Bladder Urothelial Carcinoma: Mutation Analysis (MutSig v2.0)
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): 3

  • 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_ks = p-value for clustering of mutations (Kolmogorov-Smirnoff test)

  • 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: 3. 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 5.9e-15 0.025 0.000014 0.0018 0.000017 0 0
2 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 0.0027 0.056 0.0031 5.4e-07 0.0049
3 NFE2L2 nuclear factor (erythroid-derived 2)-like 2 50092 4 4 4 0 1 0 1 2 0 0 0.000016 0.4 0.26 0.0074 0.018 4.6e-06 0.028
4 KDM6A lysine (K)-specific demethylase 6A 116116 6 6 6 2 0 0 0 0 6 0 4.4e-06 0.98 0.84 0.38 0.88 0.000052 0.24
5 CUL1 cullin 1 67620 4 4 3 0 3 0 1 0 0 0 0.00041 0.37 0.57 0.006 0.019 0.0001 0.3
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 0.27 0.67 0.41 0.00011 0.3
7 GPS2 G protein pathway suppressor 2 28448 3 3 3 0 0 1 0 0 1 1 0.000015 0.57 0.39 0.41 0.63 0.00012 0.3
8 ARID1A AT rich interactive domain 1A (SWI-like) 162316 8 6 8 1 3 0 0 0 5 0 0.000051 0.66 0.16 0.89 0.27 0.00017 0.38
9 RAP1B RAP1B, member of RAS oncogene family 16212 2 2 2 0 1 0 0 1 0 0 0.0028 0.66 0.35 0.0092 0.0059 0.0002 0.39
10 MLL myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila) 327628 9 7 8 1 7 0 0 0 2 0 0.0029 0.48 0.0032 0.58 0.0066 0.00023 0.39
11 C9orf41 chromosome 9 open reading frame 41 28980 2 1 2 0 1 0 1 0 0 0 0.024 0.68 0.00085 0.63 0.00085 0.00024 0.39
12 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 0.91 0.013 0.19 0.00026 0.39
13 PYGO1 pygopus homolog 1 (Drosophila) 35616 3 3 3 0 0 0 1 1 1 0 0.00019 0.52 0.089 0.62 0.15 0.00033 0.42
14 HYI hydroxypyruvate isomerase homolog (E. coli) 15316 2 2 2 0 1 0 1 0 0 0 0.0016 0.55 0.019 0.8 0.019 0.00034 0.42
15 TMCO2 transmembrane and coiled-coil domains 2 15596 2 2 1 0 0 0 0 0 2 0 0.0019 1 0.0018 0.87 0.016 0.00035 0.42
16 AHCTF1 AT hook containing transcription factor 1 194544 2 2 2 0 1 0 1 0 0 0 0.25 0.73 0.00013 0.75 0.00013 0.00037 0.42
17 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 0.48 0.36 0.32 0.00039 0.42
18 C17orf81 chromosome 17 open reading frame 81 30464 3 2 3 1 2 0 1 0 0 0 0.0069 0.78 0.0076 0.08 0.007 0.00054 0.54
19 CREBBP CREB binding protein (Rubinstein-Taybi syndrome) 200396 5 5 5 1 0 0 2 0 3 0 0.0014 0.54 0.043 0.24 0.046 0.0007 0.64
20 NAA25 N(alpha)-acetyltransferase 25, NatB auxiliary subunit 82684 4 4 4 0 1 1 1 0 1 0 0.00031 0.44 0.11 0.84 0.21 0.0007 0.64
21 PLAUR plasminogen activator, urokinase receptor 29008 3 2 3 0 3 0 0 0 0 0 0.0087 0.38 0.0046 0.33 0.0082 0.00076 0.64
22 BCLAF1 BCL2-associated transcription factor 1 78596 5 4 5 0 2 0 0 2 1 0 0.00019 0.4 0.24 0.86 0.39 0.00078 0.64
23 HRNR hornerin 183680 6 6 6 0 2 1 2 1 0 0 0.00019 0.34 0.44 0.45 0.56 0.001 0.83
24 AMACR alpha-methylacyl-CoA racemase 36988 2 2 2 0 1 0 0 0 1 0 0.0099 0.82 0.03 0.2 0.012 0.0012 0.83
25 HLA-A major histocompatibility complex, class I, A 31220 3 3 3 0 0 0 1 0 2 0 0.00012 0.54 1 0.67 1 0.0012 0.83
26 SPG11 spastic paraplegia 11 (autosomal recessive) 206248 2 1 2 0 0 0 0 2 0 0 0.39 0.63 0.00031 0.53 0.00031 0.0012 0.83
27 PCDHAC1 protocadherin alpha subfamily C, 1 82096 4 4 4 0 1 0 1 2 0 0 0.00012 0.33 0.77 0.81 1 0.0012 0.83
28 LETMD1 LETM1 domain containing 1 31332 3 3 3 0 1 0 0 2 0 0 0.00057 0.42 0.83 0.097 0.24 0.0014 0.85
29 XPR1 xenotropic and polytropic retrovirus receptor 60228 5 4 5 1 3 0 0 0 2 0 0.00029 0.64 0.28 0.43 0.47 0.0014 0.85
30 OTUD7A OTU domain containing 7A 54404 4 4 4 0 3 0 1 0 0 0 0.0002 0.28 0.53 0.62 0.77 0.0015 0.87
31 RIMS3 regulating synaptic membrane exocytosis 3 26628 2 2 2 0 1 0 1 0 0 0 0.0022 0.47 0.019 0.61 0.077 0.0016 0.87
32 HMCN1 hemicentin 1 485408 9 8 9 0 4 0 1 2 2 0 0.0026 0.14 0.27 0.034 0.065 0.0016 0.87
33 C20orf20 chromosome 20 open reading frame 20 13524 2 2 2 1 1 0 0 1 0 0 0.0014 0.86 0.17 0.051 0.12 0.0017 0.87
34 CREB3L3 cAMP responsive element binding protein 3-like 3 39256 3 2 3 0 3 0 0 0 0 0 0.011 0.37 0.045 0.0078 0.016 0.0017 0.87
35 C11orf85 chromosome 11 open reading frame 85 19124 2 2 2 0 0 0 0 1 1 0 0.00047 0.58 0.18 0.89 0.39 0.0018 0.87
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.

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 2.9e-09 6.7e-06
3 FGFR3 fibroblast growth factor receptor 3 (achondroplasia, thanatophoric dwarfism) 2 43 2 1204 216 3e-05 0.045
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 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 3 184 2 5152 375 0.00054 0.27
9 IDH1 isocitrate dehydrogenase 1 (NADP+), soluble 1 3 1 84 1492 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

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.

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