Mutation Analysis (MutSig v2.0)
Prostate Adenocarcinoma (Primary solid tumor)
23 September 2013 | analyses__2013_09_23
Maintainer Information
Citation Information
doi:10.7908/C15H7DMG
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/C15H7DMG
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: PRAD-TP

- Number of patients in set: 83

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:PRAD-TP.final_analysis_set.maf

- Significantly mutated genes (q ≤ 0.1): 34

- Mutations seen in COSMIC: 28

- Significantly mutated genes in COSMIC territory: 7

- Genes with clustered mutations (≤ 3 aa apart): 24

- Significantly mutated genesets: 1

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

Mutation Preprocessing

- Read 83 MAFs of type "Broad"

- Total number of mutations in input MAFs: 5917

- After removing 18 mutations outside chr1-24: 5899

- After removing 304 noncoding mutations: 5595

Mutation Filtering

- Number of mutations before filtering: 5595

- After removing 207 mutations outside gene set: 5388

- After removing 4 mutations outside category set: 5384

Results
Breakdown of Mutations by Type

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

type | count
--- | ---
Frame_Shift_Del | 150
Frame_Shift_Ins | 77
In_Frame_Del | 51
In_Frame_Ins | 13
Missense_Mutation | 3294
Nonsense_Mutation | 185
Nonstop_Mutation | 2
Silent | 1497
Splice_Site | 102
Translation_Start_Site | 13
Total | 5384

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
--- | --- | --- | --- | --- | --- | ---
*CpG->T | 840 | 138713067 | 6.1e-06 | 6.1 | 3.9 | 2.1
*Np(A/C/T)->transit | 901 | 1965699488 | 4.6e-07 | 0.46 | 0.29 | 2
*ApG->G | 107 | 381313535 | 2.8e-07 | 0.28 | 0.18 | 2.1
transver | 1456 | 2485726090 | 5.9e-07 | 0.59 | 0.37 | 5
indel+null | 580 | 2485726090 | 2.3e-07 | 0.23 | 0.15 | NaN
double_null | 3 | 2485726090 | 1.2e-09 | 0.0012 | 0.00077 | NaN
Total | 3887 | 2485726090 | 1.6e-06 | 1.6 | 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: PRAD-TP.patients.counts_and_rates.txt

Lego Plots

The mutation spectrum is depicted in the lego plots below in which the 96 possible mutation types are subdivided into six large blocks, color-coded to reflect the base substitution type. Each large block is further subdivided into the 16 possible pairs of 5' and 3' neighbors, as listed in the 4x4 trinucleotide context legend. The height of each block corresponds to the mutation frequency for that kind of mutation (counts of mutations normalized by the base coverage in a given bin). The shape of the spectrum is a signature for dominant mutational mechanisms in different tumor types.

Figure 3. Get High-res Image SNV Mutation rate lego plot for entire set. Each bin is normalized by base coverage for that bin. Colors represent the six SNV types on the upper right. The three-base context for each mutation is labeled in the 4x4 legend on the lower right. The fractional breakdown of SNV counts is shown in the pie chart on the upper left. If this figure is blank, not enough information was provided in the MAF to generate it.

Figure 4. Get High-res Image SNV Mutation rate lego plots for 4 slices of mutation allele fraction (0<=AF<0.1, 0.1<=AF<0.25, 0.25<=AF<0.5, & 0.5<=AF) . The color code and three-base context legends are the same as the previous figure. If this figure is blank, not enough information was provided in the MAF to generate it.

CoMut Plot

Figure 5. Get High-res Image The matrix in the center of the figure represents individual mutations in patient samples, color-coded by type of mutation, for the significantly mutated genes. The rate of synonymous and non-synonymous mutations is displayed at the top of the matrix. The barplot on the left of the matrix shows the number of mutations in each gene. The percentages represent the fraction of tumors with at least one mutation in the specified gene. The barplot to the right of the matrix displays the q-values for the most significantly mutated genes. The purple boxplots below the matrix (only displayed if required columns are present in the provided MAF) represent the distributions of allelic fractions observed in each sample. The plot at the bottom represents the base substitution distribution of individual samples, using the same categories that were used to calculate significance.

Significantly Mutated Genes

Column Descriptions:

- N = number of sequenced bases in this gene across the individual set

- n = number of (nonsilent) mutations in this gene across the individual set

- npat = number of patients (individuals) with at least one nonsilent mutation

- nsite = number of unique sites having a non-silent mutation

- nsil = number of silent mutations in this gene across the individual set

- n1 = number of nonsilent mutations of type: *CpG->T

- n2 = number of nonsilent mutations of type: *Np(A/C/T)->transit

- n3 = number of nonsilent mutations of type: *ApG->G

- n4 = number of nonsilent mutations of type: transver

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

rank | gene | description | N | n | npat | nsite | nsil | n1 | n2 | n3 | n4 | n5 | n6 | p_classic | p_ns_s | p_clust | p_cons | p_joint | p | q
--- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | ---
1 | ZNF285 | zinc finger protein 285 | 148155 | 4 | 3 | 2 | 1 | 0 | 0 | 2 | 2 | 0 | 0 | 0.000059 | 0.74 | 0.000012 | 1.8e-06 | 0 | <1.00e-15 | <1.81e-11
2 | MUC4 | mucin 4, cell surface associated | 272535 | 15 | 13 | 9 | 2 | 3 | 4 | 0 | 8 | 0 | 0 | 8.9e-13 | 0.13 | 0.01 | 0.098 | 0.079 | 2.19e-12 | 1.98e-08
3 | NKX3-1 | NK3 homeobox 1 | 43527 | 5 | 5 | 5 | 0 | 0 | 2 | 0 | 2 | 1 | 0 | 3.3e-09 | 0.26 | 0.12 | 0.011 | 0.032 | 2.47e-09 | 1.49e-05
4 | C9orf150 | chromosome 9 open reading frame 150 | 47265 | 3 | 3 | 1 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 2e-06 | 1 | 0.000095 | 1 | 0.0012 | 4.96e-08 | 0.000225
5 | FRG1 | FSHD region gene 1 | 67208 | 6 | 5 | 4 | 0 | 0 | 2 | 0 | 3 | 1 | 0 | 1.2e-08 | 0.32 | 0.32 | 1 | 0.5 | 1.15e-07 | 0.000313
6 | TP53 | tumor protein p53 | 105521 | 5 | 5 | 5 | 0 | 3 | 0 | 0 | 1 | 1 | 0 | 8.3e-07 | 0.34 | 0.076 | 0.0015 | 0.0069 | 1.15e-07 | 0.000313
7 | TPTE2 | transmembrane phosphoinositide 3-phosphatase and tensin homolog 2 | 136261 | 6 | 6 | 6 | 1 | 1 | 2 | 0 | 2 | 1 | 0 | 6.1e-09 | 0.48 | 0.8 | 0.58 | 1 | 1.21e-07 | 0.000313
8 | NDUFS4 | NADH dehydrogenase (ubiquinone) Fe-S protein 4, 18kDa (NADH-coenzyme Q reductase) | 45401 | 3 | 3 | 1 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 0.000043 | 0.58 | 0.000077 | 0.34 | 0.00019 | 1.61e-07 | 0.000365
9 | ZNF492 | zinc finger protein 492 | 123622 | 4 | 4 | 3 | 0 | 0 | 3 | 0 | 1 | 0 | 0 | 2e-05 | 0.28 | 0.00047 | 0.56 | 0.0018 | 6.70e-07 | 0.00135
10 | SPOP | speckle-type POZ protein | 96345 | 4 | 4 | 3 | 0 | 0 | 0 | 1 | 3 | 0 | 0 | 4.8e-06 | 0.39 | 0.008 | 0.3 | 0.0097 | 8.32e-07 | 0.00151
11 | SLC2A6 | solute carrier family 2 (facilitated glucose transporter), member 6 | 97622 | 2 | 2 | 1 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0.0025 | 0.61 | 0.012 | 0.000024 | 0.000024 | 1.04e-06 | 0.00171
12 | ARHGAP11B | Rho GTPase activating protein 11B | 68637 | 4 | 4 | 2 | 0 | 0 | 0 | 0 | 1 | 3 | 0 | 1.2e-06 | 0.25 | NaN | NaN | NaN | 1.17e-06 | 0.00176
13 | SCAI | suppressor of cancer cell invasion | 157950 | 5 | 5 | 2 | 0 | 0 | 0 | 0 | 5 | 0 | 0 | 3.2e-06 | 0.45 | 0.013 | 0.43 | 0.029 | 1.58e-06 | 0.00220
14 | LILRB3 | leukocyte immunoglobulin-like receptor, subfamily B (with TM and ITIM domains), member 3 | 120480 | 4 | 4 | 2 | 1 | 0 | 0 | 3 | 1 | 0 | 0 | 1.4e-06 | 0.6 | 0.087 | 0.96 | 0.16 | 3.59e-06 | 0.00465
15 | FIP1L1 | FIP1 like 1 (S. cerevisiae) | 152119 | 3 | 3 | 1 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 0.00015 | 1 | 8e-05 | 1 | 0.0017 | 4.31e-06 | 0.00521
16 | YBX1 | Y box binding protein 1 | 68945 | 4 | 3 | 2 | 0 | 0 | 2 | 0 | 2 | 0 | 0 | 0.00014 | 0.32 | 0.016 | 0.0069 | 0.0026 | 5.93e-06 | 0.00672
17 | ZNF814 | zinc finger protein 814 | 168858 | 4 | 4 | 2 | 0 | 0 | 2 | 0 | 2 | 0 | 0 | 0.000061 | 0.34 | 0.0031 | 0.99 | 0.012 | 1.09e-05 | 0.0116
18 | CCNF | cyclin F | 199411 | 3 | 3 | 1 | 1 | 0 | 0 | 0 | 3 | 0 | 0 | 0.0034 | 0.79 | 0.000086 | 0.029 | 0.00032 | 1.60e-05 | 0.0157
19 | CLSTN1 | calsyntenin 1 | 242387 | 3 | 3 | 1 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 0.0084 | 0.6 | 0.000081 | 0.07 | 0.00013 | 1.64e-05 | 0.0157
20 | PRR21 | proline rich 21 | 58941 | 4 | 4 | 4 | 0 | 1 | 1 | 0 | 2 | 0 | 0 | 3.2e-06 | 0.26 | 0.22 | 0.93 | 0.42 | 1.94e-05 | 0.0174
21 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | 122342 | 3 | 3 | 1 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 0.00067 | 0.53 | 0.000084 | 1 | 0.0021 | 2.02e-05 | 0.0174
22 | C17orf63 | chromosome 17 open reading frame 63 | 5972 | 2 | 2 | 1 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0.000027 | 0.65 | NaN | NaN | NaN | 2.66e-05 | 0.0220
23 | PDE4DIP | phosphodiesterase 4D interacting protein (myomegalin) | 720610 | 6 | 6 | 5 | 1 | 0 | 2 | 3 | 0 | 1 | 0 | 0.0001 | 0.4 | 0.0092 | 0.83 | 0.023 | 3.33e-05 | 0.0262
24 | CTNNB1 | catenin (cadherin-associated protein), beta 1, 88kDa | 199245 | 3 | 3 | 3 | 0 | 0 | 1 | 0 | 2 | 0 | 0 | 0.0016 | 0.46 | 0.0013 | 0.29 | 0.0022 | 4.84e-05 | 0.0365
25 | NOTCH2NL | Notch homolog 2 (Drosophila) N-terminal like | 60118 | 3 | 3 | 2 | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 0.000059 | 0.3 | NaN | NaN | NaN | 5.92e-05 | 0.0429
26 | PRIM2 | primase, DNA, polypeptide 2 (58kDa) | 120943 | 4 | 4 | 2 | 4 | 0 | 0 | 0 | 1 | 3 | 0 | 0.000073 | 1 | NaN | NaN | NaN | 7.27e-05 | 0.0507
27 | OR6N1 | olfactory receptor, family 6, subfamily N, member 1 | 78146 | 3 | 3 | 2 | 0 | 0 | 0 | 2 | 1 | 0 | 0 | 0.000013 | 0.46 | 0.36 | 0.52 | 0.52 | 8.74e-05 | 0.0586
28 | DUSP27 | dual specificity phosphatase 27 (putative) | 264959 | 3 | 3 | 1 | 1 | 0 | 0 | 0 | 3 | 0 | 0 | 0.0024 | 0.82 | 0.000086 | 0.92 | 0.0029 | 9.17e-05 | 0.0586
29 | POTEC | POTE ankyrin domain family, member C | 130537 | 3 | 3 | 2 | 0 | 2 | 1 | 0 | 0 | 0 | 0 | 0.00011 | 0.24 | 0.02 | 0.78 | 0.066 | 9.38e-05 | 0.0586
30 | LRIT2 | leucine-rich repeat, immunoglobulin-like and transmembrane domains 2 | 138107 | 4 | 4 | 3 | 0 | 1 | 2 | 0 | 1 | 0 | 0 | 0.000014 | 0.25 | 0.32 | 0.91 | 0.58 | 0.000106 | 0.0630
31 | POM121 | POM121 membrane glycoprotein (rat) | 216520 | 3 | 3 | 1 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 0.0037 | 0.48 | 9e-05 | 0.37 | 0.0023 | 0.000108 | 0.0630
32 | ANKRD36 | ankyrin repeat domain 36 | 204931 | 4 | 4 | 2 | 1 | 0 | 0 | 0 | 4 | 0 | 0 | 0.00018 | 0.71 | 0.019 | 0.84 | 0.049 | 0.000112 | 0.0635
33 | OR4D5 | olfactory receptor, family 4, subfamily D, member 5 | 79763 | 3 | 3 | 3 | 0 | 2 | 0 | 0 | 1 | 0 | 0 | 0.000017 | 0.46 | 0.79 | 0.3 | 0.56 | 0.000116 | 0.0639
34 | ZNF98 | zinc finger protein 98 (F7175) | 122162 | 4 | 4 | 4 | 0 | 0 | 1 | 0 | 2 | 1 | 0 | 0.000011 | 0.45 | 0.69 | 0.96 | 1 | 0.000141 | 0.0751
35 | OR4A16 | olfactory receptor, family 4, subfamily A, member 16 | 82009 | 2 | 2 | 2 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0.0025 | 0.54 | 0.23 | 0.0042 | 0.0074 | 0.000220 | 0.114

ZNF285

Figure S1. This figure depicts the distribution of mutations and mutation types across the ZNF285 significant gene.

MUC4

Figure S2. This figure depicts the distribution of mutations and mutation types across the MUC4 significant gene.

NKX3-1

Figure S3. This figure depicts the distribution of mutations and mutation types across the NKX3-1 significant gene.

C9orf150

Figure S4. This figure depicts the distribution of mutations and mutation types across the C9orf150 significant gene.

FRG1

Figure S5. This figure depicts the distribution of mutations and mutation types across the FRG1 significant gene.

TP53

Figure S6. This figure depicts the distribution of mutations and mutation types across the TP53 significant gene.

TPTE2

Figure S7. This figure depicts the distribution of mutations and mutation types across the TPTE2 significant gene.

NDUFS4

Figure S8. This figure depicts the distribution of mutations and mutation types across the NDUFS4 significant gene.

ZNF492

Figure S9. This figure depicts the distribution of mutations and mutation types across the ZNF492 significant gene.

SPOP

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

SLC2A6

Figure S11. This figure depicts the distribution of mutations and mutation types across the SLC2A6 significant gene.

ARHGAP11B

Figure S12. This figure depicts the distribution of mutations and mutation types across the ARHGAP11B significant gene.

SCAI

Figure S13. This figure depicts the distribution of mutations and mutation types across the SCAI significant gene.

LILRB3

Figure S14. This figure depicts the distribution of mutations and mutation types across the LILRB3 significant gene.

FIP1L1

Figure S15. This figure depicts the distribution of mutations and mutation types across the FIP1L1 significant gene.

YBX1

Figure S16. This figure depicts the distribution of mutations and mutation types across the YBX1 significant gene.

ZNF814

Figure S17. This figure depicts the distribution of mutations and mutation types across the ZNF814 significant gene.

CCNF

Figure S18. This figure depicts the distribution of mutations and mutation types across the CCNF significant gene.

CLSTN1

Figure S19. This figure depicts the distribution of mutations and mutation types across the CLSTN1 significant gene.

PRR21

Figure S20. This figure depicts the distribution of mutations and mutation types across the PRR21 significant gene.

AGT

Figure S21. This figure depicts the distribution of mutations and mutation types across the AGT significant gene.

C17orf63

Figure S22. This figure depicts the distribution of mutations and mutation types across the C17orf63 significant gene.

PDE4DIP

Figure S23. This figure depicts the distribution of mutations and mutation types across the PDE4DIP significant gene.

CTNNB1

Figure S24. This figure depicts the distribution of mutations and mutation types across the CTNNB1 significant gene.

NOTCH2NL

Figure S25. This figure depicts the distribution of mutations and mutation types across the NOTCH2NL significant gene.

PRIM2

Figure S26. This figure depicts the distribution of mutations and mutation types across the PRIM2 significant gene.

OR6N1

Figure S27. This figure depicts the distribution of mutations and mutation types across the OR6N1 significant gene.

DUSP27

Figure S28. This figure depicts the distribution of mutations and mutation types across the DUSP27 significant gene.

POTEC

Figure S29. This figure depicts the distribution of mutations and mutation types across the POTEC significant gene.

LRIT2

Figure S30. This figure depicts the distribution of mutations and mutation types across the LRIT2 significant gene.

POM121

Figure S31. This figure depicts the distribution of mutations and mutation types across the POM121 significant gene.

ANKRD36

Figure S32. This figure depicts the distribution of mutations and mutation types across the ANKRD36 significant gene.

OR4D5

Figure S33. This figure depicts the distribution of mutations and mutation types across the OR4D5 significant gene.

ZNF98

Figure S34. This figure depicts the distribution of mutations and mutation types across the ZNF98 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: 7. Number of genes displayed: 10

rank | gene | description | n | cos | n_cos | N_cos | cos_ev | p | q
--- | --- | --- | --- | --- | --- | --- | --- | --- | ---
1 | TP53 | tumor protein p53 | 5 | 356 | 5 | 29548 | 1608 | 1.7e-09 | 7.6e-06
2 | CHEK2 | CHK2 checkpoint homolog (S. pombe) | 2 | 2 | 2 | 166 | 2 | 3.3e-08 | 0.000076
3 | CTNNB1 | catenin (cadherin-associated protein), beta 1, 88kDa | 3 | 138 | 3 | 11454 | 1229 | 9.4e-07 | 0.0014
4 | ACSM2B | acyl-CoA synthetase medium-chain family member 2B | 1 | 1 | 1 | 83 | 1 | 0.00013 | 0.098
5 | BRE | brain and reproductive organ-expressed (TNFRSF1A modulator) | 1 | 1 | 1 | 83 | 1 | 0.00013 | 0.098
6 | KCNH1 | potassium voltage-gated channel, subfamily H (eag-related), member 1 | 1 | 1 | 1 | 83 | 1 | 0.00013 | 0.098
7 | PTEN | phosphatase and tensin homolog (mutated in multiple advanced cancers 1) | 3 | 767 | 3 | 63661 | 15 | 0.00015 | 0.099
8 | CHAT | choline acetyltransferase | 2 | 2 | 1 | 166 | 1 | 0.00026 | 0.13
9 | CYP4F2 | cytochrome P450, family 4, subfamily F, polypeptide 2 | 1 | 2 | 1 | 166 | 2 | 0.00026 | 0.13
10 | ACVR2A | activin A receptor, type IIA | 1 | 3 | 1 | 249 | 1 | 0.00039 | 0.16

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
--- | --- | --- | --- | --- | --- | --- | --- | --- | --- | ---
1657 | MUC4 | mucin 4, cell surface associated | 15 | 0 | 13 | 23 | 23 | 13 | 23 | 23
480 | CDC27 | cell division cycle 27 homolog (S. cerevisiae) | 10 | 0 | 6 | 8 | 9 | 6 | 8 | 9
2274 | SCAI | suppressor of cancer cell invasion | 5 | 0 | 6 | 6 | 6 | 6 | 6 | 6
92 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | 3 | 0 | 3 | 3 | 3 | 3 | 3 | 3
144 | ANKRD36 | ankyrin repeat domain 36 | 4 | 0 | 3 | 3 | 3 | 3 | 3 | 3
464 | CCNF | cyclin F | 3 | 0 | 3 | 3 | 3 | 3 | 3 | 3
563 | CLSTN1 | calsyntenin 1 | 3 | 0 | 3 | 3 | 3 | 3 | 3 | 3
624 | CROCC | ciliary rootlet coiled-coil, rootletin | 5 | 0 | 3 | 3 | 3 | 3 | 3 | 3
665 | CYP2D6 | cytochrome P450, family 2, subfamily D, polypeptide 6 | 4 | 0 | 3 | 3 | 3 | 3 | 3 | 3
779 | DUSP27 | dual specificity phosphatase 27 (putative) | 3 | 0 | 3 | 3 | 3 | 3 | 3 | 3

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: 1. 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 | 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 | CDKN1B(2), PRB1(3), TP53(5) | 1062488 | 10 | 10 | 10 | 0 | 3 | 1 | 0 | 3 | 3 | 0 | 0.12 | 6.4e-06 | 0.0039
2 | P53HYPOXIAPATHWAY | Hypoxia induces p53 accumulation and consequent apoptosis with p53-mediated cell cycle arrest, which is present under conditions of DNA damage. | ABCB1, AKT1, ATM, BAX, CDKN1A, CPB2, CSNK1A1, CSNK1D, FHL2, GADD45A, HIC1, HIF1A, HSPA1A, HSPCA, IGFBP3, MAPK8, MDM2, NFKBIB, NQO1, TP53 | 19 | ABCB1(2), AKT1(1), ATM(5), TP53(5) | 2602579 | 13 | 12 | 13 | 0 | 4 | 6 | 0 | 2 | 1 | 0 | 0.015 | 0.00034 | 0.1
3 | SA_REG_CASCADE_OF_CYCLIN_EXPR | Expression of cyclins regulates progression through the cell cycle by activating cyclin-dependent kinases. | CCNA1, CCNA2, CCND1, CCNE1, CCNE2, CDK2, CDK4, CDKN1B, CDKN2A, E2F1, E2F2, E2F4, PRB1 | 13 | CCNA1(1), CCNE2(1), CDKN1B(2), PRB1(3) | 1130432 | 7 | 7 | 7 | 0 | 0 | 2 | 0 | 3 | 2 | 0 | 0.25 | 0.00099 | 0.2
4 | 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 | APAF1(1), ATM(5), TP53(5) | 2266716 | 11 | 10 | 11 | 0 | 3 | 5 | 0 | 2 | 1 | 0 | 0.034 | 0.0014 | 0.22
5 | 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 | SP1(1), TP53(5) | 879118 | 6 | 6 | 6 | 0 | 3 | 1 | 0 | 1 | 1 | 0 | 0.16 | 0.0022 | 0.23
6 | 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(5), CHEK2(2), TP53(5) | 1994178 | 12 | 11 | 11 | 2 | 3 | 6 | 0 | 2 | 1 | 0 | 0.26 | 0.0022 | 0.23
7 | 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(5), TP53(5) | 2195302 | 10 | 9 | 10 | 1 | 3 | 4 | 0 | 2 | 1 | 0 | 0.18 | 0.0032 | 0.28
8 | 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 | ATM(5), CCNA1(1), CDKN1B(2), DHFR(1), TP53(5) | 3787641 | 14 | 12 | 14 | 0 | 3 | 5 | 0 | 2 | 4 | 0 | 0.032 | 0.0056 | 0.4
9 | CHEMICALPATHWAY | DNA damage promotes Bid cleavage, which stimulates mitochondrial cytochrome c release and consequent caspase activation, resulting in apoptosis. | ADPRT, AKT1, APAF1, ATM, BAD, BAX, BCL2, BCL2L1, BID, CASP3, CASP6, CASP7, CASP9, CYCS, EIF2S1, PRKCA, PRKCB1, PTK2, PXN, STAT1, TLN1, TP53 | 20 | AKT1(1), APAF1(1), ATM(5), TLN1(1), TP53(5) | 3433242 | 13 | 12 | 13 | 0 | 3 | 6 | 0 | 3 | 1 | 0 | 0.019 | 0.0058 | 0.4
10 | SMALL_LIGAND_GPCRS |  | C9orf47, CNR1, CNR2, DNMT1, EDG1, EDG2, EDG5, EDG6, MTNR1A, MTNR1B, PTAFR, PTGDR, PTGER1, PTGER2, PTGER4, PTGFR, PTGIR, TBXA2R | 13 | DNMT1(3), MTNR1A(1), PTGER2(1), TBXA2R(2) | 1410721 | 7 | 7 | 7 | 1 | 3 | 2 | 0 | 1 | 1 | 0 | 0.19 | 0.011 | 0.65

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 | SA_REG_CASCADE_OF_CYCLIN_EXPR | Expression of cyclins regulates progression through the cell cycle by activating cyclin-dependent kinases. | CCNA1, CCNA2, CCND1, CCNE1, CCNE2, CDK2, CDK4, CDKN1B, CDKN2A, E2F1, E2F2, E2F4, PRB1 | 13 | CCNA1(1), CCNE2(1), CDKN1B(2), PRB1(3) | 1130432 | 7 | 7 | 7 | 0 | 0 | 2 | 0 | 3 | 2 | 0 | 0.25 | 0.00099 | 0.61
2 | 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 | 14 | CDKN1B(2), PRB1(3) | 956967 | 5 | 5 | 5 | 0 | 0 | 1 | 0 | 2 | 2 | 0 | 0.45 | 0.0072 | 1
3 | SMALL_LIGAND_GPCRS |  | C9orf47, CNR1, CNR2, DNMT1, EDG1, EDG2, EDG5, EDG6, MTNR1A, MTNR1B, PTAFR, PTGDR, PTGER1, PTGER2, PTGER4, PTGFR, PTGIR, TBXA2R | 13 | DNMT1(3), MTNR1A(1), PTGER2(1), TBXA2R(2) | 1410721 | 7 | 7 | 7 | 1 | 3 | 2 | 0 | 1 | 1 | 0 | 0.19 | 0.011 | 1
4 | HSA00830_RETINOL_METABOLISM | Genes involved in retinol metabolism | ALDH1A1, ALDH1A2, BCMO1, RDH5 | 4 | ALDH1A2(1), BCMO1(2) | 483292 | 3 | 3 | 2 | 0 | 0 | 2 | 0 | 1 | 0 | 0 | 0.37 | 0.012 | 1
5 | 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 | AKT1(1), CDKN1B(2), PIK3CA(2), PTEN(3) | 2419782 | 8 | 8 | 8 | 1 | 0 | 3 | 1 | 1 | 3 | 0 | 0.36 | 0.013 | 1
6 | P53HYPOXIAPATHWAY | Hypoxia induces p53 accumulation and consequent apoptosis with p53-mediated cell cycle arrest, which is present under conditions of DNA damage. | ABCB1, AKT1, ATM, BAX, CDKN1A, CPB2, CSNK1A1, CSNK1D, FHL2, GADD45A, HIC1, HIF1A, HSPA1A, HSPCA, IGFBP3, MAPK8, MDM2, NFKBIB, NQO1, TP53 | 18 | ABCB1(2), AKT1(1), ATM(5) | 2497058 | 8 | 8 | 8 | 0 | 1 | 6 | 0 | 1 | 0 | 0 | 0.053 | 0.02 | 1
7 | HSA00670_ONE_CARBON_POOL_BY_FOLATE | Genes involved in one carbon pool by folate | ALDH1L1, AMT, ATIC, DHFR, FTCD, GART, MTFMT, MTHFD1, MTHFD1L, MTHFD2, MTHFR, MTHFS, MTR, SHMT1, SHMT2, TYMS | 16 | DHFR(1), FTCD(2), GART(1), MTHFD1(1), MTHFD1L(1), MTHFR(1) | 2365631 | 7 | 7 | 7 | 0 | 0 | 2 | 0 | 2 | 3 | 0 | 0.21 | 0.022 | 1
8 | LONGEVITYPATHWAY | Caloric restriction in animals often increases lifespan, which may occur via decreased IGF receptor expression and consequent expression of stress-resistance proteins. | AKT1, CAT, FOXO3A, GH1, GHR, HRAS, IGF1, IGF1R, PIK3CA, PIK3R1, SHC1, SOD1, SOD2, SOD3 | 13 | AKT1(1), GHR(1), IGF1R(1), PIK3CA(2), SOD3(1) | 1657357 | 6 | 6 | 6 | 0 | 0 | 4 | 1 | 1 | 0 | 0 | 0.12 | 0.023 | 1
9 | TRKAPATHWAY | Nerve growth factor (NGF) promotes neuronal survival and proliferation by binding its receptor TrkA, which activates PI3K/AKT, Ras, and the MAP kinase pathway. | AKT1, DPM2, GRB2, HRAS, KLK2, NGFB, NTRK1, PIK3CA, PIK3R1, PLCG1, PRKCA, PRKCB1, SHC1, SOS1 | 12 | AKT1(1), KLK2(1), NTRK1(2), PIK3CA(2) | 1940556 | 6 | 6 | 6 | 0 | 0 | 4 | 1 | 0 | 1 | 0 | 0.13 | 0.031 | 1
10 | HSA00564_GLYCEROPHOSPHOLIPID_METABOLISM | Genes involved in glycerophospholipid metabolism | ACHE, AGPAT1, AGPAT2, AGPAT3, AGPAT4, AGPAT6, ARD1A, CDIPT, CDS1, CDS2, CHAT, CHKA, CHKB, CHPT1, CRLS1, DGKA, DGKB, DGKD, DGKE, DGKG, DGKH, DGKI, DGKQ, DGKZ, ESCO1, ESCO2, ETNK1, ETNK2, GNPAT, GPAM, GPD1, GPD1L, GPD2, LCAT, LYCAT, LYPLA1, LYPLA2, LYPLA3, MYST3, MYST4, NAT5, NAT6, PCYT1A, PCYT1B, PEMT, PHOSPHO1, PISD, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, PLD1, PLD2, PNPLA3, PPAP2A, PPAP2B, PPAP2C, PTDSS1, PTDSS2, SH3GLB1 | 64 | AGPAT2(1), AGPAT3(1), CHAT(2), DGKD(1), DGKH(1), DGKI(1), DGKQ(2), ESCO1(3), GNPAT(1), MYST3(1), PEMT(1), PLA2G2A(1), PLA2G4A(1), PLA2G5(1), PLD1(1), PTDSS1(1) | 8241571 | 20 | 19 | 20 | 2 | 2 | 4 | 1 | 9 | 4 | 0 | 0.11 | 0.032 | 1

Methods & Data
Methods

In brief, we tabulate the number of mutations and the number of covered bases for each gene. The counts are broken down by mutation context category: four context categories that are discovered by MutSig, and one for indel and 'null' mutations, which include indels, nonsense mutations, splice-site mutations, and non-stop (read-through) mutations. For each gene, we calculate the probability of seeing the observed constellation of mutations, i.e. the product P1 x P2 x ... x Pm, or a more extreme one, given the background mutation rates calculated across the dataset. [1]

Download Results

In addition to the links below, the full results of the analysis summarized in this report can also be downloaded programmatically using firehose_get, or interactively from either the Broad GDAC website or TCGA Data Coordination Center Portal.

- Analysis Results (MD5 checksum)

- Auxiliary Data (MD5 checksum)

- MAGE-TAB File (MD5 checksum)

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