10 | 122318 | 20 | 3 | 14 | 3 | 2 | 3 | 2 | 13 | 0 | 0 | 0.074 | 0.23 | 2e-07 | 0.99 | 5.6e-06 | 6.48e-06 | 0.0178
7 | NFE2L2 | nuclear factor (erythroid-derived 2)-like 2 | 69545 | 7 | 6 | 6 | 0 | 4 | 0 | 0 | 1 | 2 | 0 | 2.8e-06 | 0.34 | 0.49 | 0.041 | 0.16 | 6.90e-06 | 0.0178
8 | MAPK1 | mitogen-activated protein kinase 1 | 38660 | 3 | 3 | 1 | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 0.0011 | 0.41 | 0.00032 | 0.19 | 0.00065 | 1.08e-05 | 0.0243
9 | PTH2 | parathyroid hormone 2 | 8040 | 2 | 2 | 2 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0.000051 | 0.38 | 0.7 | 0.048 | 0.028 | 2.02e-05 | 0.0405
10 | UGT3A2 | UDP glycosyltransferase 3 family, polypeptide A2 | 62290 | 3 | 3 | 2 | 0 | 1 | 0 | 0 | 0 | 2 | 0 | 0.0033 | 0.69 | 0.016 | 0.0019 | 0.00059 | 2.78e-05 | 0.0502
11 | NFYB | nuclear transcription factor Y, beta | 25367 | 2 | 2 | 1 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0.00083 | 0.55 | 0.054 | 0.0017 | 0.0038 | 4.33e-05 | 0.0687
12 | SAA2 | serum amyloid A2 | 14856 | 4 | 2 | 2 | 0 | 2 | 0 | 0 | 2 | 0 | 0 | 0.0018 | 0.36 | 0.00085 | 0.99 | 0.0018 | 4.57e-05 | 0.0687
13 | SSX7 | synovial sarcoma, X breakpoint 7 | 23049 | 5 | 3 | 4 | 0 | 0 | 2 | 1 | 2 | 0 | 0 | 0.000081 | 0.34 | 0.043 | 1 | 0.058 | 6.28e-05 | 0.0871
14 | PRB2 | proline-rich protein BstNI subfamily 2 | 49240 | 6 | 4 | 5 | 0 | 0 | 0 | 0 | 1 | 5 | 0 | 0.000011 | 0.52 | 0.47 | 0.29 | 0.53 | 7.59e-05 | 0.0978
15 | ABCF1 | ATP-binding cassette, sub-family F (GCN20), member 1 | 99449 | 4 | 2 | 2 | 0 | 0 | 4 | 0 | 0 | 0 | 0 | 0.082 | 0.26 | 0.000034 | 1 | 0.000083 | 8.76e-05 | 0.105
16 | RAET1L | retinoic acid early transcript 1L | 25451 | 5 | 2 | 4 | 0 | 1 | 1 | 0 | 3 | 0 | 0 | 0.0052 | 0.28 | 0.00047 | 0.45 | 0.0021 | 0.000135 | 0.152
17 | ITGAX | integrin, alpha X (complement component 3 receptor 4 subunit) | 131027 | 8 | 4 | 6 | 6 | 2 | 2 | 0 | 3 | 1 | 0 | 0.2 | 0.96 | 0.000038 | 0.52 | 0.00012 | 0.000282 | 0.289
18 | PLAC4 | placenta-specific 4 | 7160 | 2 | 2 | 2 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0.00014 | 1 | 0.82 | 0.058 | 0.18 | 0.000295 | 0.289
19 | ARID1A | AT rich interactive domain 1A (SWI-like) | 226053 | 7 | 6 | 6 | 0 | 1 | 1 | 0 | 0 | 3 | 2 | 0.000026 | 0.29 | 0.77 | 0.5 | 1 | 0.000304 | 0.289
20 | PTEN | phosphatase and tensin homolog (mutated in multiple advanced cancers 1) | 45935 | 3 | 3 | 3 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 0.000088 | 0.59 | 0.28 | 0.82 | 0.39 | 0.000388 | 0.350
21 | POU4F1 | POU class 4 homeobox 1 | 22119 | 3 | 3 | 2 | 0 | 1 | 0 | 0 | 0 | 2 | 0 | 0.000072 | 0.66 | 0.37 | 0.78 | 0.5 | 0.000408 | 0.350
22 | FCRL1 | Fc receptor-like 1 | 53853 | 3 | 3 | 3 | 0 | 1 | 0 | 0 | 2 | 0 | 0 | 0.00042 | 0.45 | 0.033 | 0.67 | 0.092 | 0.000430 | 0.353
23 | AQP2 | aquaporin 2 (collecting duct) | 29453 | 3 | 3 | 3 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 0.000098 | 0.33 | 0.48 | 0.15 | 0.45 | 0.000486 | 0.381
24 | FAM49A | family with sequence similarity 49, member A | 39076 | 2 | 2 | 2 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0.002 | 0.61 | 0.015 | 0.54 | 0.026 | 0.000555 | 0.417
25 | TIE1 | tyrosine kinase with immunoglobulin-like and EGF-like domains 1 | 125328 | 4 | 3 | 4 | 0 | 0 | 2 | 1 | 0 | 1 | 0 | 0.004 | 0.29 | 0.066 | 0.03 | 0.016 | 0.000665 | 0.480
26 | ZNF645 | zinc finger protein 645 | 49998 | 2 | 2 | 1 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0.0044 | 0.65 | 0.013 | 0.063 | 0.015 | 0.000694 | 0.481
27 | USP26 | ubiquitin specific peptidase 26 | 107055 | 2 | 2 | 2 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0.027 | 0.7 | 0.045 | 0.0051 | 0.0026 | 0.000730 | 0.487
28 | OR10G8 | olfactory receptor, family 10, subfamily G, member 8 | 36617 | 18 | 2 | 12 | 15 | 0 | 10 | 0 | 7 | 1 | 0 | 1 | 0.99 | 0.000018 | 1 | 0.000072 | 0.000757 | 0.487
29 | LYZL1 | lysozyme-like 1 | 22057 | 3 | 3 | 3 | 0 | 1 | 1 | 0 | 0 | 1 | 0 | 0.00014 | 0.36 | 0.68 | 0.4 | 0.57 | 0.000804 | 0.495
30 | CPNE3 | copine III | 64568 | 3 | 2 | 3 | 0 | 2 | 0 | 0 | 0 | 1 | 0 | 0.042 | 0.51 | 0.00072 | 0.97 | 0.0019 | 0.000823 | 0.495
31 | FETUB | fetuin B | 45815 | 2 | 2 | 2 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0.01 | 0.6 | 0.088 | 0.024 | 0.0085 | 0.000917 | 0.533
32 | GPR153 | G protein-coupled receptor 153 | 40937 | 2 | 2 | 2 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0.0021 | 0.59 | 0.21 | 0.084 | 0.043 | 0.000947 | 0.533
33 | ERP27 | endoplasmic reticulum protein 27 kDa | 32955 | 3 | 3 | 3 | 0 | 0 | 2 | 0 | 1 | 0 | 0 | 0.0002 | 0.46 | 0.28 | 0.64 | 0.48 | 0.00101 | 0.535
34 | SSX3 | synovial sarcoma, X breakpoint 3 | 25038 | 6 | 2 | 4 | 1 | 0 | 6 | 0 | 0 | 0 | 0 | 0.0056 | 0.51 | 0.017 | 0.24 | 0.018 | 0.00101 | 0.535
35 | ZNF563 | zinc finger protein 563 | 56133 | 3 | 3 | 2 | 0 | 1 | 0 | 0 | 2 | 0 | 0 | 0.0024 | 0.52 | 0.0061 | 0.99 | 0.046 | 0.00111 | 0.573

PIK3CA

Figure S1. This figure depicts the distribution of mutations and mutation types across the PIK3CA significant gene.

PRSS48

Figure S2. This figure depicts the distribution of mutations and mutation types across the PRSS48 significant gene.

TMCC1

Figure S3. This figure depicts the distribution of mutations and mutation types across the TMCC1 significant gene.

PRG4

Figure S4. This figure depicts the distribution of mutations and mutation types across the PRG4 significant gene.

CDC27

Figure S5. This figure depicts the distribution of mutations and mutation types across the CDC27 significant gene.

UGT2B10

Figure S6. This figure depicts the distribution of mutations and mutation types across the UGT2B10 significant gene.

NFE2L2

Figure S7. This figure depicts the distribution of mutations and mutation types across the NFE2L2 significant gene.

MAPK1

Figure S8. This figure depicts the distribution of mutations and mutation types across the MAPK1 significant gene.

UGT3A2

Figure S9. This figure depicts the distribution of mutations and mutation types across the UGT3A2 significant gene.

NFYB

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

SAA2

Figure S11. This figure depicts the distribution of mutations and mutation types across the SAA2 significant gene.

SSX7

Figure S12. This figure depicts the distribution of mutations and mutation types across the SSX7 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: 2. Number of genes displayed: 10

rank | gene | description | n | cos | n_cos | N_cos | cos_ev | p | q
--- | --- | --- | --- | --- | --- | --- | --- | --- | ---
1 | PIK3CA | phosphoinositide-3-kinase, catalytic, alpha polypeptide | 11 | 220 | 8 | 8580 | 3939 | 0 | 0
2 | CHEK2 | CHK2 checkpoint homolog (S. pombe) | 2 | 2 | 2 | 78 | 2 | 9.9e-08 | 0.00022
3 | ATL2 | atlastin GTPase 2 | 1 | 1 | 1 | 39 | 1 | 0.00022 | 0.13
4 | EDA | ectodysplasin A | 1 | 1 | 1 | 39 | 1 | 0.00022 | 0.13
5 | KIAA1024 | KIAA1024 | 2 | 1 | 1 | 39 | 1 | 0.00022 | 0.13
6 | KRTAP5-5 | keratin associated protein 5-5 | 2 | 1 | 1 | 39 | 1 | 0.00022 | 0.13
7 | MAPK11 | mitogen-activated protein kinase 11 | 1 | 1 | 1 | 39 | 1 | 0.00022 | 0.13
8 | SUV39H2 | suppressor of variegation 3-9 homolog 2 (Drosophila) | 1 | 1 | 1 | 39 | 2 | 0.00022 | 0.13
9 | ALS2 | amyotrophic lateral sclerosis 2 (juvenile) | 2 | 3 | 1 | 117 | 1 | 0.00067 | 0.2
10 | EPHA10 | EPH receptor A10 | 1 | 3 | 1 | 117 | 1 | 0.00067 | 0.2

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
--- | --- | --- | --- | --- | --- | --- | --- | --- | --- | ---
2867 | PIK3CA | phosphoinositide-3-kinase, catalytic, alpha polypeptide | 11 | 0 | 14 | 24 | 24 | 14 | 24 | 24
4425 | ZSCAN5A | zinc finger and SCAN domain containing 5A | 39 | 0 | 12 | 31 | 61 | 12 | 31 | 61
2636 | OR1S2 | olfactory receptor, family 1, subfamily S, member 2 | 33 | 0 | 11 | 27 | 39 | 11 | 27 | 39
2635 | OR1S1 | olfactory receptor, family 1, subfamily S, member 1 | 32 | 0 | 11 | 21 | 45 | 11 | 21 | 45
2205 | MAGEA12 | melanoma antigen family A, 12 | 29 | 0 | 10 | 26 | 44 | 10 | 26 | 44
3051 | PRSS48 | protease, serine, 48 | 16 | 0 | 6 | 22 | 54 | 6 | 22 | 54
2625 | OR10G8 | olfactory receptor, family 10, subfamily G, member 8 | 18 | 0 | 5 | 5 | 13 | 5 | 5 | 13
1781 | IFITM2 | interferon induced transmembrane protein 2 (1-8D) | 9 | 0 | 3 | 3 | 5 | 3 | 3 | 5
2240 | MAPK1 | mitogen-activated protein kinase 1 | 3 | 0 | 3 | 3 | 3 | 3 | 3 | 3
4426 | ZSCAN5B | zinc finger and SCAN domain containing 5B | 16 | 0 | 2 | 9 | 13 | 2 | 9 | 13

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: 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 | PAR1PATHWAY | Activated extracellular thrombin cleaves and activates the G-protein coupled receptors PAR1 and PAR4, which activate platelets. | ADCY1, ARHA, ARHGEF1, F2, F2R, F2RL3, GNA12, GNA13, GNAI1, GNAQ, GNB1, GNGT1, MAP3K7, PIK3CA, PIK3R1, PLCB1, PPP1R12B, PRKCA, PRKCB1, PTK2B, ROCK1 | 19 | ADCY1(1), ARHGEF1(1), F2R(1), F2RL3(2), GNA13(1), PIK3CA(11), PIK3R1(1), PPP1R12B(1), PRKCA(1), ROCK1(3) | 1478575 | 23 | 13 | 16 | 1 | 16 | 3 | 1 | 2 | 0 | 1 | 0.011 | 0.00052 | 0.15
2 | ACHPATHWAY | Nicotinic acetylcholine receptors are ligand-gated ion channels that primarily mediate neuromuscular signaling and may inhibit neuronal apoptosis via the AKT pathway. | AKT1, BAD, CHRNB1, CHRNG, FOXO3A, MUSK, PIK3CA, PIK3R1, PTK2, PTK2B, RAPSN, SRC, TERT, TNFSF6, YWHAH | 13 | CHRNG(1), MUSK(1), PIK3CA(11), PIK3R1(1), PTK2(1) | 935251 | 15 | 11 | 8 | 1 | 11 | 0 | 1 | 2 | 1 | 0 | 0.053 | 0.00053 | 0.15
3 | ERK5PATHWAY | Signaling between a tissue and its innervating axon stimulates retrograde transport via Trk receptors, which activate Erk5, which induces transcription of anti-apoptotic factors. | AKT1, CREB1, GRB2, HRAS, MAPK1, MAPK3, MAPK7, MEF2A, MEF2B, MEF2C, MEF2D, NTRK1, PIK3CA, PIK3R1, PLCG1, RPS6KA1, SHC1 | 17 | MAPK1(3), MAPK7(1), MEF2C(1), PIK3CA(11), PIK3R1(1), RPS6KA1(2) | 1088110 | 19 | 11 | 10 | 1 | 14 | 1 | 0 | 3 | 1 | 0 | 0.03 | 0.00085 | 0.15
4 | GCRPATHWAY | Corticosteroids activate the glucocorticoid receptor (GR), which inhibits NF-kB and activates Annexin-1, thus inhibiting the inflammatory response. | ADRB2, AKT1, ANXA1, CALM1, CALM2, CALM3, CRN, GNAS, GNB1, GNGT1, HSPCA, NFKB1, NOS3, NPPA, NR3C1, PIK3CA, PIK3R1, RELA, SYT1 | 17 | CALM1(1), CALM3(1), NPPA(1), PIK3CA(11), PIK3R1(1), SYT1(1) | 1019231 | 16 | 11 | 9 | 0 | 12 | 1 | 1 | 2 | 0 | 0 | 0.018 | 0.00096 | 0.15
5 | CTLA4PATHWAY | T cell activation requires interaction with an antigen-MHC-I complex on an antigen-presenting cell (APC), as well as CD28 interaction with the APC's CD80 or 86. | CD28, CD3D, CD3E, CD3G, CD3Z, CD80, CD86, CTLA4, GRB2, HLA-DRA, HLA-DRB1, ICOS, ICOSL, IL2, ITK, LCK, PIK3CA, PIK3R1, PTPN11, TRA@, TRB@ | 17 | CD86(1), ITK(1), PIK3CA(11), PIK3R1(1), PTPN11(1) | 739491 | 15 | 9 | 8 | 0 | 12 | 1 | 0 | 2 | 0 | 0 | 0.018 | 0.0017 | 0.18
6 | PTENPATHWAY | PTEN suppresses AKT-induced cell proliferation and antagonizes the action of PI3K. | AKT1, BCAR1, CDKN1B, FOXO3A, GRB2, ILK, ITGB1, MAPK1, MAPK3, PDK2, PDPK1, PIK3CA, PIK3R1, PTEN, PTK2, SHC1, SOS1, TNFSF6 | 16 | MAPK1(3), PIK3CA(11), PIK3R1(1), PTEN(3), PTK2(1), SOS1(1) | 1108069 | 20 | 11 | 11 | 0 | 15 | 0 | 0 | 2 | 3 | 0 | 0.0079 | 0.0019 | 0.18
7 | ST_TYPE_I_INTERFERON_PATHWAY | Type I interferon is an antiviral cytokine that induces a JAK-STAT type pathway leading to ISGF3 activation and a cellular antiviral response. | IFNAR1, IFNB1, ISGF3G, JAK1, PTPRU, REG1A, STAT1, STAT2, TYK2 | 8 | IFNAR1(2), PTPRU(1), REG1A(1), STAT1(3), TYK2(3) | 723179 | 10 | 10 | 10 | 1 | 7 | 3 | 0 | 0 | 0 | 0 | 0.12 | 0.002 | 0.18
8 | IFNGPATHWAY | IFN gamma signaling pathway | IFNG, IFNGR1, IFNGR2, JAK1, JAK2, STAT1 | 6 | IFNGR1(2), IFNGR2(2), JAK2(1), STAT1(3) | 473117 | 8 | 7 | 8 | 1 | 4 | 1 | 0 | 0 | 3 | 0 | 0.48 | 0.0026 | 0.2
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(1), PIK3CA(11), PIK3R1(1), POLR1A(2), POLR1C(2), TP53(2) | 1168503 | 19 | 14 | 12 | 2 | 13 | 0 | 0 | 4 | 2 | 0 | 0.13 | 0.0034 | 0.21
10 | 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 | 7 | PIK3CA(11), PIK3R1(1), PRKCA(1) | 739813 | 13 | 9 | 6 | 1 | 11 | 0 | 0 | 2 | 0 | 0 | 0.13 | 0.0034 | 0.21

Table 7. 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 | ST_TYPE_I_INTERFERON_PATHWAY | Type I interferon is an antiviral cytokine that induces a JAK-STAT type pathway leading to ISGF3 activation and a cellular antiviral response. | IFNAR1, IFNB1, ISGF3G, JAK1, PTPRU, REG1A, STAT1, STAT2, TYK2 | 8 | IFNAR1(2), PTPRU(1), REG1A(1), STAT1(3), TYK2(3) | 723179 | 10 | 10 | 10 | 1 | 7 | 3 | 0 | 0 | 0 | 0 | 0.12 | 0.002 | 0.79
2 | IFNGPATHWAY | IFN gamma signaling pathway | IFNG, IFNGR1, IFNGR2, JAK1, JAK2, STAT1 | 6 | IFNGR1(2), IFNGR2(2), JAK2(1), STAT1(3) | 473117 | 8 | 7 | 8 | 1 | 4 | 1 | 0 | 0 | 3 | 0 | 0.48 | 0.0026 | 0.79
3 | IFNAPATHWAY | Interferon alpha, active in the immune response, binds to the IFN receptor and activates Jak1 and Tyk2, which phosphorylate Stat1 and Stat2. | IFNA1, IFNAR1, IFNAR2, IFNB1, ISGF3G, JAK1, STAT1, STAT2, TYK2 | 8 | IFNA1(1), IFNAR1(2), IFNAR2(1), STAT1(3), TYK2(3) | 627650 | 10 | 9 | 10 | 1 | 9 | 1 | 0 | 0 | 0 | 0 | 0.14 | 0.011 | 1
4 | FIBRINOLYSISPATHWAY | Thrombin cleavage of fibrinogen results in rapid formation of fibrin threads that form a mesh to capture platelets and other blood cells into a clot. | CPB2, F13A1, F2, F2R, FGA, FGB, FGG, PLAT, PLAU, PLG, SERPINB2, SERPINE1 | 12 | CPB2(2), F2R(1), FGA(1), PLAU(1), PLG(2) | 774038 | 7 | 7 | 7 | 1 | 3 | 1 | 1 | 2 | 0 | 0 | 0.43 | 0.02 | 1
5 | 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 | IFNGR1(2), JAK2(1), PTPRU(1), REG1A(1), STAT1(3) | 661911 | 8 | 7 | 8 | 1 | 4 | 3 | 0 | 0 | 1 | 0 | 0.27 | 0.021 | 1
6 | MSPPATHWAY | Macrophage stimulating protein is synthesized as pro-MSP by the liver and, on proteolysis, binds to monocyte receptor kinase RON to induce macrophage development. | CCL2, CSF1, IL1B, MST1, MST1R, TNF | 6 | MST1(1), MST1R(3) | 376583 | 4 | 4 | 4 | 0 | 2 | 2 | 0 | 0 | 0 | 0 | 0.25 | 0.03 | 1
7 | NKTPATHWAY | T cell differentiation into Th1 and Th2 cells occurs by differential chemokine receptor expression, which mediates tissue localization and immune response. | CCL3, CCL4, CCR1, CCR2, CCR3, CCR4, CCR5, CCR7, CD28, CD4, CSF2, CXCR3, CXCR4, IFNG, IFNGR1, IFNGR2, IL12A, IL12B, IL12RB1, IL12RB2, IL18R1, IL2, IL4, IL4R, IL5, TGFB1, TGFB2, TGFB3, TNFSF5 | 28 | CCL4(1), CCR7(1), IFNGR1(2), IFNGR2(2), IL12B(1), IL12RB1(1), TGFB3(2) | 1166496 | 10 | 9 | 10 | 1 | 5 | 0 | 1 | 0 | 4 | 0 | 0.2 | 0.032 | 1
8 | HSA00130_UBIQUINONE_BIOSYNTHESIS | Genes involved in ubiquinone biosynthesis | COQ2, COQ3, COQ5, COQ6, COQ7, ND1, ND2, ND3, ND4, ND4L, ND5, ND6, NDUFA12, NDUFA13, NDUFB11 | 8 | COQ3(1), COQ5(1), COQ6(1) | 232317 | 3 | 3 | 3 | 0 | 2 | 1 | 0 | 0 | 0 | 0 | 0.44 | 0.037 | 1
9 | PLK3PATHWAY | Active Plk3 phosphorylates CDC25c, blocking the G2/M transition, and phosphorylates p53 to induce apoptosis. | ATM, ATR, CDC25C, CHEK1, CHEK2, CNK, TP53, YWHAH | 7 | ATM(2), ATR(2), CHEK2(2), TP53(2) | 923540 | 8 | 8 | 7 | 0 | 4 | 0 | 0 | 3 | 1 | 0 | 0.16 | 0.038 | 1
10 | 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(1), SP3(1), TP53(2) | 407974 | 4 | 4 | 4 | 0 | 2 | 1 | 0 | 0 | 1 | 0 | 0.33 | 0.04 | 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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