Lung Adenocarcinoma: 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: LUAD

- Number of patients in set: 229

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:LUAD.final_analysis_set.maf

- Significantly mutated genes (q ≤ 0.1): 188

- Mutations seen in COSMIC: 515

- Significantly mutated genes in COSMIC territory: 24

- Genes with clustered mutations (≤ 3 aa apart): 388

- Significantly mutated genesets: 16

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

Mutation Preprocessing

- Read 229 MAFs of type "Broad"

- Total number of mutations in input MAFs: 251233

- After removing 79 mutations outside chr1-24: 251154

- After removing 145352 noncoding mutations: 105802

- After collapsing adjacent/redundant mutations: 94321

Mutation Filtering

- Number of mutations before filtering: 94321

- After removing 1304 mutations outside gene set: 93017

- After removing 401 mutations outside category set: 92616

Results
Breakdown of Mutations by Type

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

type | count
--- | ---
Frame_Shift_Del | 1341
Frame_Shift_Ins | 558
In_Frame_Del | 200
In_Frame_Ins | 27
Missense_Mutation | 60650
Nonsense_Mutation | 4843
Nonstop_Mutation | 58
Silent | 22937
Splice_Site | 1868
Translation_Start_Site | 134
Total | 92616

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->A | 8889 | 379287204 | 0.000023 | 23 | 2.3 | 2.1
*Cp(A/C/T)->A | 22064 | 3108508517 | 7.1e-06 | 7.1 | 0.7 | 5
C->(T/G) | 19000 | 3487795721 | 5.4e-06 | 5.4 | 0.53 | 2.8
A->mut | 10782 | 3354933814 | 3.2e-06 | 3.2 | 0.32 | 3.9
indel+null | 8797 | 6842729535 | 1.3e-06 | 1.3 | 0.13 | NaN
double_null | 147 | 6842729535 | 2.1e-08 | 0.021 | 0.0021 | NaN
Total | 69679 | 6842729535 | 1e-05 | 10 | 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: LUAD.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->A

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

- n3 = number of nonsilent mutations of type: C->(T/G)

- 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: 188. 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 | KRTAP5-5 | keratin associated protein 5-5 | 155262 | 23 | 23 | 6 | 5 | 1 | 3 | 0 | 0 | 19 | 0 | 1.13e-14 | 0.99 | 2e-07 | 1 | 0.000032 | 0.000 | 0.000
2 | STK11 | serine/threonine kinase 11 | 199230 | 21 | 20 | 20 | 0 | 0 | 4 | 2 | 4 | 11 | 0 | 5.66e-15 | 0.01 | 0.00036 | 0.014 | 0.0003 | 1.11e-16 | 1.00e-12
3 | KEAP1 | kelch-like ECH-associated protein 1 | 418841 | 39 | 39 | 37 | 0 | 4 | 8 | 13 | 10 | 4 | 0 | 2.33e-15 | 0.000026 | 0.07 | 0.009 | 0.011 | 9.99e-16 | 1.81e-12
4 | TP53 | tumor protein p53 | 288082 | 126 | 117 | 104 | 2 | 8 | 22 | 31 | 18 | 47 | 0 | <1.00e-15 | 1.2e-10 | 2e-07 | 2e-07 | 0 | <1.00e-15 | <1.81e-12
5 | KRAS | v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog | 161903 | 60 | 60 | 6 | 0 | 0 | 47 | 10 | 3 | 0 | 0 | <1.00e-15 | 0.002 | 2e-07 | 2e-07 | 0 | <1.00e-15 | <1.81e-12
6 | EGFR | epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian) | 918061 | 33 | 27 | 19 | 7 | 2 | 5 | 4 | 13 | 9 | 0 | 0.00167 | 0.65 | 2e-07 | 0.0012 | 0 | <1.00e-15 | <1.81e-12
7 | ASTN2 | astrotactin 2 | 839056 | 29 | 23 | 29 | 7 | 4 | 12 | 5 | 4 | 4 | 0 | 0.380 | 0.31 | 6e-07 | 0.00035 | 0 | <1.00e-15 | <1.81e-12
8 | CDKN2A | cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) | 226023 | 14 | 14 | 14 | 1 | 0 | 1 | 4 | 4 | 5 | 0 | 5.10e-09 | 0.26 | 0.000016 | 4e-07 | 0 | <1.00e-15 | <1.81e-12
9 | OR6C4 | olfactory receptor, family 6, subfamily C, member 4 | 213428 | 3 | 3 | 3 | 1 | 0 | 0 | 2 | 0 | 1 | 0 | 0.146 | 0.64 | 0.0029 | 0.00057 | 0 | <1.00e-15 | <1.81e-12
10 | ROPN1 | ropporin, rhophilin associated protein 1 | 139461 | 3 | 3 | 3 | 0 | 1 | 0 | 2 | 0 | 0 | 0 | 0.217 | 0.29 | 0.089 | 0.0091 | 0 | <1.00e-15 | <1.81e-12
11 | NAV3 | neuron navigator 3 | 1659792 | 66 | 52 | 66 | 4 | 4 | 36 | 16 | 6 | 3 | 1 | 1.07e-13 | 0.0026 | 0.32 | 0.48 | 0.4 | 1.37e-12 | 2.25e-09
12 | MAGEC1 | melanoma antigen family C, 1 | 774020 | 40 | 34 | 39 | 2 | 2 | 14 | 13 | 7 | 4 | 0 | 1.30e-13 | 0.0051 | 0.69 | 0.38 | 0.67 | 2.72e-12 | 4.10e-09
13 | CDH10 | cadherin 10, type 2 (T2-cadherin) | 552119 | 51 | 40 | 51 | 8 | 4 | 27 | 12 | 1 | 7 | 0 | 2.21e-11 | 0.27 | 0.82 | 0.44 | 0.77 | 4.42e-10 | 5.92e-07
14 | TMTC1 | transmembrane and tetratricopeptide repeat containing 1 | 543417 | 32 | 26 | 30 | 3 | 3 | 17 | 7 | 3 | 2 | 0 | 4.81e-11 | 0.055 | 0.92 | 0.1 | 0.37 | 4.58e-10 | 5.92e-07
15 | MUC7 | mucin 7, secreted | 261518 | 19 | 17 | 19 | 1 | 0 | 8 | 3 | 5 | 3 | 0 | 2.86e-10 | 0.091 | 0.04 | 0.53 | 0.08 | 5.79e-10 | 6.99e-07
16 | EPHA6 | EPH receptor A6 | 755242 | 33 | 30 | 33 | 4 | 3 | 17 | 7 | 3 | 3 | 0 | 7.58e-09 | 0.17 | 0.11 | 0.0023 | 0.004 | 7.70e-10 | 8.70e-07
17 | ZNF676 | zinc finger protein 676 | 407391 | 22 | 21 | 21 | 2 | 0 | 10 | 9 | 0 | 3 | 0 | 6.20e-09 | 0.25 | 0.0039 | 0.23 | 0.007 | 1.08e-09 | 1.15e-06
18 | OR4C16 | olfactory receptor, family 4, subfamily C, member 16 | 214115 | 15 | 14 | 14 | 0 | 0 | 9 | 2 | 3 | 1 | 0 | 1.57e-08 | 0.035 | 0.0019 | 0.17 | 0.0034 | 1.33e-09 | 1.33e-06
19 | RIMS2 | regulating synaptic membrane exocytosis 2 | 994318 | 45 | 39 | 45 | 4 | 4 | 16 | 10 | 8 | 7 | 0 | 2.99e-09 | 0.051 | 0.14 | 0.14 | 0.095 | 6.55e-09 | 6.23e-06
20 | GABRB3 | gamma-aminobutyric acid (GABA) A receptor, beta 3 | 314646 | 18 | 17 | 18 | 1 | 3 | 6 | 4 | 4 | 1 | 0 | 1.66e-08 | 0.038 | 0.015 | 0.39 | 0.028 | 1.05e-08 | 9.49e-06
21 | OR2L3 | olfactory receptor, family 2, subfamily L, member 3 | 215947 | 16 | 15 | 16 | 2 | 1 | 9 | 2 | 4 | 0 | 0 | 1.81e-09 | 0.19 | 0.34 | 0.68 | 0.59 | 2.30e-08 | 1.98e-05
22 | CD5L | CD5 molecule-like | 244572 | 15 | 15 | 15 | 1 | 3 | 3 | 0 | 5 | 4 | 0 | 1.22e-08 | 0.1 | 0.25 | 0.066 | 0.11 | 2.86e-08 | 2.24e-05
23 | CNBD1 | cyclic nucleotide binding domain containing 1 | 238160 | 14 | 14 | 14 | 1 | 0 | 5 | 3 | 4 | 2 | 0 | 7.99e-09 | 0.32 | 0.4 | 0.056 | 0.17 | 2.96e-08 | 2.24e-05
24 | ELTD1 | EGF, latrophilin and seven transmembrane domain containing 1 | 482503 | 20 | 20 | 20 | 0 | 0 | 4 | 4 | 8 | 4 | 0 | 1.39e-09 | 0.015 | 0.61 | 0.54 | 1 | 2.98e-08 | 2.24e-05
25 | KRTAP1-5 | keratin associated protein 1-5 | 121141 | 7 | 7 | 2 | 1 | 0 | 0 | 0 | 6 | 1 | 0 | 3.20e-06 | 0.64 | 0.000099 | 0.98 | 0.00048 | 3.30e-08 | 2.39e-05
26 | TRIM58 | tripartite motif-containing 58 | 254648 | 15 | 15 | 15 | 2 | 1 | 3 | 3 | 5 | 3 | 0 | 5.51e-08 | 0.19 | 0.029 | 0.18 | 0.034 | 3.94e-08 | 2.68e-05
27 | OR2T4 | olfactory receptor, family 2, subfamily T, member 4 | 240679 | 18 | 17 | 18 | 2 | 1 | 7 | 8 | 2 | 0 | 0 | 1.02e-08 | 0.071 | 0.12 | 0.87 | 0.19 | 4.10e-08 | 2.68e-05
28 | REG3A | regenerating islet-derived 3 alpha | 125492 | 15 | 14 | 14 | 2 | 0 | 4 | 7 | 2 | 2 | 0 | 4.10e-09 | 0.25 | 0.31 | 0.54 | 0.48 | 4.14e-08 | 2.68e-05
29 | BRAF | v-raf murine sarcoma viral oncogene homolog B1 | 510899 | 17 | 17 | 12 | 1 | 1 | 7 | 2 | 5 | 2 | 0 | 5.99e-07 | 0.096 | 0.0088 | 0.16 | 0.018 | 2.10e-07 | 0.000131
30 | OR4A5 | olfactory receptor, family 4, subfamily A, member 5 | 218008 | 13 | 12 | 13 | 0 | 1 | 4 | 3 | 4 | 1 | 0 | 3.67e-08 | 0.035 | 0.27 | 0.63 | 0.42 | 2.92e-07 | 0.000171
31 | NRAS | neuroblastoma RAS viral (v-ras) oncogene homolog | 134194 | 4 | 4 | 2 | 1 | 0 | 1 | 0 | 3 | 0 | 0 | 0.0161 | 0.71 | 4e-07 | 0.19 | 1e-06 | 3.04e-07 | 0.000171
32 | SPRR3 | small proline-rich protein 3 | 117706 | 7 | 7 | 4 | 0 | 0 | 1 | 0 | 1 | 5 | 0 | 1.29e-05 | 0.62 | 0.0024 | 0.046 | 0.0013 | 3.07e-07 | 0.000171
33 | REG1B | regenerating islet-derived 1 beta (pancreatic stone protein, pancreatic thread protein) | 119309 | 14 | 13 | 14 | 2 | 1 | 7 | 1 | 3 | 2 | 0 | 1.47e-07 | 0.39 | 0.5 | 0.04 | 0.11 | 3.12e-07 | 0.000171
34 | BAGE2 | B melanoma antigen family, member 2 | 79234 | 9 | 9 | 9 | 0 | 0 | 4 | 2 | 1 | 2 | 0 | 2.11e-08 | 0.12 | 0.86 | 0.44 | 0.88 | 3.49e-07 | 0.000186
35 | OR2L8 | olfactory receptor, family 2, subfamily L, member 8 | 215947 | 15 | 13 | 13 | 2 | 1 | 8 | 3 | 2 | 1 | 0 | 3.08e-07 | 0.23 | 0.072 | 0.19 | 0.094 | 5.34e-07 | 0.000276

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: 24. Number of genes displayed: 10

rank | gene | description | n | cos | n_cos | N_cos | cos_ev | p | q
--- | --- | --- | --- | --- | --- | --- | --- | --- | ---
1 | LRP1B | low density lipoprotein-related protein 1B (deleted in tumors) | 149 | 18 | 8 | 4122 | 8 | 3.9e-14 | 1.8e-10
2 | KRAS | v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog | 60 | 51 | 60 | 11679 | 797017 | 1e-13 | 2.3e-10
3 | BRAF | v-raf murine sarcoma viral oncogene homolog B1 | 17 | 88 | 12 | 20152 | 21212 | 1.6e-13 | 2.4e-10
4 | STK11 | serine/threonine kinase 11 | 21 | 130 | 14 | 29770 | 27 | 2.2e-13 | 2.5e-10
5 | EGFR | epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian) | 33 | 218 | 29 | 49922 | 10294 | 3e-13 | 2.6e-10
6 | TP53 | tumor protein p53 | 126 | 308 | 121 | 70532 | 18205 | 3.4e-13 | 2.6e-10
7 | CDKN2A | cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) | 14 | 315 | 14 | 72135 | 259 | 4.2e-13 | 2.7e-10
8 | MET | met proto-oncogene (hepatocyte growth factor receptor) | 12 | 33 | 6 | 7557 | 64 | 2.7e-10 | 1.5e-07
9 | PIK3CA | phosphoinositide-3-kinase, catalytic, alpha polypeptide | 11 | 184 | 9 | 42136 | 3946 | 9.2e-10 | 4.6e-07
10 | NF1 | neurofibromin 1 (neurofibromatosis, von Recklinghausen disease, Watson disease) | 29 | 285 | 9 | 65265 | 13 | 3.8e-08 | 0.000017

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
--- | --- | --- | --- | --- | --- | --- | --- | --- | --- | ---
6688 | KRAS | v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog | 60 | 0 | 1382 | 1488 | 1488 | 1382 | 1488 | 1488
13091 | TP53 | tumor protein p53 | 126 | 0 | 53 | 200 | 636 | 53 | 200 | 636
3862 | EGFR | epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian) | 33 | 0 | 39 | 60 | 60 | 39 | 60 | 60
6750 | KRTAP1-5 | keratin associated protein 1-5 | 7 | 0 | 15 | 15 | 15 | 15 | 15 | 15
9561 | PIK3CA | phosphoinositide-3-kinase, catalytic, alpha polypeptide | 11 | 0 | 6 | 10 | 11 | 6 | 10 | 11
8465 | NRAS | neuroblastoma RAS viral (v-ras) oncogene homolog | 4 | 0 | 6 | 6 | 6 | 6 | 6 | 6
13295 | TSHZ3 | teashirt zinc finger homeobox 3 | 39 | 0 | 5 | 14 | 29 | 5 | 14 | 29
1224 | BRAF | v-raf murine sarcoma viral oncogene homolog B1 | 17 | 0 | 5 | 9 | 13 | 5 | 9 | 13
6426 | KEAP1 | kelch-like ECH-associated protein 1 | 39 | 0 | 4 | 17 | 44 | 4 | 17 | 44
14412 | ZNF536 | zinc finger protein 536 | 54 | 0 | 4 | 11 | 28 | 4 | 11 | 28

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: 16. 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 | 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(22), ATR(17), CDC25C(3), CHEK1(6), CHEK2(2), TP53(126) | 5517526 | 176 | 134 | 153 | 7 | 10 | 35 | 48 | 28 | 55 | 0 | 1e-08 | 2e-15 | 3.8e-13
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 | HDAC1(3), MAX(3), SP1(1), SP3(4), TP53(126), WT1(8) | 2427858 | 145 | 120 | 123 | 10 | 9 | 29 | 35 | 21 | 51 | 0 | 1.2e-06 | 3.4e-15 | 3.8e-13
3 | 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 | CHUK(3), DNAJC3(3), MAP3K14(1), NFKB1(3), NFKBIA(1), TP53(126) | 3372941 | 137 | 119 | 115 | 9 | 9 | 23 | 36 | 18 | 51 | 0 | 2.2e-06 | 3.8e-15 | 3.8e-13
4 | 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(2), CDKN2A(14), E2F1(3), MDM2(2), PIK3CA(11), PIK3R1(3), POLR1A(8), POLR1B(10), POLR1D(2), RB1(13), TBX2(1), TP53(126), TWIST1(1) | 7038773 | 196 | 131 | 170 | 15 | 16 | 33 | 53 | 29 | 65 | 0 | 2.8e-08 | 4.7e-15 | 3.8e-13
5 | 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(4), DAXX(6), HRAS(1), PAX3(6), PML(7), RARA(3), RB1(13), SIRT1(1), SP100(9), TNFRSF1B(1), TP53(126) | 6622222 | 177 | 129 | 155 | 15 | 14 | 30 | 47 | 25 | 61 | 0 | 3.8e-07 | 4.9e-15 | 3.8e-13
6 | 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(8), ATM(22), BAX(1), BCL2(1), CCND1(2), CCNE1(3), CDK2(4), CDK4(2), CDKN1A(1), E2F1(3), GADD45A(1), MDM2(2), PCNA(1), RB1(13), TP53(126) | 6266585 | 190 | 141 | 167 | 16 | 16 | 37 | 42 | 29 | 66 | 0 | 1.9e-06 | 5.1e-15 | 3.8e-13
7 | 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(20), ATM(22), BAX(1), CDKN1A(1), CPB2(4), CSNK1A1(1), CSNK1D(2), GADD45A(1), HIF1A(1), IGFBP3(2), MAPK8(3), MDM2(2), NQO1(3), TP53(126) | 7172280 | 189 | 136 | 165 | 18 | 17 | 40 | 45 | 27 | 60 | 0 | 0.000012 | 5.3e-15 | 3.8e-13
8 | 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 | IFNG(4), IFNGR1(3), IFNGR2(3), IKBKB(3), JAK2(4), LIN7A(2), NFKB1(3), NFKBIA(1), RB1(13), TNFRSF1B(1), TP53(126), USH1C(4), WT1(8) | 6332308 | 175 | 131 | 153 | 16 | 15 | 35 | 41 | 21 | 63 | 0 | 1.8e-06 | 5.8e-15 | 3.8e-13
9 | 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 | ARF3(1), CCND1(2), CDK2(4), CDK4(2), CDKN1A(1), CDKN1B(3), CDKN2A(14), E2F1(3), MDM2(2), NXT1(1), PRB1(3), TP53(126) | 2958909 | 162 | 124 | 140 | 8 | 15 | 29 | 38 | 24 | 56 | 0 | 1.1e-09 | 6e-15 | 3.8e-13
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(22), CDC25A(4), CDC25B(1), CDC25C(3), CDK2(4), CDK4(2), CHEK1(6), MYT1(6), RB1(13), TP53(126), WEE1(3) | 6070332 | 190 | 138 | 167 | 13 | 15 | 37 | 43 | 29 | 66 | 0 | 1.6e-07 | 6.2e-15 | 3.8e-13

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 | 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 | CCNE1(3), CDC34(1), CDK2(4), CUL1(6), E2F1(3), FBXW7(4), RB1(13), TFDP1(3) | 2895018 | 37 | 30 | 37 | 3 | 5 | 8 | 9 | 6 | 9 | 0 | 0.023 | 0.063 | 1
2 | 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 | CCNE1(3), CDK2(4), CDKN1B(3), CUL1(6), E2F1(3), NEDD8(2), RB1(13), SKP2(4), TFDP1(3), UBE2M(1) | 2978832 | 42 | 33 | 42 | 5 | 5 | 8 | 11 | 7 | 11 | 0 | 0.051 | 0.11 | 1
3 | 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(2), IFNG(4), IL12A(3), IL2(5) | 1033019 | 14 | 12 | 13 | 1 | 2 | 7 | 2 | 2 | 1 | 0 | 0.15 | 0.23 | 1
4 | HSA00130_UBIQUINONE_BIOSYNTHESIS | Genes involved in ubiquinone biosynthesis | COQ2, COQ3, COQ5, COQ6, COQ7, ND1, ND2, ND3, ND4, ND4L, ND5, ND6, NDUFA12, NDUFA13, NDUFB11 | 8 | COQ3(4), COQ5(5), COQ6(3), COQ7(1), NDUFA12(2), NDUFA13(4), NDUFB11(1) | 1380412 | 20 | 14 | 20 | 2 | 5 | 5 | 5 | 1 | 4 | 0 | 0.082 | 0.31 | 1
5 | BOTULINPATHWAY | Blockade of Neurotransmitter Relase by Botulinum Toxin | CHRM1, CHRNA1, SNAP25, STX1A, VAMP2 | 5 | CHRM1(2), CHRNA1(7), SNAP25(4), STX1A(3) | 1118665 | 16 | 13 | 16 | 3 | 5 | 3 | 5 | 1 | 2 | 0 | 0.2 | 0.35 | 1
6 | HSA00902_MONOTERPENOID_BIOSYNTHESIS | Genes involved in monoterpenoid biosynthesis | CYP2C19, CYP2C9 | 2 | CYP2C19(9), CYP2C9(3) | 690893 | 12 | 11 | 12 | 3 | 2 | 3 | 3 | 2 | 2 | 0 | 0.54 | 0.4 | 1
7 | 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 | CCNA1(2), CCNE1(3), CDC34(1), CDK2(4), CUL1(6), E2F1(3), RB1(13), SKP2(4), TFDP1(3) | 2974481 | 39 | 31 | 39 | 6 | 6 | 9 | 9 | 6 | 9 | 0 | 0.12 | 0.42 | 1
8 | HSA00730_THIAMINE_METABOLISM | Genes involved in thiamine metabolism | LHPP, MTMR1, MTMR2, MTMR6, NFS1, PHPT1, THTPA, TPK1 | 8 | LHPP(2), MTMR1(5), MTMR2(2), MTMR6(6), NFS1(4), PHPT1(1), TPK1(5) | 2218323 | 25 | 20 | 25 | 3 | 1 | 9 | 6 | 7 | 1 | 1 | 0.15 | 0.54 | 1
9 | HSA00031_INOSITOL_METABOLISM | Genes involved in inositol metabolism | ALDH6A1, TPI1 | 2 | TPI1(6) | 566088 | 6 | 5 | 6 | 0 | 0 | 3 | 2 | 1 | 0 | 0 | 0.24 | 0.6 | 1
10 | INOSITOL_METABOLISM |  | ALDH6A1, ALDOA, ALDOB, ALDOC, TPI1 | 5 | ALDOA(2), ALDOB(4), ALDOC(1), TPI1(6) | 1340337 | 13 | 10 | 13 | 0 | 0 | 5 | 4 | 2 | 2 | 0 | 0.043 | 0.72 | 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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