Prostate Adenocarcinoma: 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: PRAD

- 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.final_analysis_set.maf

- Significantly mutated genes (q ≤ 0.1): 56

- Mutations seen in COSMIC: 28

- Significantly mutated genes in COSMIC territory: 7

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

- Significantly mutated genesets: 3

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

Mutation Preprocessing

- Read 83 MAFs of type "Broad"

- Total number of mutations in input MAFs: 12281

- After removing 28 mutations outside chr1-24: 12253

- After removing 6658 noncoding mutations: 5595

- After collapsing adjacent/redundant mutations: 5566

Mutation Filtering

- Number of mutations before filtering: 5566

- After removing 203 mutations outside gene set: 5363

- After removing 4 mutations outside category set: 5359

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 | 3284
Nonsense_Mutation | 183
Nonstop_Mutation | 2
Silent | 1484
Splice_Site | 102
Translation_Start_Site | 13
Total | 5359

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 | 839 | 138713067 | 6e-06 | 6 | 3.9 | 2.1
*Np(A/C/T)->transit | 898 | 1965699488 | 4.6e-07 | 0.46 | 0.29 | 2
*ApG->G | 107 | 381313535 | 2.8e-07 | 0.28 | 0.18 | 2.1
transver | 1447 | 2485726090 | 5.8e-07 | 0.58 | 0.37 | 5
indel+null | 581 | 2485726090 | 2.3e-07 | 0.23 | 0.15 | NaN
double_null | 3 | 2485726090 | 1.2e-09 | 0.0012 | 0.00077 | NaN
Total | 3875 | 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.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: *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

- 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: 56. 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 | POM121 | POM121 membrane glycoprotein (rat) | 216520 | 3 | 3 | 1 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 0.0037 | 0.48 | 6e-07 | 0.33 | 0 | <1.00e-15 | <9.07e-12
2 | ZNF285 |  | 148155 | 4 | 3 | 2 | 1 | 0 | 0 | 2 | 2 | 0 | 0 | 0.000058 | 0.74 | 1.8e-06 | 1.8e-06 | 0 | <1.00e-15 | <9.07e-12
3 | MUC4 | mucin 4, cell surface associated | 272535 | 15 | 13 | 9 | 2 | 3 | 4 | 0 | 8 | 0 | 0 | 9.2e-13 | 0.13 | 0.00036 | 0.1 | 0.0002 | 6.77e-15 | 4.09e-11
4 | C9orf150 | chromosome 9 open reading frame 150 | 47265 | 3 | 3 | 1 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 2e-06 | 1 | 3.6e-06 | 0.99 | 8.6e-06 | 4.51e-10 | 1.98e-06
5 | NKX3-1 | NK3 homeobox 1 | 43527 | 5 | 5 | 5 | 0 | 0 | 2 | 0 | 2 | 1 | 0 | 3.6e-09 | 0.26 | 0.044 | 0.0026 | 0.0059 | 5.45e-10 | 1.98e-06
6 | FIP1L1 | FIP1 like 1 (S. cerevisiae) | 152119 | 3 | 3 | 1 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 0.00016 | 1 | 2e-07 | 1 | 1.2e-06 | 4.40e-09 | 0.000013
7 | 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 | 6.4e-06 | 0.33 | 7e-06 | 6.86e-09 | 0.000018
8 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | 122342 | 3 | 3 | 1 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 0.00064 | 0.53 | 6e-07 | 1 | 1.8e-06 | 2.49e-08 | 0.000056
9 | CCNF | cyclin F | 199411 | 3 | 3 | 1 | 1 | 0 | 0 | 0 | 3 | 0 | 0 | 0.0035 | 0.79 | 6e-07 | 0.023 | 6e-07 | 4.37e-08 | 0.000088
10 | DUSP27 | dual specificity phosphatase 27 (putative) | 264959 | 3 | 3 | 1 | 1 | 0 | 0 | 0 | 3 | 0 | 0 | 0.0025 | 0.82 | 2e-07 | 0.92 | 1.2e-06 | 6.26e-08 | 0.00011
11 | CLSTN1 | calsyntenin 1 | 242387 | 3 | 3 | 1 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 0.0084 | 0.6 | 4e-07 | 0.052 | 4e-07 | 6.90e-08 | 0.00011
12 | TP53 | tumor protein p53 | 105521 | 5 | 5 | 5 | 0 | 3 | 0 | 0 | 1 | 1 | 0 | 8.3e-07 | 0.33 | 0.069 | 0.0012 | 0.0056 | 9.31e-08 | 0.00014
13 | TPTE2 | transmembrane phosphoinositide 3-phosphatase and tensin homolog 2 | 136261 | 6 | 6 | 6 | 1 | 1 | 2 | 0 | 2 | 1 | 0 | 6.3e-09 | 0.48 | 0.8 | 0.55 | 0.89 | 1.12e-07 | 0.00016
14 | FRG1 | FSHD region gene 1 | 67208 | 6 | 5 | 4 | 0 | 0 | 2 | 0 | 3 | 1 | 0 | 1.2e-08 | 0.32 | 0.31 | 1 | 0.51 | 1.21e-07 | 0.00016
15 | SLC2A6 | solute carrier family 2 (facilitated glucose transporter), member 6 | 97622 | 2 | 2 | 1 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0.0026 | 0.61 | 0.00086 | 0.000013 | 9.8e-06 | 4.65e-07 | 0.00055
16 | ZNF492 | zinc finger protein 492 | 123622 | 4 | 4 | 3 | 0 | 0 | 3 | 0 | 1 | 0 | 0 | 2e-05 | 0.28 | 0.00028 | 0.57 | 0.0013 | 4.88e-07 | 0.00055
17 | YBX1 | Y box binding protein 1 | 68945 | 4 | 3 | 2 | 0 | 0 | 2 | 0 | 2 | 0 | 0 | 0.00015 | 0.32 | 0.0082 | 0.00043 | 0.0002 | 5.35e-07 | 0.00057
18 | SPOP | speckle-type POZ protein | 96345 | 4 | 4 | 3 | 0 | 0 | 0 | 1 | 3 | 0 | 0 | 5.1e-06 | 0.39 | 0.0072 | 0.27 | 0.0091 | 8.26e-07 | 0.00083
19 | ARHGAP11B | Rho GTPase activating protein 11B | 68637 | 4 | 4 | 2 | 0 | 0 | 0 | 0 | 1 | 3 | 0 | 1.3e-06 | 0.25 | NaN | NaN | NaN | 1.25e-06 | 0.0012
20 | SCAI |  | 157950 | 5 | 5 | 2 | 0 | 0 | 0 | 0 | 5 | 0 | 0 | 3.2e-06 | 0.45 | 0.012 | 0.4 | 0.028 | 1.53e-06 | 0.0014
21 | 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 | 0.079 | 0.96 | 0.24 | 5.46e-06 | 0.0047
22 | ETV3 | ets variant gene 3 | 36841 | 2 | 2 | 2 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0.00063 | 0.65 | 0.00065 | 0.42 | 0.00065 | 6.43e-06 | 0.0053
23 | ZNF814 | zinc finger protein 814 | 168858 | 4 | 4 | 2 | 0 | 0 | 2 | 0 | 2 | 0 | 0 | 6e-05 | 0.34 | 0.002 | 0.99 | 0.011 | 0.000010 | 0.0080
24 | GPATCH4 | G patch domain containing 4 | 97579 | 2 | 2 | 1 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0.0018 | 1 | 0.00086 | 0.28 | 0.00051 | 0.000014 | 0.011
25 | CTNNB1 | catenin (cadherin-associated protein), beta 1, 88kDa | 199245 | 3 | 3 | 3 | 0 | 0 | 1 | 0 | 2 | 0 | 0 | 0.0015 | 0.46 | 0.00068 | 0.24 | 0.00082 | 0.000018 | 0.013
26 | 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 | 0.000027 | 0.019
27 | PDE4DIP | phosphodiesterase 4D interacting protein (myomegalin) | 720610 | 6 | 6 | 5 | 1 | 0 | 2 | 3 | 0 | 1 | 0 | 0.00011 | 0.4 | 0.0082 | 0.84 | 0.019 | 0.000029 | 0.019
28 | PRR21 |  | 58941 | 4 | 4 | 4 | 0 | 1 | 1 | 0 | 2 | 0 | 0 | 3.2e-06 | 0.26 | 0.24 | 0.94 | 0.69 | 0.000031 | 0.020
29 | SLC15A3 | solute carrier family 15, member 3 | 101449 | 2 | 2 | 1 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0.0079 | 0.66 | 0.00075 | 0.066 | 0.00033 | 0.000036 | 0.023
30 | GOLGA6B | golgi autoantigen, golgin subfamily a, 6B | 88280 | 2 | 2 | 1 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0.001 | 0.37 | 0.0012 | 0.86 | 0.0034 | 0.000047 | 0.029
31 | FNBP4 | formin binding protein 4 | 236598 | 2 | 2 | 1 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0.013 | 1 | 0.00033 | 0.95 | 0.00033 | 0.000057 | 0.034
32 | NOTCH2NL | Notch homolog 2 (Drosophila) N-terminal like | 60118 | 3 | 3 | 2 | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 0.000061 | 0.3 | NaN | NaN | NaN | 0.000061 | 0.034
33 | OR4A16 | olfactory receptor, family 4, subfamily A, member 16 | 82009 | 2 | 2 | 2 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0.0026 | 0.54 | 0.22 | 0.0024 | 0.002 | 0.000067 | 0.037
34 | ANKRD36 | ankyrin repeat domain 36 | 204931 | 4 | 4 | 2 | 1 | 0 | 0 | 0 | 4 | 0 | 0 | 0.00018 | 0.71 | 0.011 | 0.82 | 0.032 | 0.000075 | 0.040
35 | PRIM2 | primase, DNA, polypeptide 2 (58kDa) | 120943 | 4 | 4 | 2 | 4 | 0 | 0 | 0 | 1 | 3 | 0 | 0.000077 | 1 | NaN | NaN | NaN | 0.000077 | 0.040

POM121

Figure S1. This figure depicts the distribution of mutations and mutation types across the POM121 significant gene.

ZNF285

Figure S2. This figure depicts the distribution of mutations and mutation types across the ZNF285 significant gene.

MUC4

Figure S3. This figure depicts the distribution of mutations and mutation types across the MUC4 significant gene.

C9orf150

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

NKX3-1

Figure S5. This figure depicts the distribution of mutations and mutation types across the NKX3-1 significant gene.

FIP1L1

Figure S6. This figure depicts the distribution of mutations and mutation types across the FIP1L1 significant gene.

NDUFS4

Figure S7. This figure depicts the distribution of mutations and mutation types across the NDUFS4 significant gene.

AGT

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

CCNF

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

DUSP27

Figure S10. This figure depicts the distribution of mutations and mutation types across the DUSP27 significant gene.

CLSTN1

Figure S11. This figure depicts the distribution of mutations and mutation types across the CLSTN1 significant gene.

TP53

Figure S12. This figure depicts the distribution of mutations and mutation types across the TP53 significant gene.

TPTE2

Figure S13. This figure depicts the distribution of mutations and mutation types across the TPTE2 significant gene.

FRG1

Figure S14. This figure depicts the distribution of mutations and mutation types across the FRG1 significant gene.

SLC2A6

Figure S15. This figure depicts the distribution of mutations and mutation types across the SLC2A6 significant gene.

ZNF492

Figure S16. This figure depicts the distribution of mutations and mutation types across the ZNF492 significant gene.

YBX1

Figure S17. This figure depicts the distribution of mutations and mutation types across the YBX1 significant gene.

SPOP

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

ARHGAP11B

Figure S19. This figure depicts the distribution of mutations and mutation types across the ARHGAP11B significant gene.

SCAI

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

LILRB3

Figure S21. This figure depicts the distribution of mutations and mutation types across the LILRB3 significant gene.

ETV3

Figure S22. This figure depicts the distribution of mutations and mutation types across the ETV3 significant gene.

ZNF814

Figure S23. This figure depicts the distribution of mutations and mutation types across the ZNF814 significant gene.

GPATCH4

Figure S24. This figure depicts the distribution of mutations and mutation types across the GPATCH4 significant gene.

CTNNB1

Figure S25. This figure depicts the distribution of mutations and mutation types across the CTNNB1 significant gene.

C17orf63

Figure S26. This figure depicts the distribution of mutations and mutation types across the C17orf63 significant gene.

PDE4DIP

Figure S27. This figure depicts the distribution of mutations and mutation types across the PDE4DIP significant gene.

PRR21

Figure S28. This figure depicts the distribution of mutations and mutation types across the PRR21 significant gene.

SLC15A3

Figure S29. This figure depicts the distribution of mutations and mutation types across the SLC15A3 significant gene.

GOLGA6B

Figure S30. This figure depicts the distribution of mutations and mutation types across the GOLGA6B significant gene.

FNBP4

Figure S31. This figure depicts the distribution of mutations and mutation types across the FNBP4 significant gene.

NOTCH2NL

Figure S32. This figure depicts the distribution of mutations and mutation types across the NOTCH2NL significant gene.

OR4A16

Figure S33. This figure depicts the distribution of mutations and mutation types across the OR4A16 significant gene.

ANKRD36

Figure S34. This figure depicts the distribution of mutations and mutation types across the ANKRD36 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 | 308 | 5 | 25564 | 1608 | 8.1e-10 | 3.7e-06
2 | CHEK2 | CHK2 checkpoint homolog (S. pombe) | 2 | 2 | 2 | 166 | 2 | 3.3e-08 | 0.000075
3 | CTNNB1 | catenin (cadherin-associated protein), beta 1, 88kDa | 3 | 101 | 3 | 8383 | 1229 | 3.7e-07 | 0.00056
4 | ACSM2B | acyl-CoA synthetase medium-chain family member 2B | 1 | 1 | 1 | 83 | 1 | 0.00013 | 0.084
5 | BRE | brain and reproductive organ-expressed (TNFRSF1A modulator) | 1 | 1 | 1 | 83 | 1 | 0.00013 | 0.084
6 | KCNH1 | potassium voltage-gated channel, subfamily H (eag-related), member 1 | 1 | 1 | 1 | 83 | 1 | 0.00013 | 0.084
7 | PTEN | phosphatase and tensin homolog (mutated in multiple advanced cancers 1) | 3 | 728 | 3 | 60424 | 15 | 0.00013 | 0.084
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 | PIK3CA | phosphoinositide-3-kinase, catalytic, alpha polypeptide | 2 | 184 | 2 | 15272 | 355 | 0.00028 | 0.13

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: 3. 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 | 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 | 0 | 3 | 6 | 0 | 2 | 1 | 0 | 0.032 | 0.000053 | 0.016
3 | 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 | 0.00035 | 0.072
4 | 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 | 0.001 | 0.15
5 | 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 | 0.0015 | 0.18
6 | 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
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 | 0.19 | 0.0033 | 0.29
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 | 0.0057 | 0.39
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 | 0.0057 | 0.39
10 | ATRBRCAPATHWAY | BRCA1 and 2 block cell cycle progression in response to DNA damage and promote double-stranded break repair; mutations induce breast cancer susceptibility. | ATM, ATR, BRCA1, BRCA2, CHEK1, CHEK2, FANCA, FANCC, FANCD2, FANCE, FANCF, FANCG, HUS1, MRE11A, NBS1, RAD1, RAD17, RAD50, RAD51, RAD9A, TP53, TREX1 | 21 | ATM(5), BRCA2(3), CHEK2(2), FANCD2(2), FANCG(1), TP53(5) | 5495234 | 18 | 15 | 16 | 1 | 3 | 6 | 0 | 6 | 3 | 0 | 0.061 | 0.0066 | 0.4

Table 6. 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 | 0.001 | 0.62
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 | 0.0073 | 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 | 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
5 | 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
6 | 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
7 | 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
8 | 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 | 0.031 | 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 | 0.032 | 1
10 | ST_PHOSPHOINOSITIDE_3_KINASE_PATHWAY | The phosphoinositide-3 kinase pathway produces the lipid second messenger PIP3 and regulates cell growth, survival, and movement. | A1BG, AKT1, AKT2, AKT3, BAD, BTK, CDKN2A, CSL4, DAF, DAPP1, FOXO1A, GRB2, GSK3A, GSK3B, IARS, IGFBP1, INPP5D, P14, PDK1, PIK3CA, PPP1R13B, PSCD3, PTEN, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KB1, SFN, SHC1, SOS1, SOS2, TEC, YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ, YWHAZ | 33 | A1BG(1), AKT1(1), BTK(1), GSK3A(1), PDK1(1), PIK3CA(2), PPP1R13B(1), PTEN(3) | 4518736 | 11 | 11 | 11 | 1 | 1 | 3 | 1 | 4 | 2 | 0 | 0.16 | 0.04 | 1

Methods & Data
Methods

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

Download Results

This is an experimental feature. The full results of the analysis summarized in this report can be downloaded from the TCGA Data Coordination Center.

- Analysis Results (MD5 checksum)

- Auxiliary Data (MD5 checksum)

- MAGE-TAB File (MD5 checksum)

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