Bladder Urothelial Carcinoma: Mutation Analysis (MutSig v2.0)
(primary solid tumor cohort)
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-TP

- 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-TP.final_analysis_set.maf

- Significantly mutated genes (q ≤ 0.1): 6

- Mutations seen in COSMIC: 37

- Significantly mutated genes in COSMIC territory: 3

- Genes with clustered mutations (≤ 3 aa apart): 34

- Significantly mutated genesets: 25

- Significantly mutated genesets: (excluding sig. mutated genes):4

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 553 blacklisted mutations: 9823

- After removing 2497 noncoding mutations: 7326

- After collapsing adjacent/redundant mutations: 7285

Mutation Filtering

- Number of mutations before filtering: 7285

- After removing 88 mutations outside gene set: 7197

- After removing 11 mutations outside category set: 7186

Results
Breakdown of Mutations by Type

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

type | count
--- | ---
Frame_Shift_Del | 93
Frame_Shift_Ins | 39
In_Frame_Del | 23
In_Frame_Ins | 4
Missense_Mutation | 4673
Nonsense_Mutation | 413
Nonstop_Mutation | 9
Silent | 1810
Splice_Site | 114
Translation_Start_Site | 8
Total | 7186

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) | 2638 | 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 | 1223 | 315457576 | 3.9e-06 | 3.9 | 0.6 | 3.2
A->mut | 615 | 410210248 | 1.5e-06 | 1.5 | 0.23 | 3.9
indel+null | 688 | 836665620 | 8.2e-07 | 0.82 | 0.13 | NaN
double_null | 11 | 836665620 | 1.3e-08 | 0.013 | 0.002 | NaN
Total | 5376 | 836665620 | 6.4e-06 | 6.4 | 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-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: Tp*C->A

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

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

- n5 = number of nonsilent mutations of type: indel+null

- n6 = number of nonsilent mutations of type: double_null

- p_classic = p-value for the observed amount of nonsilent mutations being elevated in this gene

- p_ns_s = p-value for the observed nonsilent/silent ratio being elevated in this gene

- p_cons = p-value for enrichment of mutations at evolutionarily most-conserved sites in gene

- p_joint = p-value for clustering + conservation

- p = p-value (overall)

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

Table 3. Get Full Table A Ranked List of Significantly Mutated Genes. Number of significant genes found: 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_cons | p_joint | p | q
--- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | ---
1 | TP53 | tumor protein p53 | 35224 | 14 | 11 | 13 | 0 | 2 | 0 | 8 | 1 | 3 | 0 | 5.9e-15 | 0.025 | NaN | NaN | 5.9e-15 | 1.1e-10
2 | KDM6A | lysine (K)-specific demethylase 6A | 116116 | 6 | 6 | 6 | 2 | 0 | 0 | 0 | 0 | 6 | 0 | 4.4e-06 | 0.98 | NaN | NaN | 4.4e-06 | 0.04
3 | FBXW7 | F-box and WD repeat domain containing 7 | 72184 | 6 | 5 | 5 | 0 | 2 | 0 | 2 | 0 | 2 | 0 | 9.4e-06 | 0.34 | NaN | NaN | 9.4e-06 | 0.057
4 | GPS2 | G protein pathway suppressor 2 | 28448 | 3 | 3 | 3 | 0 | 0 | 1 | 0 | 0 | 1 | 1 | 0.000015 | 0.57 | NaN | NaN | 0.000015 | 0.058
5 | NFE2L2 | nuclear factor (erythroid-derived 2)-like 2 | 50092 | 4 | 4 | 4 | 0 | 1 | 0 | 1 | 2 | 0 | 0 | 0.000016 | 0.4 | NaN | NaN | 0.000016 | 0.058
6 | HCN1 | hyperpolarization activated cyclic nucleotide-gated potassium channel 1 | 69300 | 4 | 4 | 4 | 1 | 1 | 0 | 1 | 0 | 1 | 1 | 0.000022 | 0.61 | NaN | NaN | 0.000022 | 0.065
7 | ARID1A | AT rich interactive domain 1A (SWI-like) | 162316 | 8 | 6 | 8 | 1 | 3 | 0 | 0 | 0 | 5 | 0 | 0.000051 | 0.66 | NaN | NaN | 0.000051 | 0.13
8 | PPBP | pro-platelet basic protein (chemokine (C-X-C motif) ligand 7) | 11172 | 2 | 2 | 2 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0.00011 | 0.56 | NaN | NaN | 0.00011 | 0.2
9 | HLA-A | major histocompatibility complex, class I, A | 31220 | 3 | 3 | 3 | 0 | 0 | 0 | 1 | 0 | 2 | 0 | 0.00012 | 0.54 | NaN | NaN | 0.00012 | 0.2
10 | 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 | 0.00012 | 0.36 | NaN | NaN | 0.00012 | 0.2
11 | PCDHAC1 | protocadherin alpha subfamily C, 1 | 82096 | 4 | 4 | 4 | 0 | 1 | 0 | 1 | 2 | 0 | 0 | 0.00012 | 0.33 | NaN | NaN | 0.00012 | 0.2
12 | ELF3 | E74-like factor 3 (ets domain transcription factor, epithelial-specific ) | 32144 | 3 | 3 | 3 | 0 | 0 | 0 | 1 | 0 | 2 | 0 | 0.00019 | 0.72 | NaN | NaN | 0.00019 | 0.22
13 | HRNR | hornerin | 183680 | 6 | 6 | 6 | 0 | 2 | 1 | 2 | 1 | 0 | 0 | 0.00019 | 0.34 | NaN | NaN | 0.00019 | 0.22
14 | BCLAF1 | BCL2-associated transcription factor 1 | 78596 | 5 | 4 | 5 | 0 | 2 | 0 | 0 | 2 | 1 | 0 | 0.00019 | 0.4 | NaN | NaN | 0.00019 | 0.22
15 | PYGO1 | pygopus homolog 1 (Drosophila) | 35616 | 3 | 3 | 3 | 0 | 0 | 0 | 1 | 1 | 1 | 0 | 0.00019 | 0.52 | NaN | NaN | 0.00019 | 0.22
16 | OTUD7A | OTU domain containing 7A | 54404 | 4 | 4 | 4 | 0 | 3 | 0 | 1 | 0 | 0 | 0 | 0.0002 | 0.28 | NaN | NaN | 0.0002 | 0.22
17 | OPCML | opioid binding protein/cell adhesion molecule-like | 31668 | 3 | 3 | 3 | 0 | 1 | 0 | 1 | 1 | 0 | 0 | 0.00022 | 0.4 | NaN | NaN | 0.00022 | 0.23
18 | XPR1 | xenotropic and polytropic retrovirus receptor | 60228 | 5 | 4 | 5 | 1 | 3 | 0 | 0 | 0 | 2 | 0 | 0.00029 | 0.64 | NaN | NaN | 0.00029 | 0.29
19 | NAA25 | N(alpha)-acetyltransferase 25, NatB auxiliary subunit | 82684 | 4 | 4 | 4 | 0 | 1 | 1 | 1 | 0 | 1 | 0 | 0.00031 | 0.44 | NaN | NaN | 0.00031 | 0.3
20 | CUL1 | cullin 1 | 67620 | 4 | 4 | 3 | 0 | 3 | 0 | 1 | 0 | 0 | 0 | 0.00041 | 0.37 | NaN | NaN | 0.00041 | 0.37
21 | KRTAP4-9 | keratin associated protein 4-9 | 12656 | 2 | 2 | 2 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 0.00043 | 0.9 | NaN | NaN | 0.00043 | 0.37
22 | C11orf85 | chromosome 11 open reading frame 85 | 19124 | 2 | 2 | 2 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0.00047 | 0.58 | NaN | NaN | 0.00047 | 0.39
23 | RFTN2 | raftlin family member 2 | 40152 | 3 | 3 | 3 | 0 | 1 | 0 | 0 | 0 | 2 | 0 | 0.00052 | 0.6 | NaN | NaN | 0.00052 | 0.41
24 | LETMD1 | LETM1 domain containing 1 | 31332 | 3 | 3 | 3 | 0 | 1 | 0 | 0 | 2 | 0 | 0 | 0.00057 | 0.42 | NaN | NaN | 0.00057 | 0.43
25 | MTERFD2 | MTERF domain containing 2 | 31836 | 3 | 3 | 3 | 0 | 1 | 0 | 1 | 1 | 0 | 0 | 0.00068 | 0.48 | NaN | NaN | 0.00068 | 0.49
26 | IL34 | interleukin 34 | 20188 | 2 | 2 | 2 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0.00073 | 0.46 | NaN | NaN | 0.00073 | 0.49
27 | HEG1 | HEG homolog 1 (zebrafish) | 99540 | 4 | 4 | 4 | 0 | 1 | 0 | 0 | 2 | 1 | 0 | 0.00073 | 0.36 | NaN | NaN | 0.00073 | 0.49
28 | ZNF99 | zinc finger protein 99 | 87948 | 3 | 3 | 3 | 0 | 0 | 1 | 0 | 2 | 0 | 0 | 0.00086 | 0.6 | NaN | NaN | 0.00086 | 0.56
29 | C7orf36 | chromosome 7 open reading frame 36 | 19404 | 2 | 2 | 2 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0.00096 | 0.65 | NaN | NaN | 0.00096 | 0.59
30 | SLMAP | sarcolemma associated protein | 70560 | 3 | 3 | 3 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 0.001 | 0.67 | NaN | NaN | 0.001 | 0.59
31 | PRF1 | perforin 1 (pore forming protein) | 45332 | 3 | 3 | 3 | 0 | 0 | 0 | 2 | 1 | 0 | 0 | 0.001 | 0.42 | NaN | NaN | 0.001 | 0.59
32 | CDH22 | cadherin-like 22 | 52976 | 3 | 3 | 3 | 0 | 1 | 0 | 1 | 1 | 0 | 0 | 0.001 | 0.43 | NaN | NaN | 0.001 | 0.59
33 | ACN9 | ACN9 homolog (S. cerevisiae) | 10808 | 2 | 2 | 2 | 1 | 1 | 0 | 0 | 1 | 0 | 0 | 0.0012 | 0.89 | NaN | NaN | 0.0012 | 0.68
34 | OR5K2 | olfactory receptor, family 5, subfamily K, member 2 | 26712 | 2 | 2 | 2 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0.0013 | 0.61 | NaN | NaN | 0.0013 | 0.69
35 | CREBBP | CREB binding protein (Rubinstein-Taybi syndrome) | 200396 | 5 | 5 | 5 | 1 | 0 | 0 | 2 | 0 | 3 | 0 | 0.0014 | 0.54 | NaN | NaN | 0.0014 | 0.71

TP53

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

KDM6A

Figure S2. This figure depicts the distribution of mutations and mutation types across the KDM6A significant gene.

FBXW7

Figure S3. This figure depicts the distribution of mutations and mutation types across the FBXW7 significant gene.

GPS2

Figure S4. This figure depicts the distribution of mutations and mutation types across the GPS2 significant gene.

NFE2L2

Figure S5. This figure depicts the distribution of mutations and mutation types across the NFE2L2 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: 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 | 356 | 14 | 9968 | 3048 | 0 | 0
2 | FBXW7 | F-box and WD repeat domain containing 7 | 6 | 91 | 4 | 2548 | 102 | 2.9e-09 | 6.7e-06
3 | FGFR3 | fibroblast growth factor receptor 3 (achondroplasia, thanatophoric dwarfism) | 2 | 62 | 2 | 1736 | 216 | 0.000062 | 0.093
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 | BAZ1A | bromodomain adjacent to zinc finger domain, 1A | 1 | 4 | 1 | 112 | 1 | 0.00072 | 0.31
9 | PHIP | pleckstrin homology domain interacting protein | 3 | 4 | 1 | 112 | 1 | 0.00072 | 0.31
10 | SCN9A | sodium channel, voltage-gated, type IX, alpha subunit | 1 | 4 | 1 | 112 | 1 | 0.00072 | 0.31

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
--- | --- | --- | --- | --- | --- | --- | --- | --- | --- | ---
881 | CUL1 | cullin 1 | 4 | 0 | 1 | 1 | 1 | 1 | 1 | 1
1277 | FBXW7 | F-box and WD repeat domain containing 7 | 6 | 0 | 1 | 1 | 1 | 1 | 1 | 1
2150 | MLL | myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila) | 9 | 0 | 1 | 1 | 1 | 1 | 1 | 1
2908 | RB1 | retinoblastoma 1 (including osteosarcoma) | 2 | 0 | 1 | 1 | 1 | 1 | 1 | 1
3222 | SLC39A3 | solute carrier family 39 (zinc transporter), member 3 | 2 | 0 | 1 | 1 | 1 | 1 | 1 | 1
3574 | TP53 | tumor protein p53 | 13 | 1 | 0 | 4 | 13 | 0 | 4 | 13
3022 | RPL31 | ribosomal protein L31 | 3 | 1 | 0 | 3 | 3 | 0 | 3 | 3
2652 | PIK3CB | phosphoinositide-3-kinase, catalytic, beta polypeptide | 4 | 1 | 0 | 1 | 3 | 0 | 1 | 3
524 | C9orf41 | chromosome 9 open reading frame 41 | 2 | 1 | 0 | 1 | 1 | 0 | 1 | 1
880 | CUBN | cubilin (intrinsic factor-cobalamin receptor) | 4 | 1 | 0 | 1 | 1 | 0 | 1 | 1

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: 25. 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 | 0.0031 | 2e-09 | 1.2e-06
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 | 5.2e-09 | 1.6e-06
3 | 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 | 2e-08 | 4.1e-06
4 | 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 | 6.7e-08 | 1e-05
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 | 2.7e-07 | 0.000033
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 | 9.2e-07 | 0.000095
7 | 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 | 1.3e-06 | 0.00011
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 | 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 | 5.7e-06 | 0.00042
9 | 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 | 6.1e-06 | 0.00042
10 | 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(3), PIK3R1(1), RB1(2), TP53(14) | 860636 | 21 | 13 | 19 | 2 | 5 | 1 | 9 | 1 | 4 | 1 | 0.077 | 0.000017 | 0.0011

Table 7. Get Full Table A Ranked List of Significantly Mutated Genesets (Excluding Significantly Mutated Genes). Number of significant genesets found: 4. 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 | 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 | 0.00033 | 0.094
2 | 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 | 0.00047 | 0.094
3 | 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 | 0.00054 | 0.094
4 | FBW7PATHWAY | Cyclin E interacts with cell cycle checkpoint kinase cdk2 to allow transcription of genes required for S phase, including transcription of additional cyclin E. | CCNE1, CDC34, CDK2, CUL1, E2F1, FBXW7, RB1, SKP1A, TFDP1 | 7 | CUL1(4), RB1(2) | 281792 | 6 | 6 | 4 | 0 | 3 | 0 | 1 | 0 | 1 | 1 | 0.2 | 0.00061 | 0.094
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 | 0.0016 | 0.16
6 | 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 | 0.002 | 0.16
7 | 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 | 0.0023 | 0.16
8 | 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 | 0.48 | 0.0023 | 0.16
9 | 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 | 0.0025 | 0.16
10 | TPOPATHWAY | Thrombopoietin binds to its receptor and activates cell growth through the Erk and JNK MAP kinase pathways, protein kinase C, and JAK/STAT activation. | CSNK2A1, FOS, GRB2, HRAS, JAK2, JUN, MAP2K1, MAPK3, MPL, PIK3CA, PIK3R1, PLCG1, PRKCA, PRKCB1, RAF1, RASA1, SHC1, SOS1, STAT1, STAT3, STAT5A, STAT5B, THPO | 22 | CSNK2A1(1), FOS(1), JAK2(1), MAP2K1(1), MPL(1), PIK3CA(3), PIK3R1(1), PLCG1(2), RASA1(1), SOS1(2), STAT1(1), STAT5B(1) | 1257648 | 16 | 14 | 16 | 0 | 10 | 1 | 4 | 1 | 0 | 0 | 0.016 | 0.0028 | 0.16

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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