Mutation Analysis (MutSig v2.0)
Cervical Squamous Cell Carcinoma (Primary solid tumor)
22 February 2013 | analyses__2013_02_22
Maintainer Information
Citation Information
doi:10.7908/C17D2S9P
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/C17D2S9P
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): 11

- Mutations seen in COSMIC: 35

- Significantly mutated genes in COSMIC territory: 1

- 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 261 blacklisted mutations: 9754

- After removing 617 noncoding mutations: 9137

Mutation Filtering

- Number of mutations before filtering: 9137

- After removing 127 mutations outside gene set: 9010

- After removing 21 mutations outside category set: 8989

Results
Breakdown of Mutations by Type

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

type | count
--- | ---
Frame_Shift_Del | 114
Frame_Shift_Ins | 65
In_Frame_Del | 52
In_Frame_Ins | 15
Missense_Mutation | 5620
Nonsense_Mutation | 474
Nonstop_Mutation | 11
Silent | 2532
Splice_Site | 93
Translation_Start_Site | 13
Total | 8989

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) | 3536 | 150569812 | 0.000023 | 23 | 4.1 | 3
(A/C/G)p*C->(T/G) | 1136 | 425623126 | 2.7e-06 | 2.7 | 0.47 | 2.7
C->A | 350 | 576192938 | 6.1e-07 | 0.61 | 0.11 | 4.4
A->mut | 611 | 556925266 | 1.1e-06 | 1.1 | 0.19 | 3.9
indel+null | 805 | 1133118204 | 7.1e-07 | 0.71 | 0.12 | NaN
double_null | 19 | 1133118204 | 1.7e-08 | 0.017 | 0.0029 | NaN
Total | 6457 | 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

CoMut Plot

Figure 3. 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: 11. 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 | PIK3CA | phosphoinositide-3-kinase, catalytic, alpha polypeptide | 126650 | 11 | 9 | 4 | 0 | 10 | 0 | 0 | 1 | 0 | 0 | 3.4e-08 | 0.12 | 0.025 | 0 | <1.00e-15 | <6.01e-12
2 | PRSS48 | protease, serine, 48 | 38982 | 16 | 2 | 9 | 3 | 0 | 3 | 2 | 9 | 2 | 0 | 0.0072 | 0.32 | 0.98 | 0 | <1.00e-15 | <6.01e-12
3 | UGT2B10 | UDP glucuronosyltransferase 2 family, polypeptide B10 | 122318 | 19 | 2 | 13 | 3 | 2 | 3 | 1 | 13 | 0 | 0 | 0.072 | 0.25 | 1 | 0 | <1.00e-15 | <6.01e-12
4 | TMCC1 | transmembrane and coiled-coil domain family 1 | 77000 | 4 | 4 | 3 | 0 | 0 | 0 | 1 | 0 | 3 | 0 | 0.00013 | 0.82 | 0.096 | 0.00014 | 3.56e-07 | 0.00161
5 | PRG4 | proteoglycan 4 | 166081 | 14 | 5 | 11 | 0 | 2 | 1 | 1 | 0 | 10 | 0 | 0.00038 | 0.46 | 0.44 | 0.00018 | 1.21e-06 | 0.00435
6 | CDC27 | cell division cycle 27 homolog (S. cerevisiae) | 97176 | 7 | 5 | 4 | 0 | 0 | 0 | 1 | 3 | 3 | 0 | 2e-05 | 0.37 | 0.05 | 0.0092 | 3.10e-06 | 0.00930
7 | NFE2L2 | nuclear factor (erythroid-derived 2)-like 2 | 69545 | 7 | 6 | 6 | 0 | 4 | 0 | 0 | 1 | 2 | 0 | 2.6e-06 | 0.34 | 0.049 | 0.18 | 7.38e-06 | 0.0190
8 | MAPK1 | mitogen-activated protein kinase 1 | 38660 | 3 | 3 | 1 | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 0.0011 | 0.41 | 0.2 | 0.00065 | 1.06e-05 | 0.0240
9 | PTH2 | parathyroid hormone 2 | 8040 | 2 | 2 | 2 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 5e-05 | 0.38 | 0.05 | 0.028 | 2.00e-05 | 0.0401
10 | UGT3A2 | UDP glycosyltransferase 3 family, polypeptide A2 | 62290 | 3 | 3 | 2 | 0 | 1 | 0 | 0 | 0 | 2 | 0 | 0.0032 | 0.69 | 0.0024 | 0.0013 | 5.57e-05 | 0.0982
11 | SSX7 | synovial sarcoma, X breakpoint 7 | 23049 | 5 | 3 | 4 | 0 | 0 | 2 | 1 | 2 | 0 | 0 | 0.000077 | 0.34 | 1 | 0.058 | 5.99e-05 | 0.0982
12 | PRB2 | proline-rich protein BstNI subfamily 2 | 49240 | 6 | 4 | 5 | 0 | 0 | 0 | 0 | 1 | 5 | 0 | 1e-05 | 0.52 | 0.34 | 0.76 | 0.000101 | 0.152
13 | RAET1L | retinoic acid early transcript 1L | 25451 | 5 | 2 | 4 | 0 | 1 | 1 | 0 | 3 | 0 | 0 | 0.005 | 0.28 | 0.53 | 0.0019 | 0.000122 | 0.170
14 | ARID1A | AT rich interactive domain 1A (SWI-like) | 226053 | 7 | 6 | 6 | 0 | 1 | 1 | 0 | 0 | 3 | 2 | 0.000025 | 0.29 | 0.53 | 1 | 0.000291 | 0.367
15 | ITGAX | integrin, alpha X (complement component 3 receptor 4 subunit) | 131027 | 8 | 4 | 6 | 6 | 2 | 2 | 0 | 3 | 1 | 0 | 0.19 | 0.96 | 0.59 | 0.00014 | 0.000313 | 0.367
16 | PLAC4 | placenta-specific 4 | 7160 | 2 | 2 | 2 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0.00014 | 1 | 0.07 | 0.2 | 0.000325 | 0.367
17 | PTEN | phosphatase and tensin homolog (mutated in multiple advanced cancers 1) | 45935 | 3 | 3 | 3 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 0.000082 | 0.59 | 0.82 | 0.39 | 0.000364 | 0.372
18 | FCRL1 | Fc receptor-like 1 | 53853 | 3 | 3 | 3 | 0 | 1 | 0 | 0 | 2 | 0 | 0 | 0.00037 | 0.45 | 0.71 | 0.088 | 0.000372 | 0.372
19 | AQP2 | aquaporin 2 (collecting duct) | 29453 | 3 | 3 | 3 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 0.000096 | 0.33 | 0.16 | 0.45 | 0.000478 | 0.454
20 | FAM49A | family with sequence similarity 49, member A | 39076 | 2 | 2 | 2 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0.0019 | 0.61 | 0.55 | 0.026 | 0.000548 | 0.494
21 | TIE1 | tyrosine kinase with immunoglobulin-like and EGF-like domains 1 | 125328 | 4 | 3 | 4 | 0 | 0 | 2 | 1 | 0 | 1 | 0 | 0.0039 | 0.29 | 0.035 | 0.016 | 0.000651 | 0.559
22 | ZNF645 | zinc finger protein 645 | 49998 | 2 | 2 | 1 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0.0044 | 0.65 | 0.07 | 0.015 | 0.000683 | 0.560
23 | USP26 | ubiquitin specific peptidase 26 | 107055 | 2 | 2 | 2 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0.026 | 0.7 | 0.0056 | 0.0026 | 0.000714 | 0.560
24 | LYZL1 | lysozyme-like 1 | 22057 | 3 | 3 | 3 | 0 | 1 | 1 | 0 | 0 | 1 | 0 | 0.00013 | 0.36 | 0.44 | 0.57 | 0.000786 | 0.580
25 | CPNE3 | copine III | 64568 | 3 | 2 | 3 | 0 | 2 | 0 | 0 | 0 | 1 | 0 | 0.041 | 0.51 | 0.98 | 0.0019 | 0.000813 | 0.580
26 | OR10G8 | olfactory receptor, family 10, subfamily G, member 8 | 36617 | 18 | 2 | 12 | 15 | 0 | 10 | 0 | 7 | 1 | 0 | 1 | 0.99 | 1 | 0.000085 | 0.000880 | 0.580
27 | ERP27 | endoplasmic reticulum protein 27 kDa | 32955 | 3 | 3 | 3 | 0 | 0 | 2 | 0 | 1 | 0 | 0 | 0.0002 | 0.46 | 0.67 | 0.44 | 0.000892 | 0.580
28 | FETUB | fetuin B | 45815 | 2 | 2 | 2 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0.01 | 0.6 | 0.029 | 0.0085 | 0.000901 | 0.580
29 | SEH1L | SEH1-like (S. cerevisiae) | 50533 | 2 | 2 | 1 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0.017 | 1 | 0.016 | 0.0056 | 0.000960 | 0.581
30 | NFYB | nuclear transcription factor Y, beta | 25367 | 2 | 2 | 1 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0.00078 | 0.55 | 0.018 | 0.12 | 0.000966 | 0.581
31 | ZNF563 | zinc finger protein 563 | 56133 | 3 | 3 | 2 | 0 | 1 | 0 | 0 | 2 | 0 | 0 | 0.0023 | 0.52 | 0.99 | 0.043 | 0.00103 | 0.596
32 | ZNF43 | zinc finger protein 43 | 95053 | 4 | 4 | 4 | 0 | 1 | 0 | 1 | 1 | 1 | 0 | 0.00017 | 0.58 | 0.74 | 0.67 | 0.00117 | 0.659
33 | OR5H6 | olfactory receptor, family 5, subfamily H, member 6 | 38003 | 3 | 3 | 3 | 0 | 1 | 0 | 0 | 1 | 1 | 0 | 0.00016 | 0.39 | 0.66 | 0.81 | 0.00133 | 0.716
34 | SSX3 | synovial sarcoma, X breakpoint 3 | 25038 | 6 | 2 | 4 | 1 | 0 | 6 | 0 | 0 | 0 | 0 | 0.0055 | 0.51 | 0.28 | 0.026 | 0.00139 | 0.716
35 | KRTAP10-1 | keratin associated protein 10-1 | 33153 | 3 | 2 | 3 | 0 | 0 | 1 | 1 | 1 | 0 | 0 | 0.0065 | 0.46 | 0.99 | 0.022 | 0.00139 | 0.716

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.

UGT2B10

Figure S3. This figure depicts the distribution of mutations and mutation types across the UGT2B10 significant gene.

TMCC1

Figure S4. This figure depicts the distribution of mutations and mutation types across the TMCC1 significant gene.

PRG4

Figure S5. This figure depicts the distribution of mutations and mutation types across the PRG4 significant gene.

CDC27

Figure S6. This figure depicts the distribution of mutations and mutation types across the CDC27 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.

SSX7

Figure S10. 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: 1. 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 | 2.2e-13 | 9.8e-10
2 | ATL2 | atlastin GTPase 2 | 1 | 1 | 1 | 39 | 1 | 0.00022 | 0.17
3 | EDA | ectodysplasin A | 1 | 1 | 1 | 39 | 1 | 0.00022 | 0.17
4 | KIAA1024 | KIAA1024 | 2 | 1 | 1 | 39 | 1 | 0.00022 | 0.17
5 | MAPK11 | mitogen-activated protein kinase 11 | 1 | 1 | 1 | 39 | 1 | 0.00022 | 0.17
6 | SUV39H2 | suppressor of variegation 3-9 homolog 2 (Drosophila) | 1 | 1 | 1 | 39 | 2 | 0.00022 | 0.17
7 | ALS2 | amyotrophic lateral sclerosis 2 (juvenile) | 2 | 3 | 1 | 117 | 1 | 0.00067 | 0.23
8 | EPHA10 | EPH receptor A10 | 1 | 3 | 1 | 117 | 1 | 0.00067 | 0.23
9 | IFITM3 | interferon induced transmembrane protein 3 (1-8U) | 5 | 3 | 1 | 117 | 1 | 0.00067 | 0.23
10 | ITIH5L | inter-alpha (globulin) inhibitor H5-like | 1 | 3 | 1 | 117 | 1 | 0.00067 | 0.23

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
--- | --- | --- | --- | --- | --- | --- | --- | --- | --- | ---
2854 | PIK3CA | phosphoinositide-3-kinase, catalytic, alpha polypeptide | 11 | 0 | 14 | 24 | 24 | 14 | 24 | 24
4403 | ZSCAN5A | zinc finger and SCAN domain containing 5A | 39 | 0 | 12 | 31 | 61 | 12 | 31 | 61
2624 | OR1S2 | olfactory receptor, family 1, subfamily S, member 2 | 33 | 0 | 11 | 27 | 39 | 11 | 27 | 39
2623 | OR1S1 | olfactory receptor, family 1, subfamily S, member 1 | 32 | 0 | 11 | 21 | 45 | 11 | 21 | 45
2196 | MAGEA12 | melanoma antigen family A, 12 | 29 | 0 | 10 | 26 | 44 | 10 | 26 | 44
3034 | PRSS48 | protease, serine, 48 | 16 | 0 | 6 | 22 | 54 | 6 | 22 | 54
2613 | OR10G8 | olfactory receptor, family 10, subfamily G, member 8 | 18 | 0 | 5 | 5 | 13 | 5 | 5 | 13
1773 | IFITM2 | interferon induced transmembrane protein 2 (1-8D) | 9 | 0 | 3 | 3 | 5 | 3 | 3 | 5
2231 | MAPK1 | mitogen-activated protein kinase 1 | 3 | 0 | 3 | 3 | 3 | 3 | 3 | 3
4404 | 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 | 0.00048 | 0.14
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 | 0.0005 | 0.14
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 | 0.00078 | 0.14
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 | 0.0009 | 0.14
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 | 0.0016 | 0.17
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 | 0.0017 | 0.17
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 | 0.0019 | 0.17
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 | 0.0022 | 0.17
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 | 0.0032 | 0.2
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 | 0.0032 | 0.2

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 | 0.0019 | 0.69
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 | 0.0022 | 0.69
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 | 0.019 | 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 | 0.02 | 1
6 | 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 | 0.029 | 1
7 | 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 | 0.036 | 1
8 | 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 | 18 | ADCY1(1), ARHGEF1(1), F2R(1), F2RL3(2), GNA13(1), PIK3R1(1), PPP1R12B(1), PRKCA(1), ROCK1(3) | 1351925 | 12 | 9 | 12 | 1 | 6 | 3 | 1 | 1 | 0 | 1 | 0.13 | 0.038 | 1
9 | 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 | 0.039 | 1
10 | ERBB4PATHWAY | ErbB4 (aka HER4) is a receptor tyrosine kinase that binds neuregulins as well as members of the EGF family, which also target EGF receptors. | ADAM17, ERBB4, NRG2, NRG3, PRKCA, PRKCB1, PSEN1 | 6 | ADAM17(2), ERBB4(1), PRKCA(1), PSEN1(2) | 515411 | 6 | 5 | 6 | 1 | 4 | 1 | 0 | 1 | 0 | 0 | 0.47 | 0.052 | 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.

- 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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