Lung Squamous Cell Carcinoma: Mutation Analysis (MutSig)
Maintained by Dan DiCara (Broad Institute)
Overview
Introduction

This report serves to describe the mutational landscape and properties of a given individual set, as well as rank genes and genesets according to mutational significance. MutSig v2.0 was used to generate the results found in this report.

- Working with individual set: LUSC

- Number of patients in set: 178

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:LUSC.final_analysis_set.maf

- Significantly mutated genes (q ≤ 0.1): 132

- Mutations seen in COSMIC: 351

- Significantly mutated genes in COSMIC territory: 11

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

- Significantly mutated genesets: 18

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

Mutation Preprocessing

- Read 178 MAFs of type "Broad"

- Total number of mutations in input MAFs: 112274

- After removing 5 mutations outside chr1-24: 112269

- After removing 48505 noncoding mutations: 63764

- After collapsing adjacent/redundant mutations: 62900

Mutation Filtering

- Number of mutations before filtering: 62900

- After removing 361 mutations outside gene set: 62539

- After removing 32 mutations outside category set: 62507

Results
Breakdown of Mutations by Type

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

type | count
--- | ---
Frame_Shift_Del | 521
Frame_Shift_Ins | 134
In_Frame_Del | 84
In_Frame_Ins | 19
Missense_Mutation | 41821
Nonsense_Mutation | 3567
Nonstop_Mutation | 55
Silent | 15131
Splice_Site | 1152
Translation_Start_Site | 23
Total | 62507

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->mut | 12931 | 705628846 | 0.000018 | 18 | 2.1 | 3.3
(A/C/G)p*C->(A/T) | 16706 | 2005408876 | 8.3e-06 | 8.3 | 0.94 | 2.6
(A/C/G)p*C->G | 3292 | 2005408876 | 1.6e-06 | 1.6 | 0.18 | 4.9
A->mut | 8807 | 2607765148 | 3.4e-06 | 3.4 | 0.38 | 3.9
indel+null | 5610 | 5318802870 | 1.1e-06 | 1.1 | 0.12 | NaN
double_null | 30 | 5318802870 | 5.6e-09 | 0.0056 | 0.00063 | NaN
Total | 47376 | 5318802870 | 8.9e-06 | 8.9 | 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: LUSC.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->mut

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

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

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

- 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: 132. 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 | 223924 | 144 | 140 | 96 | 4 | 8 | 39 | 18 | 32 | 47 | 0 | <1.00e-15 | 6.7e-11 | 2e-07 | 2e-07 | 0 | <1.00e-15 | <4.52e-12
2 | NFE2L2 | nuclear factor (erythroid-derived 2)-like 2 | 318442 | 28 | 27 | 15 | 0 | 19 | 4 | 0 | 4 | 1 | 0 | <1.00e-15 | 0.0071 | 2e-07 | 2e-07 | 0 | <1.00e-15 | <4.52e-12
3 | PIK3CA | phosphoinositide-3-kinase, catalytic, alpha polypeptide | 585086 | 29 | 27 | 16 | 1 | 20 | 4 | 0 | 5 | 0 | 0 | 1.44e-12 | 0.021 | 0.000071 | 0.00075 | 0 | <1.00e-15 | <4.52e-12
4 | CDKN2A | cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) | 175686 | 26 | 26 | 23 | 1 | 5 | 5 | 2 | 2 | 12 | 0 | <1.00e-15 | 0.02 | 0.0019 | 2.2e-06 | 0 | <1.00e-15 | <4.52e-12
5 | TPTE | transmembrane phosphatase with tensin homology | 309720 | 30 | 24 | 29 | 2 | 10 | 4 | 2 | 9 | 5 | 0 | <1.00e-15 | 0.034 | 0.61 | 0.32 | 0.45 | <1.62e-14 | <5.87e-11
6 | KEAP1 | kelch-like ECH-associated protein 1 | 325562 | 23 | 21 | 21 | 0 | 9 | 8 | 2 | 2 | 2 | 0 | 2.35e-12 | 0.00032 | 0.058 | 0.21 | 0.077 | 5.50e-12 | 1.66e-08
7 | SI | sucrase-isomaltase (alpha-glucosidase) | 1009616 | 46 | 36 | 46 | 2 | 10 | 21 | 2 | 8 | 5 | 0 | 4.53e-12 | 0.0067 | 0.76 | 0.79 | 0.94 | 1.15e-10 | 2.98e-07
8 | PTEN | phosphatase and tensin homolog (mutated in multiple advanced cancers 1) | 222144 | 16 | 14 | 15 | 0 | 4 | 1 | 0 | 3 | 8 | 0 | 1.37e-10 | 0.11 | 0.037 | 0.37 | 0.064 | 2.33e-10 | 5.26e-07
9 | TRIM58 | tripartite motif-containing 58 | 197936 | 15 | 15 | 15 | 1 | 2 | 8 | 1 | 1 | 3 | 0 | 1.25e-09 | 0.053 | 0.01 | 0.47 | 0.03 | 9.38e-10 | 1.88e-06
10 | REG1B | regenerating islet-derived 1 beta (pancreatic stone protein, pancreatic thread protein) | 92738 | 11 | 11 | 9 | 1 | 6 | 2 | 0 | 2 | 1 | 0 | 2.04e-09 | 0.2 | 0.33 | 0.12 | 0.18 | 8.56e-09 | 0.000015
11 | OR5L2 | olfactory receptor, family 5, subfamily L, member 2 | 167320 | 15 | 13 | 15 | 1 | 0 | 6 | 3 | 5 | 1 | 0 | 8.07e-10 | 0.068 | 0.41 | 0.39 | 0.49 | 8.89e-09 | 0.000015
12 | LRRC4C | leucine rich repeat containing 4C | 343006 | 19 | 17 | 19 | 1 | 5 | 8 | 1 | 4 | 1 | 0 | 1.37e-08 | 0.021 | 0.073 | 0.17 | 0.075 | 2.22e-08 | 0.000034
13 | FAM5C | family with sequence similarity 5, member C | 414562 | 28 | 27 | 28 | 3 | 3 | 15 | 1 | 9 | 0 | 0 | 1.25e-09 | 0.043 | 1 | 0.96 | 1 | 2.68e-08 | 0.000037
14 | ZBBX | zinc finger, B-box domain containing | 440550 | 17 | 17 | 17 | 1 | 4 | 4 | 1 | 5 | 3 | 0 | 5.51e-08 | 0.13 | 0.023 | 0.65 | 0.038 | 4.37e-08 | 0.000056
15 | ELTD1 | EGF, latrophilin and seven transmembrane domain containing 1 | 375046 | 18 | 18 | 18 | 1 | 4 | 3 | 1 | 4 | 6 | 0 | 3.59e-09 | 0.081 | 0.46 | 0.78 | 0.68 | 5.10e-08 | 0.000062
16 | DPPA4 | developmental pluripotency associated 4 | 167854 | 12 | 12 | 12 | 0 | 4 | 3 | 1 | 0 | 4 | 0 | 8.80e-09 | 0.057 | 0.31 | 0.48 | 0.43 | 7.64e-08 | 0.000086
17 | ASB5 | ankyrin repeat and SOCS box-containing 5 | 181204 | 9 | 9 | 9 | 0 | 3 | 1 | 3 | 2 | 0 | 0 | 5.81e-06 | 0.14 | 0.013 | 0.0038 | 0.00074 | 8.70e-08 | 0.000093
18 | OR4M2 | olfactory receptor, family 4, subfamily M, member 2 | 168388 | 14 | 14 | 14 | 2 | 2 | 6 | 0 | 5 | 1 | 0 | 7.22e-09 | 0.2 | 0.93 | 0.8 | 1 | 1.43e-07 | 0.00014
19 | PDYN | prodynorphin | 137594 | 8 | 8 | 8 | 0 | 2 | 3 | 2 | 1 | 0 | 0 | 0.000020 | 0.09 | 0.0005 | 0.33 | 0.00063 | 2.44e-07 | 0.00023
20 | CYP11B1 | cytochrome P450, family 11, subfamily B, polypeptide 1 | 275544 | 15 | 15 | 15 | 1 | 0 | 11 | 1 | 3 | 0 | 0 | 1.25e-07 | 0.031 | 0.094 | 0.9 | 0.2 | 4.57e-07 | 0.00041
21 | OR2G6 | olfactory receptor, family 2, subfamily G, member 6 | 169990 | 15 | 15 | 15 | 3 | 3 | 5 | 0 | 7 | 0 | 0 | 3.86e-07 | 0.22 | 0.042 | 0.34 | 0.067 | 4.81e-07 | 0.00041
22 | CRB1 | crumbs homolog 1 (Drosophila) | 759882 | 27 | 23 | 27 | 2 | 8 | 6 | 1 | 9 | 3 | 0 | 1.25e-07 | 0.043 | 0.14 | 0.81 | 0.27 | 6.19e-07 | 0.00051
23 | KRTAP5-5 | keratin associated protein 5-5 | 120684 | 9 | 9 | 6 | 1 | 0 | 3 | 1 | 0 | 5 | 0 | 5.44e-07 | 0.53 | 0.023 | 1 | 0.069 | 6.84e-07 | 0.00054
24 | OR6F1 | olfactory receptor, family 6, subfamily F, member 1 | 165718 | 13 | 13 | 13 | 2 | 2 | 6 | 1 | 4 | 0 | 0 | 2.44e-07 | 0.19 | 0.32 | 0.14 | 0.18 | 7.95e-07 | 0.00060
25 | USP29 | ubiquitin specific peptidase 29 | 493594 | 18 | 17 | 18 | 1 | 3 | 6 | 2 | 4 | 3 | 0 | 2.21e-07 | 0.075 | 0.87 | 0.24 | 0.53 | 1.98e-06 | 0.0014
26 | ESRRG | estrogen-related receptor gamma | 250090 | 12 | 12 | 12 | 1 | 2 | 5 | 1 | 2 | 2 | 0 | 1.03e-06 | 0.13 | 0.082 | 0.5 | 0.12 | 2.17e-06 | 0.0015
27 | MAGEB2 | melanoma antigen family B, 2 | 129406 | 9 | 9 | 9 | 1 | 2 | 4 | 2 | 1 | 0 | 0 | 3.22e-07 | 0.27 | 0.6 | 0.45 | 0.57 | 3.03e-06 | 0.0020
28 | CFHR4 | complement factor H-related 4 | 181560 | 10 | 10 | 10 | 1 | 0 | 4 | 1 | 3 | 2 | 0 | 7.60e-07 | 0.35 | 0.41 | 0.36 | 0.44 | 5.38e-06 | 0.0035
29 | C20orf26 | chromosome 20 open reading frame 26 | 679426 | 21 | 19 | 21 | 1 | 4 | 11 | 1 | 3 | 2 | 0 | 7.76e-06 | 0.017 | 0.024 | 0.34 | 0.049 | 6.00e-06 | 0.0037
30 | SLC13A1 | solute carrier family 13 (sodium/sulfate symporters), member 1 | 328944 | 12 | 12 | 12 | 1 | 4 | 2 | 1 | 4 | 1 | 0 | 3.40e-06 | 0.15 | 0.066 | 0.51 | 0.12 | 6.36e-06 | 0.0038
31 | PNLIPRP3 | pancreatic lipase-related protein 3 | 258456 | 11 | 11 | 11 | 1 | 1 | 5 | 2 | 1 | 2 | 0 | 2.94e-06 | 0.38 | 0.13 | 0.22 | 0.15 | 6.90e-06 | 0.0040
32 | OR51B2 | olfactory receptor, family 51, subfamily B, member 2 | 167854 | 10 | 10 | 10 | 0 | 2 | 3 | 1 | 3 | 1 | 0 | 1.08e-06 | 0.077 | 0.37 | 0.36 | 0.47 | 7.86e-06 | 0.0044
33 | HS6ST1 | heparan sulfate 6-O-sulfotransferase 1 | 172838 | 5 | 5 | 5 | 0 | 1 | 2 | 0 | 0 | 2 | 0 | 0.014 | 0.12 | 0.00017 | 0.0058 | 0.000055 | 0.000011 | 0.0061
34 | REG3G | regenerating islet-derived 3 gamma | 97544 | 8 | 8 | 8 | 1 | 1 | 3 | 0 | 0 | 4 | 0 | 1.23e-06 | 0.26 | 0.47 | 0.42 | 0.64 | 0.000012 | 0.0061
35 | CPS1 | carbamoyl-phosphate synthetase 1, mitochondrial | 832506 | 27 | 24 | 26 | 2 | 4 | 14 | 1 | 6 | 2 | 0 | 3.69e-06 | 0.025 | 0.13 | 0.9 | 0.21 | 0.000012 | 0.0061

TP53

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

NFE2L2

Figure S2. This figure depicts the distribution of mutations and mutation types across the NFE2L2 significant gene.

PIK3CA

Figure S3. This figure depicts the distribution of mutations and mutation types across the PIK3CA significant gene.

CDKN2A

Figure S4. This figure depicts the distribution of mutations and mutation types across the CDKN2A significant gene.

TPTE

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

KEAP1

Figure S6. This figure depicts the distribution of mutations and mutation types across the KEAP1 significant gene.

SI

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

PTEN

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

TRIM58

Figure S9. This figure depicts the distribution of mutations and mutation types across the TRIM58 significant gene.

REG1B

Figure S10. This figure depicts the distribution of mutations and mutation types across the REG1B significant gene.

OR5L2

Figure S11. This figure depicts the distribution of mutations and mutation types across the OR5L2 significant gene.

LRRC4C

Figure S12. This figure depicts the distribution of mutations and mutation types across the LRRC4C significant gene.

FAM5C

Figure S13. This figure depicts the distribution of mutations and mutation types across the FAM5C significant gene.

ZBBX

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

ELTD1

Figure S15. This figure depicts the distribution of mutations and mutation types across the ELTD1 significant gene.

DPPA4

Figure S16. This figure depicts the distribution of mutations and mutation types across the DPPA4 significant gene.

ASB5

Figure S17. This figure depicts the distribution of mutations and mutation types across the ASB5 significant gene.

OR4M2

Figure S18. This figure depicts the distribution of mutations and mutation types across the OR4M2 significant gene.

CYP11B1

Figure S19. This figure depicts the distribution of mutations and mutation types across the CYP11B1 significant gene.

OR2G6

Figure S20. This figure depicts the distribution of mutations and mutation types across the OR2G6 significant gene.

CRB1

Figure S21. This figure depicts the distribution of mutations and mutation types across the CRB1 significant gene.

KRTAP5-5

Figure S22. This figure depicts the distribution of mutations and mutation types across the KRTAP5-5 significant gene.

OR6F1

Figure S23. This figure depicts the distribution of mutations and mutation types across the OR6F1 significant gene.

USP29

Figure S24. This figure depicts the distribution of mutations and mutation types across the USP29 significant gene.

ESRRG

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

MAGEB2

Figure S26. This figure depicts the distribution of mutations and mutation types across the MAGEB2 significant gene.

CFHR4

Figure S27. This figure depicts the distribution of mutations and mutation types across the CFHR4 significant gene.

C20orf26

Figure S28. This figure depicts the distribution of mutations and mutation types across the C20orf26 significant gene.

SLC13A1

Figure S29. This figure depicts the distribution of mutations and mutation types across the SLC13A1 significant gene.

PNLIPRP3

Figure S30. This figure depicts the distribution of mutations and mutation types across the PNLIPRP3 significant gene.

OR51B2

Figure S31. This figure depicts the distribution of mutations and mutation types across the OR51B2 significant gene.

HS6ST1

Figure S32. This figure depicts the distribution of mutations and mutation types across the HS6ST1 significant gene.

REG3G

Figure S33. This figure depicts the distribution of mutations and mutation types across the REG3G 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: 11. Number of genes displayed: 10

rank | gene | description | n | cos | n_cos | N_cos | cos_ev | p | q
--- | --- | --- | --- | --- | --- | --- | --- | --- | ---
1 | PIK3CA | phosphoinositide-3-kinase, catalytic, alpha polypeptide | 29 | 184 | 24 | 32752 | 9572 | 1.2e-12 | 2.5e-09
2 | TP53 | tumor protein p53 | 144 | 308 | 141 | 54824 | 25449 | 1.7e-12 | 2.5e-09
3 | CDKN2A | cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) | 26 | 315 | 25 | 56070 | 559 | 1.7e-12 | 2.5e-09
4 | PTEN | phosphatase and tensin homolog (mutated in multiple advanced cancers 1) | 16 | 728 | 16 | 129584 | 579 | 2.2e-12 | 2.5e-09
5 | FBXW7 | F-box and WD repeat domain containing 7 | 11 | 91 | 6 | 16198 | 220 | 1.1e-08 | 1e-05
6 | HRAS | v-Ha-ras Harvey rat sarcoma viral oncogene homolog | 4 | 19 | 4 | 3382 | 802 | 3.3e-08 | 0.000025
7 | RB1 | retinoblastoma 1 (including osteosarcoma) | 12 | 267 | 7 | 47526 | 17 | 3.3e-07 | 0.00022
8 | HEPACAM2 |  | 4 | 1 | 2 | 178 | 2 | 1.2e-06 | 0.00071
9 | NF1 | neurofibromin 1 (neurofibromatosis, von Recklinghausen disease, Watson disease) | 22 | 285 | 6 | 50730 | 21 | 8e-06 | 0.004
10 | BRAF | v-raf murine sarcoma viral oncogene homolog B1 | 8 | 88 | 4 | 15664 | 77 | 0.000014 | 0.0064

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: 18. 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 | G1PATHWAY | CDK4/6-cyclin D and CDK2-cyclin E phosphorylate Rb, which allows the transcription of genes needed for the G1/S cell cycle transition. | ABL1, ATM, ATR, CCNA1, CCND1, CCNE1, CDC2, CDC25A, CDK2, CDK4, CDK6, CDKN1A, CDKN1B, CDKN2A, CDKN2B, DHFR, E2F1, GSK3B, HDAC1, MADH3, MADH4, RB1, SKP2, TFDP1, TGFB1, TGFB2, TGFB3, TP53 | 25 | ABL1(3), ATM(8), ATR(13), CCNA1(1), CCND1(1), CCNE1(3), CDKN1A(2), CDKN2A(26), CDKN2B(1), E2F1(2), HDAC1(2), RB1(12), SKP2(2), TFDP1(3), TGFB1(1), TGFB2(3), TP53(144) | 8137626 | 227 | 156 | 176 | 13 | 28 | 65 | 23 | 40 | 71 | 0 | 5.9e-11 | <1.00e-15 | <4.40e-14
2 | 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(3), CDKN2A(26), E2F1(2), MDM2(2), MYC(1), PIK3CA(29), PIK3R1(2), POLR1A(3), POLR1B(2), POLR1D(1), RAC1(1), RB1(12), TBX2(3), TP53(144) | 5471186 | 231 | 155 | 167 | 15 | 42 | 56 | 20 | 44 | 69 | 0 | 5.9e-11 | <1.00e-15 | <4.40e-14
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(17), AKT1(1), ATM(8), BAX(1), CDKN1A(2), CPB2(3), CSNK1A1(2), CSNK1D(2), FHL2(1), GADD45A(1), HIF1A(1), IGFBP3(2), MAPK8(2), MDM2(2), NFKBIB(1), TP53(144) | 5574960 | 190 | 150 | 142 | 8 | 26 | 53 | 19 | 40 | 51 | 1 | 4.3e-11 | <1.00e-15 | <4.40e-14
4 | 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(4), ATM(8), BAX(1), BCL2L1(1), CASP7(2), CASP9(3), PRKCA(5), PTK2(6), PXN(3), STAT1(2), TLN1(6), TP53(144) | 7347662 | 186 | 148 | 137 | 16 | 24 | 51 | 22 | 40 | 49 | 0 | 8.4e-07 | <1.00e-15 | <4.40e-14
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(4), ATM(8), BAX(1), CCND1(1), CCNE1(3), CDKN1A(2), E2F1(2), GADD45A(1), MDM2(2), RB1(12), TP53(144) | 4870970 | 180 | 148 | 132 | 5 | 16 | 50 | 19 | 38 | 57 | 0 | 5.7e-12 | <1.00e-15 | <4.40e-14
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 | ARF1(1), CCND1(1), CDKN1A(2), CDKN2A(26), CFL1(2), E2F1(2), MDM2(2), NXT1(1), PRB1(4), TP53(144) | 2299938 | 185 | 148 | 134 | 9 | 17 | 52 | 20 | 37 | 59 | 0 | 1.8e-11 | <1.00e-15 | <4.40e-14
7 | TELPATHWAY | Telomerase is a ribonucleotide protein that adds telomeric repeats to the 3' ends of chromosomes. | AKT1, BCL2, EGFR, G22P1, HSPCA, IGF1R, KRAS2, MYC, POLR2A, PPP2CA, PRKCA, RB1, TEP1, TERF1, TERT, TNKS, TP53, XRCC5 | 15 | AKT1(1), EGFR(7), IGF1R(1), MYC(1), POLR2A(2), PRKCA(5), RB1(12), TEP1(7), TERF1(3), TERT(3), TNKS(7), TP53(144), XRCC5(2) | 7526196 | 195 | 148 | 146 | 14 | 23 | 52 | 19 | 42 | 59 | 0 | 1.5e-09 | <1.00e-15 | <4.40e-14
8 | PLK3PATHWAY | Active Plk3 phosphorylates CDC25c, blocking the G2/M transition, and phosphorylates p53 to induce apoptosis. | ATM, ATR, CDC25C, CHEK1, CHEK2, CNK, TP53, YWHAH | 7 | ATM(8), ATR(13), CDC25C(1), CHEK1(5), CHEK2(3), TP53(144) | 4288732 | 174 | 146 | 126 | 6 | 17 | 48 | 21 | 37 | 51 | 0 | 1.8e-09 | <1.00e-15 | <4.40e-14
9 | 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(17), DAXX(3), HRAS(4), PAX3(4), RARA(1), RB1(12), SIRT1(1), SP100(3), TNF(1), TNFRSF1A(2), TNFRSF1B(1), TP53(144) | 5147404 | 193 | 146 | 145 | 14 | 16 | 55 | 22 | 42 | 58 | 0 | 8.9e-09 | <1.00e-15 | <4.40e-14
10 | 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(8), CDC25B(2), CDC25C(1), CHEK1(5), MYT1(4), RB1(12), TP53(144), WEE1(4) | 4718424 | 180 | 145 | 132 | 7 | 17 | 50 | 20 | 36 | 57 | 0 | 2.6e-10 | <1.00e-15 | <4.40e-14

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 | HSA00627_1,4_DICHLOROBENZENE_DEGRADATION | Genes involved in 1,4-dichlorobenzene degradation | CMBL | 1 | CMBL(3) | 134924 | 3 | 3 | 3 | 1 | 0 | 1 | 0 | 2 | 0 | 0 | 0.81 | 0.037 | 1
2 | HSA00902_MONOTERPENOID_BIOSYNTHESIS | Genes involved in monoterpenoid biosynthesis | CYP2C19, CYP2C9 | 2 | CYP2C19(8), CYP2C9(3) | 537026 | 11 | 10 | 11 | 3 | 5 | 3 | 0 | 2 | 1 | 0 | 0.55 | 0.17 | 1
3 | SA_G2_AND_M_PHASES | Cdc25 activates the cdc2/cyclin B complex to induce the G2/M transition. | CDC2, CDC25A, CDC25B, CDK7, CDKN1A, CHEK1, NEK1, WEE1 | 7 | CDC25B(2), CDK7(1), CDKN1A(2), CHEK1(5), NEK1(3), WEE1(4) | 1922578 | 17 | 17 | 17 | 1 | 7 | 5 | 1 | 3 | 1 | 0 | 0.1 | 0.25 | 1
4 | HSA00750_VITAMIN_B6_METABOLISM | Genes involved in vitamin B6 metabolism | AOX1, PDXK, PDXP, PNPO, PSAT1 | 5 | AOX1(13), PDXP(1), PSAT1(3) | 1297976 | 17 | 16 | 17 | 2 | 6 | 5 | 0 | 5 | 1 | 0 | 0.13 | 0.26 | 1
5 | HSA00472_D_ARGININE_AND_D_ORNITHINE_METABOLISM | Genes involved in D-arginine and D-ornithine metabolism | DAO | 1 | DAO(2) | 192952 | 2 | 2 | 2 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0.5 | 0.34 | 1
6 | HSA00550_PEPTIDOGLYCAN_BIOSYNTHESIS | Genes involved in peptidoglycan biosynthesis | GLUL, PGLYRP2 | 2 | GLUL(4), PGLYRP2(2) | 488788 | 6 | 5 | 6 | 0 | 1 | 4 | 1 | 0 | 0 | 0 | 0.15 | 0.36 | 1
7 | 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 | CCNE1(3), CUL1(4), E2F1(2), FBXW7(11), TFDP1(3) | 1763624 | 23 | 23 | 21 | 4 | 6 | 8 | 3 | 1 | 5 | 0 | 0.25 | 0.42 | 1
8 | 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 | 11 | CCNE1(3), CKS1B(1), CUL1(4), E2F1(2), RBX1(1), SKP2(2), TFDP1(3), UBE2M(1) | 1828772 | 17 | 16 | 17 | 1 | 5 | 8 | 0 | 2 | 2 | 0 | 0.05 | 0.43 | 1
9 | HSA00780_BIOTIN_METABOLISM | Genes involved in biotin metabolism | BTD, HLCS, SPCS1, SPCS3 | 4 | BTD(2), HLCS(5), SPCS1(1), SPCS3(2) | 826632 | 10 | 9 | 10 | 2 | 2 | 2 | 2 | 0 | 4 | 0 | 0.4 | 0.47 | 1
10 | IL18PATHWAY | Pro-inflammatory IL-18 is activated in macrophages by caspase-1 cleavage and, in conjunction with IL-12, stimulates Th1 cell differentiation. | CASP1, IFNG, IL12A, IL12B, IL18, IL2 | 6 | CASP1(1), IFNG(1), IL12A(1), IL12B(3) | 802958 | 6 | 6 | 6 | 1 | 3 | 1 | 0 | 0 | 2 | 0 | 0.52 | 0.52 | 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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