Bladder Urothelial Carcinoma: Mutation Analysis (MutSig)
Maintained by Dan DiCara (Broad Institute)
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.

Number of patients in set: 28

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.final_analysis_set.maf

Significantly mutated genes (q ≤ 0.1): 7

Mutations seen in COSMIC: 37

Significantly mutated genes in COSMIC territory: 3

Genes with clustered mutations (≤ 3 aa apart): 0

Significantly mutated genesets: 33

Significantly mutated genesets: (excluding sig. mutated genes): 7

Mutation Preprocessing

Read 28 MAFs of type "Broad"

Total number of mutations in input MAFs: 10380

After removing 4 mutations outside chr1-24: 10376

After removing 2976 noncoding mutations: 7400

After collapsing adjacent/redundant mutations: 7359

Mutation Filtering

Number of mutations before filtering: 7359

After removing 114 mutations outside gene set: 7245

After removing 12 mutations outside category set: 7233

Results
Breakdown of Mutations by Type

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

type | count
--- | ---
Frame_Shift_Del | 98
Frame_Shift_Ins | 45
In_Frame_Del | 29
In_Frame_Ins | 5
Missense_Mutation | 4694
Nonsense_Mutation | 413
Nonstop_Mutation | 9
Silent | 1816
Splice_Site | 116
Translation_Start_Site | 8
Total | 7233

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) | 2640 | 110997796 | 0.000024 | 24 | 3.7 | 3
Tp*C->A | 201 | 110997796 | 1.8e-06 | 1.8 | 0.28 | 4
(A/C/G)p*C->mut | 1237 | 315457576 | 3.9e-06 | 3.9 | 0.61 | 3.2
A->mut | 620 | 410210248 | 1.5e-06 | 1.5 | 0.23 | 3.9
indel+null | 707 | 836665620 | 8.5e-07 | 0.85 | 0.13 | NaN
double_null | 12 | 836665620 | 1.4e-08 | 0.014 | 0.0022 | NaN
Total | 5417 | 836665620 | 6.5e-06 | 6.5 | 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).

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.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

Table 3. Get Full Table A Ranked List of Significantly Mutated Genes. Number of significant genes found: 7. 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_ks | p_cons | p_joint | p | q
--- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | ---
1 | TP53 | tumor protein p53 | 35224 | 14 | 11 | 13 | 0 | 2 | 0 | 8 | 1 | 3 | 0 | <1.00e-15 | 0.025 | 0.000019 | 0.0025 | 0.000015 | <0.00 | <0.00
2 | FBXW7 | F-box and WD repeat domain containing 7 | 72184 | 6 | 5 | 5 | 0 | 2 | 0 | 2 | 0 | 2 | 0 | 1.31e-06 | 0.34 | 0.0027 | 0.055 | 0.0028 | 7.48e-08 | 0.00068
3 | ZNF814 | zinc finger protein 814 | 54600 | 3 | 3 | 1 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 0.0012 | 0.59 | 4.2e-06 | 0.99 | 6.4e-06 | 1.53e-07 | 0.00092
4 | KDM6A |  | 116116 | 6 | 6 | 6 | 2 | 0 | 0 | 0 | 0 | 6 | 0 | 4.20e-08 | 0.98 | 0.85 | 0.39 | 0.87 | 6.62e-07 | 0.0030
5 | NFE2L2 | nuclear factor (erythroid-derived 2)-like 2 | 50092 | 4 | 4 | 4 | 0 | 1 | 0 | 1 | 2 | 0 | 0 | 0.000016 | 0.4 | 0.27 | 0.0077 | 0.026 | 6.56e-06 | 0.021
6 | ARID1A | AT rich interactive domain 1A (SWI-like) | 162316 | 8 | 6 | 8 | 1 | 3 | 0 | 0 | 0 | 5 | 0 | 7.47e-07 | 0.66 | 0.31 | 0.94 | 0.6 | 6.97e-06 | 0.021
7 | LLGL2 | lethal giant larvae homolog 2 (Drosophila) | 79548 | 2 | 2 | 1 | 1 | 0 | 0 | 0 | 0 | 2 | 0 | 0.0094 | 1 | 0.00033 | 0.97 | 0.00033 | 0.000043 | 0.11
8 | TMCO2 | transmembrane and coiled-coil domains 2 | 15596 | 2 | 2 | 1 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0.00028 | 1 | 0.0018 | 0.87 | 0.016 | 0.000061 | 0.13
9 | POTEC |  | 43120 | 3 | 3 | 2 | 0 | 0 | 0 | 2 | 1 | 0 | 0 | 0.00012 | 0.55 | 0.0089 | 0.86 | 0.042 | 0.000066 | 0.13
10 | HCN1 | hyperpolarization activated cyclic nucleotide-gated potassium channel 1 | 69300 | 4 | 4 | 4 | 1 | 1 | 0 | 1 | 0 | 1 | 1 | 6.48e-06 | 0.61 | 0.31 | 0.73 | 0.88 | 0.000075 | 0.13
11 | CREBBP | CREB binding protein (Rubinstein-Taybi syndrome) | 200396 | 5 | 5 | 5 | 1 | 0 | 0 | 2 | 0 | 3 | 0 | 0.00010 | 0.54 | 0.051 | 0.25 | 0.059 | 0.000081 | 0.13
12 | CUL1 | cullin 1 | 67620 | 4 | 4 | 3 | 0 | 3 | 0 | 1 | 0 | 0 | 0 | 0.00036 | 0.37 | 0.57 | 0.006 | 0.019 | 0.000090 | 0.14
13 | PYGO1 | pygopus homolog 1 (Drosophila) | 35616 | 3 | 3 | 3 | 0 | 0 | 0 | 1 | 1 | 1 | 0 | 0.000062 | 0.52 | 0.089 | 0.62 | 0.15 | 0.00012 | 0.16
14 | GPS2 | G protein pathway suppressor 2 | 28448 | 3 | 3 | 3 | 0 | 0 | 1 | 0 | 0 | 1 | 1 | 0.000016 | 0.57 | 0.39 | 0.41 | 0.63 | 0.00013 | 0.16
15 | MLL | myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila) | 327628 | 9 | 7 | 8 | 1 | 7 | 0 | 0 | 0 | 2 | 0 | 0.0016 | 0.48 | 0.003 | 0.61 | 0.0082 | 0.00016 | 0.19
16 | HLA-A | major histocompatibility complex, class I, A | 31220 | 3 | 3 | 3 | 0 | 0 | 0 | 1 | 0 | 2 | 0 | 0.000014 | 0.54 | 1 | 0.65 | 1 | 0.00017 | 0.19
17 | RAP1B | RAP1B, member of RAS oncogene family | 16212 | 2 | 2 | 2 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0.0029 | 0.66 | 0.35 | 0.0093 | 0.0059 | 0.00021 | 0.22
18 | ERCC2 | excision repair cross-complementing rodent repair deficiency, complementation group 2 (xeroderma pigmentosum D) | 60592 | 4 | 4 | 4 | 0 | 1 | 0 | 1 | 2 | 0 | 0 | 0.000076 | 0.36 | 0.9 | 0.021 | 0.24 | 0.00021 | 0.22
19 | HCRT | hypocretin (orexin) neuropeptide precursor | 3668 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0.00029 | 1 | NaN | NaN | NaN | 0.00029 | 0.27
20 | ELF3 | E74-like factor 3 (ets domain transcription factor, epithelial-specific ) | 32144 | 3 | 3 | 3 | 0 | 0 | 0 | 1 | 0 | 2 | 0 | 0.000026 | 0.72 | 0.44 | 0.47 | 1 | 0.00030 | 0.27
21 | C17orf81 | chromosome 17 open reading frame 81 | 30464 | 3 | 2 | 3 | 1 | 2 | 0 | 1 | 0 | 0 | 0 | 0.0040 | 0.78 | 0.0076 | 0.08 | 0.0071 | 0.00032 | 0.28
22 | HMCN1 | hemicentin 1 | 485408 | 9 | 8 | 9 | 0 | 4 | 0 | 1 | 2 | 2 | 0 | 0.00048 | 0.14 | 0.27 | 0.034 | 0.065 | 0.00036 | 0.29
23 | AHCTF1 | AT hook containing transcription factor 1 | 194544 | 2 | 2 | 2 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0.24 | 0.73 | 0.00014 | 0.75 | 0.00014 | 0.00037 | 0.29
24 | XPR1 | xenotropic and polytropic retrovirus receptor | 60228 | 5 | 4 | 5 | 1 | 3 | 0 | 0 | 0 | 2 | 0 | 0.000082 | 0.64 | 0.28 | 0.43 | 0.47 | 0.00043 | 0.33
25 | RFTN2 | raftlin family member 2 | 40152 | 3 | 3 | 3 | 0 | 1 | 0 | 0 | 0 | 2 | 0 | 0.00012 | 0.6 | 0.32 | 0.49 | 0.35 | 0.00046 | 0.33
26 | NAA25 |  | 82684 | 4 | 4 | 4 | 0 | 1 | 1 | 1 | 0 | 1 | 0 | 0.00031 | 0.44 | 0.12 | 0.84 | 0.15 | 0.00052 | 0.36
27 | BCLAF1 | BCL2-associated transcription factor 1 | 78596 | 5 | 4 | 5 | 0 | 2 | 0 | 0 | 2 | 1 | 0 | 0.00013 | 0.4 | 0.24 | 0.86 | 0.39 | 0.00053 | 0.36
28 | C9orf41 | chromosome 9 open reading frame 41 | 28980 | 2 | 1 | 2 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0.046 | 0.68 | 0.0011 | 0.78 | 0.0011 | 0.00055 | 0.36
29 | KRTAP4-9 | keratin associated protein 4-9 | 12656 | 2 | 2 | 2 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 0.00017 | 0.9 | 0.44 | 0.44 | 0.54 | 0.00092 | 0.56
30 | SPG11 | spastic paraplegia 11 (autosomal recessive) | 206248 | 2 | 1 | 2 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0.39 | 0.63 | 0.00029 | 0.53 | 0.00023 | 0.00093 | 0.56
31 | PCDHAC1 | protocadherin alpha subfamily C, 1 | 82096 | 4 | 4 | 4 | 0 | 1 | 0 | 1 | 2 | 0 | 0 | 0.000097 | 0.33 | 0.77 | 0.81 | 1 | 0.00099 | 0.58
32 | LETMD1 | LETM1 domain containing 1 | 31332 | 3 | 3 | 3 | 0 | 1 | 0 | 0 | 2 | 0 | 0 | 0.00047 | 0.42 | 0.83 | 0.097 | 0.24 | 0.0011 | 0.63
33 | FEZ2 | fasciculation and elongation protein zeta 2 (zygin II) | 22624 | 2 | 2 | 2 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0.0014 | 0.77 | 0.059 | 0.57 | 0.087 | 0.0012 | 0.63
34 | CREB3L3 | cAMP responsive element binding protein 3-like 3 | 39256 | 3 | 2 | 3 | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 0.014 | 0.37 | 0.047 | 0.0094 | 0.0089 | 0.0013 | 0.63
35 | OPCML | opioid binding protein/cell adhesion molecule-like | 31668 | 3 | 3 | 3 | 0 | 1 | 0 | 1 | 1 | 0 | 0 | 0.00013 | 0.4 | 0.89 | 0.94 | 1 | 0.0013 | 0.63

TP53

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

FBXW7

Figure S2. This figure depicts the distribution of mutations and mutation types across the FBXW7 significant gene.

ZNF814

Figure S3. This figure depicts the distribution of mutations and mutation types across the ZNF814 significant gene.

KDM6A

Figure S4. This figure depicts the distribution of mutations and mutation types across the KDM6A significant gene.

NFE2L2

Figure S5. This figure depicts the distribution of mutations and mutation types across the NFE2L2 significant gene.

Note:

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 .

null - mutation category that includes nonsense, frameshift, splice-site mutations

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 = p-value (overall)

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

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: 3. Number of genes displayed: 10

rank | gene | description | n | cos | n_cos | N_cos | cos_ev | p | q
--- | --- | --- | --- | --- | --- | --- | --- | --- | ---
1 | TP53 | tumor protein p53 | 14 | 308 | 14 | 8624 | 3048 | 0 | 0
2 | FBXW7 | F-box and WD repeat domain containing 7 | 6 | 91 | 4 | 2548 | 102 | 3e-09 | 6.9e-06
3 | FGFR3 | fibroblast growth factor receptor 3 (achondroplasia, thanatophoric dwarfism) | 2 | 43 | 2 | 1204 | 216 | 3e-05 | 0.046
4 | DPYSL4 | dihydropyrimidinase-like 4 | 1 | 1 | 1 | 28 | 2 | 0.00018 | 0.16
5 | TBC1D8B | TBC1 domain family, member 8B (with GRAM domain) | 2 | 1 | 1 | 28 | 1 | 0.00018 | 0.16
6 | BMX | BMX non-receptor tyrosine kinase | 2 | 2 | 1 | 56 | 2 | 0.00036 | 0.23
7 | GABRA6 | gamma-aminobutyric acid (GABA) A receptor, alpha 6 | 2 | 2 | 1 | 56 | 1 | 0.00036 | 0.23
8 | IDH1 | isocitrate dehydrogenase 1 (NADP+), soluble | 1 | 3 | 1 | 84 | 1492 | 0.00054 | 0.27
9 | PIK3CA | phosphoinositide-3-kinase, catalytic, alpha polypeptide | 3 | 184 | 2 | 5152 | 375 | 0.00054 | 0.27
10 | BAZ1A | bromodomain adjacent to zinc finger domain, 1A | 1 | 4 | 1 | 112 | 1 | 0.00072 | 0.27

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

There were no clustered mutations discovered.

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: 33. 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(5), DAXX(1), PML(3), RARA(2), RB1(2), SP100(1), TNFRSF1B(1), TP53(14) | 809704 | 29 | 17 | 27 | 1 | 7 | 0 | 13 | 1 | 7 | 1 | 0.003 | 4.5e-13 | 2.8e-10
2 | 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 | SP3(2), TP53(14) | 296856 | 16 | 12 | 15 | 1 | 4 | 0 | 8 | 1 | 3 | 0 | 0.076 | 4.1e-11 | 1.3e-08
3 | 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(3), RB1(2), TP53(14), WEE1(1) | 742224 | 20 | 16 | 18 | 2 | 3 | 0 | 9 | 2 | 5 | 1 | 0.16 | 1.5e-10 | 3.1e-08
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 | IFNGR2(1), JAK2(1), RB1(2), RELA(1), TNFRSF1B(1), TP53(14), USH1C(1) | 774256 | 21 | 15 | 19 | 0 | 5 | 1 | 9 | 1 | 4 | 1 | 0.0039 | 2.3e-10 | 3.5e-08
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 | DNAJC3(1), RELA(1), TP53(14) | 412412 | 16 | 12 | 15 | 0 | 4 | 0 | 8 | 1 | 3 | 0 | 0.019 | 4.8e-09 | 6e-07
6 | 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 | CCND1(1), CDKN1A(2), E2F2(1), TP53(14) | 361788 | 18 | 12 | 17 | 2 | 4 | 0 | 9 | 2 | 3 | 0 | 0.11 | 1.5e-08 | 1.5e-06
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 | ATM(3), BAX(1), CCND1(1), CDKN1A(2), RB1(2), TP53(14) | 766220 | 23 | 16 | 21 | 3 | 5 | 0 | 10 | 2 | 5 | 1 | 0.17 | 3.3e-08 | 2.9e-06
8 | 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(3), ATR(3), TP53(14) | 674632 | 20 | 13 | 19 | 1 | 6 | 0 | 9 | 2 | 3 | 0 | 0.069 | 4.2e-08 | 3.2e-06
9 | G1PATHWAY | CDK4/6-cyclin D and CDK2-cyclin E phosphorylate Rb, which allows the transcription of genes needed for the G1/S cell cycle transition. | ABL1, ATM, ATR, CCNA1, CCND1, CCNE1, CDC2, CDC25A, CDK2, CDK4, CDK6, CDKN1A, CDKN1B, CDKN2A, CDKN2B, DHFR, E2F1, GSK3B, HDAC1, MADH3, MADH4, RB1, SKP2, TFDP1, TGFB1, TGFB2, TGFB3, TP53 | 25 | ABL1(1), ATM(3), ATR(3), CCND1(1), CDK6(1), CDKN1A(2), RB1(2), TP53(14) | 1280076 | 27 | 17 | 25 | 2 | 10 | 0 | 10 | 2 | 4 | 1 | 0.031 | 2e-07 | 0.000013
10 | 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 | CUL1(4), FBXW7(6), RB1(2) | 353976 | 12 | 9 | 9 | 0 | 5 | 0 | 3 | 0 | 3 | 1 | 0.06 | 6.5e-07 | 4e-05

Table 6. Get Full Table A Ranked List of Significantly Mutated Genesets (Excluding Significantly Mutated Genes). Number of significant genesets found: 7. 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 | 12 | CREBBP(5), DAXX(1), PML(3), RARA(2), RB1(2), SP100(1), TNFRSF1B(1) | 774480 | 15 | 11 | 14 | 1 | 5 | 0 | 5 | 0 | 4 | 1 | 0.074 | 0.000022 | 0.0076
2 | CTLPATHWAY | Cytotoxic T lymphocytes induce apoptosis in infected cells presenting antigen-MHC-I complexes via the perforin and Fas/Fas ligand pathways. | B2M, CD3D, CD3E, CD3G, CD3Z, GZMB, HLA-A, ICAM1, ITGAL, ITGB2, PRF1, TNFRSF6, TNFSF6, TRA@, TRB@ | 10 | B2M(1), GZMB(1), HLA-A(3), ICAM1(1), PRF1(3) | 367304 | 9 | 8 | 9 | 1 | 2 | 0 | 4 | 1 | 2 | 0 | 0.25 | 0.000025 | 0.0076
3 | 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 | 7 | CUL1(4), RB1(2) | 281792 | 6 | 6 | 4 | 0 | 3 | 0 | 1 | 0 | 1 | 1 | 0.2 | 0.00022 | 0.043
4 | D4GDIPATHWAY | D4-GDI inhibits the pro-apoptotic Rho GTPases and is cleaved by caspase-3. | ADPRT, APAF1, ARHGAP5, ARHGDIB, CASP1, CASP10, CASP3, CASP8, CASP9, CYCS, GZMB, JUN, PRF1 | 12 | ARHGAP5(4), CASP8(2), GZMB(1), PRF1(3) | 540764 | 10 | 9 | 10 | 1 | 1 | 0 | 5 | 4 | 0 | 0 | 0.28 | 0.00028 | 0.043
5 | IL7PATHWAY | IL-7 is required for B and T cell development and proliferation and may contribute to activation of VDJ recombination. | BCL2, CREBBP, EP300, FYN, IL2RG, IL7, IL7R, JAK1, JAK3, LCK, NMI, PIK3CA, PIK3R1, PTK2B, STAT5A, STAT5B | 16 | CREBBP(5), EP300(3), IL2RG(1), JAK1(1), LCK(1), PIK3CA(3), PIK3R1(1), STAT5B(1) | 1181796 | 16 | 14 | 16 | 2 | 5 | 1 | 5 | 2 | 3 | 0 | 0.17 | 0.0004 | 0.049
6 | P27PATHWAY | p27 blocks the G1/S transition by inhibiting the checkpoint kinase cdk2/cyclin E and is inhibited by cdk2-mediated ubiquitination. | CCNE1, CDK2, CDKN1B, CKS1B, CUL1, E2F1, NEDD8, RB1, RBX1, SKP1A, SKP2, TFDP1, UBE2M | 12 | CUL1(4), RB1(2) | 364224 | 6 | 6 | 4 | 0 | 3 | 0 | 1 | 0 | 1 | 1 | 0.2 | 0.00082 | 0.073
7 | SKP2E2FPATHWAY | E2F-1, a transcription factor that promotes the G1/S transition, is repressed by Rb and activated by cdk2/cyclin E. | CCNA1, CCNE1, CDC34, CDK2, CUL1, E2F1, RB1, SKP1A, SKP2, TFDP1 | 9 | CUL1(4), RB1(2) | 363692 | 6 | 6 | 4 | 1 | 3 | 0 | 1 | 0 | 1 | 1 | 0.47 | 0.00083 | 0.073
8 | PDGFPATHWAY | Platelet-derived growth factor (PDGF) receptor is phosphorylated on ligand binding and promotes cell proliferation. | CSNK2A1, ELK1, FOS, GRB2, HRAS, JAK1, JUN, MAP2K1, MAP2K4, MAP3K1, MAPK3, MAPK8, PDGFA, PDGFRA, PIK3CA, PIK3R1, PLCG1, PRKCA, PRKCB1, RAF1, RASA1, SHC1, SOS1, SRF, STAT1, STAT3, STAT5A | 26 | CSNK2A1(1), FOS(1), JAK1(1), MAP2K1(1), MAP3K1(2), MAPK8(2), PDGFRA(1), PIK3CA(3), PIK3R1(1), PLCG1(2), RASA1(1), SOS1(2), STAT1(1) | 1463532 | 19 | 14 | 19 | 1 | 11 | 1 | 4 | 2 | 1 | 0 | 0.036 | 0.0017 | 0.13
9 | N_GLYCAN_DEGRADATION |  | AGA, FLJ21865, FUCA1, FUCA2, GLB1, HEXA, HEXB, LCT, MAN2C1, MANBA, NEU1, NEU2, NEU3, NEU4 | 13 | FUCA2(1), GLB1(1), HEXA(1), LCT(4), MANBA(1), NEU2(2) | 701792 | 10 | 9 | 10 | 0 | 5 | 1 | 1 | 1 | 2 | 0 | 0.076 | 0.0022 | 0.14
10 | RAC1PATHWAY | Rac-1 is a Rho family G protein that stimulates formation of actin-dependent structures such as filopodia and lamellopodia. | ARFIP2, CDK5, CDK5R1, CFL1, CHN1, LIMK1, MAP3K1, MYL2, MYLK, NCF2, PAK1, PDGFRA, PIK3CA, PIK3R1, PLD1, PPP1R12B, RAC1, RALBP1, RPS6KB1, TRIO, VAV1, WASF1 | 22 | CDK5(1), CHN1(1), MAP3K1(2), MYLK(2), NCF2(2), PDGFRA(1), PIK3CA(3), PIK3R1(1), PPP1R12B(1), TRIO(4) | 1471820 | 18 | 14 | 18 | 0 | 8 | 2 | 5 | 1 | 2 | 0 | 0.0088 | 0.0024 | 0.14

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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