Brain Lower Grade Glioma: Mutation Analysis (MutSig v2.0)
(primary solid tumor cohort)
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: LGG-TP

- Number of patients in set: 170

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:LGG-TP.final_analysis_set.maf

- Significantly mutated genes (q ≤ 0.1): 29

- Mutations seen in COSMIC: 331

- Significantly mutated genes in COSMIC territory: 12

- Genes with clustered mutations (≤ 3 aa apart): 143

- Significantly mutated genesets: 95

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

Mutation Preprocessing

- Read 170 MAFs of type "Broad"

- Total number of mutations in input MAFs: 24649

- After removing 12 mutations outside chr1-24: 24637

- After removing 468 blacklisted mutations: 24169

- After removing 446 noncoding mutations: 23723

Mutation Filtering

- Number of mutations before filtering: 23723

- After removing 302 mutations outside gene set: 23421

- After removing 96 mutations outside category set: 23325

- After removing 3 "impossible" mutations in

- gene-patient-category bins of zero coverage: 22924

Results
Breakdown of Mutations by Type

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

type | count
--- | ---
Frame_Shift_Del | 441
Frame_Shift_Ins | 246
In_Frame_Del | 226
In_Frame_Ins | 10
Missense_Mutation | 15136
Nonsense_Mutation | 938
Nonstop_Mutation | 12
Silent | 5859
Splice_Site | 416
Translation_Start_Site | 41
Total | 23325

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 | 4768 | 274694298 | 0.000017 | 17 | 5 | 2.1
*Cp(A/C/T)->T | 3404 | 2262327426 | 1.5e-06 | 1.5 | 0.43 | 1.7
A->G | 2059 | 2444442244 | 8.4e-07 | 0.84 | 0.24 | 2.3
transver | 4945 | 4981463968 | 9.9e-07 | 0.99 | 0.28 | 5
indel+null | 2204 | 4981463968 | 4.4e-07 | 0.44 | 0.13 | NaN
double_null | 84 | 4981463968 | 1.7e-08 | 0.017 | 0.0048 | NaN
Total | 17464 | 4981463968 | 3.5e-06 | 3.5 | 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: LGG-TP.patients.counts_and_rates.txt

CoMut Plot

Figure 3. Get High-res Image The matrix in the center of the figure represents individual mutations in patient samples, color-coded by type of mutation, for the significantly mutated genes. The rate of synonymous and non-synonymous mutations is displayed at the top of the matrix. The barplot on the left of the matrix shows the number of mutations in each gene. The percentages represent the fraction of tumors with at least one mutation in the specified gene. The barplot to the right of the matrix displays the q-values for the most significantly mutated genes. The purple boxplots below the matrix (only displayed if required columns are present in the provided MAF) represent the distributions of allelic fractions observed in each sample. The plot at the bottom represents the base substitution distribution of individual samples, using the same categories that were used to calculate significance.

Significantly Mutated Genes

Column Descriptions:

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

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

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

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

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

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

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

- n3 = number of nonsilent mutations of type: A->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: 29. 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_cons | p_joint | p | q
--- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | ---
1 | IDH1 | isocitrate dehydrogenase 1 (NADP+), soluble | 216008 | 131 | 131 | 2 | 0 | 123 | 0 | 0 | 8 | 0 | 0 | <1.00e-15 | 1.6e-15 | 1 | 0 | <1.00e-15 | <6.03e-12
2 | TP53 | tumor protein p53 | 209503 | 113 | 88 | 63 | 2 | 46 | 12 | 14 | 25 | 13 | 3 | 2.11e-15 | 1.1e-11 | 0 | 0 | <1.00e-15 | <6.03e-12
3 | IDH2 | isocitrate dehydrogenase 2 (NADP+), mitochondrial | 198137 | 6 | 6 | 2 | 0 | 0 | 4 | 0 | 2 | 0 | 0 | 6.51e-08 | 0.058 | 0.98 | 0 | <1.00e-15 | <6.03e-12
4 | PIK3CA | phosphoinositide-3-kinase, catalytic, alpha polypeptide | 558011 | 15 | 15 | 10 | 0 | 0 | 5 | 5 | 2 | 3 | 0 | 4.11e-15 | 0.014 | 0.0019 | 0.012 | 1.89e-15 | 8.53e-12
5 | ATRX | alpha thalassemia/mental retardation syndrome X-linked (RAD54 homolog, S. cerevisiae) | 1280217 | 78 | 73 | 70 | 2 | 2 | 3 | 6 | 6 | 58 | 3 | 2.33e-15 | 0.0024 | 0.44 | 0.21 | 1.78e-14 | 6.43e-11
6 | CIC | capicua homolog (Drosophila) | 702843 | 40 | 35 | 34 | 0 | 15 | 1 | 1 | 5 | 18 | 0 | 6.99e-15 | 0.00012 | 0.86 | 0.23 | 5.72e-14 | 1.72e-10
7 | FUBP1 | far upstream element (FUSE) binding protein 1 | 335021 | 19 | 19 | 18 | 2 | 0 | 0 | 1 | 2 | 16 | 0 | 9.88e-15 | 0.66 | 0.84 | 0.26 | 8.97e-14 | 2.32e-10
8 | PIK3R1 | phosphoinositide-3-kinase, regulatory subunit 1 (alpha) | 401699 | 13 | 12 | 11 | 1 | 1 | 2 | 3 | 0 | 7 | 0 | 1.29e-13 | 0.26 | 0.87 | 0.061 | 2.62e-13 | 5.92e-10
9 | NOTCH1 | Notch homolog 1, translocation-associated (Drosophila) | 1034775 | 23 | 16 | 20 | 2 | 4 | 3 | 1 | 6 | 7 | 2 | 1.58e-10 | 0.029 | 0.02 | 0.00015 | 7.58e-13 | 1.52e-09
10 | ZNF844 | zinc finger protein 844 | 212375 | 6 | 5 | 2 | 0 | 0 | 0 | 2 | 4 | 0 | 0 | 1.02e-06 | 0.23 | 0.98 | 0.000013 | 3.35e-10 | 6.06e-07
11 | IL32 | interleukin 32 | 87796 | 4 | 4 | 1 | 0 | 0 | 0 | 0 | 0 | 4 | 0 | 1.28e-06 | 1 | 0.95 | 0.000026 | 8.51e-10 | 1.40e-06
12 | PTEN | phosphatase and tensin homolog (mutated in multiple advanced cancers 1) | 206544 | 8 | 8 | 8 | 0 | 1 | 1 | 0 | 3 | 3 | 0 | 2.93e-10 | 0.25 | 0.24 | 0.36 | 2.54e-09 | 3.83e-06
13 | TIMD4 | T-cell immunoglobulin and mucin domain containing 4 | 199368 | 6 | 6 | 3 | 1 | 0 | 1 | 0 | 1 | 4 | 0 | 4.11e-08 | 0.82 | 0.58 | 0.012 | 1.07e-08 | 1.49e-05
14 | CREBZF | CREB/ATF bZIP transcription factor | 174308 | 4 | 4 | 1 | 0 | 0 | 0 | 0 | 0 | 4 | 0 | 0.000269 | 1 | 0.32 | 4e-06 | 2.33e-08 | 3.01e-05
15 | ZNF57 | zinc finger protein 57 | 284991 | 7 | 6 | 4 | 0 | 1 | 1 | 1 | 4 | 0 | 0 | 8.97e-06 | 0.16 | 1 | 0.00014 | 2.72e-08 | 3.28e-05
16 | NF1 | neurofibromin 1 (neurofibromatosis, von Recklinghausen disease, Watson disease) | 1473142 | 14 | 11 | 14 | 1 | 1 | 2 | 1 | 2 | 3 | 5 | 5.76e-08 | 0.096 | 0.92 | 0.58 | 6.05e-07 | 0.000649
17 | ARID1A | AT rich interactive domain 1A (SWI-like) | 986587 | 13 | 11 | 13 | 0 | 1 | 0 | 0 | 1 | 10 | 1 | 3.35e-08 | 0.077 | 0.51 | 1 | 6.10e-07 | 0.000649
18 | TCF12 | transcription factor 12 (HTF4, helix-loop-helix transcription factors 4) | 385695 | 6 | 6 | 5 | 0 | 0 | 0 | 0 | 0 | 6 | 0 | 1.83e-06 | 0.75 | 0.11 | 0.27 | 7.58e-06 | 0.00762
19 | NOX4 | NADPH oxidase 4 | 305569 | 6 | 5 | 3 | 0 | 0 | 1 | 1 | 0 | 4 | 0 | 9.77e-05 | 0.45 | 0.54 | 0.0064 | 9.59e-06 | 0.00913
20 | EGFR | epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian) | 669290 | 10 | 8 | 8 | 0 | 1 | 2 | 0 | 6 | 1 | 0 | 2.15e-05 | 0.08 | 0.11 | 0.049 | 1.57e-05 | 0.0142
21 | ZBTB20 | zinc finger and BTB domain containing 20 | 345917 | 7 | 7 | 7 | 1 | 1 | 0 | 3 | 1 | 2 | 0 | 1.92e-06 | 0.5 | 0.46 | 0.59 | 1.67e-05 | 0.0144
22 | MUC7 | mucin 7, secreted | 194133 | 8 | 5 | 7 | 0 | 1 | 2 | 5 | 0 | 0 | 0 | 4.66e-06 | 0.018 | 0.49 | 0.35 | 2.35e-05 | 0.0193
23 | ZNF845 | zinc finger protein 845 | 472789 | 6 | 6 | 4 | 1 | 0 | 3 | 2 | 1 | 0 | 0 | 3.85e-05 | 0.32 | 0.99 | 0.055 | 2.99e-05 | 0.0235
24 | ANKRD30A | ankyrin repeat domain 30A | 634412 | 7 | 7 | 5 | 2 | 2 | 0 | 0 | 5 | 0 | 0 | 2.92e-05 | 0.56 | 0.75 | 0.14 | 5.37e-05 | 0.0405
25 | SPDYE5 | speedy homolog E5 (Xenopus laevis) | 144980 | 4 | 4 | 3 | 0 | 3 | 0 | 1 | 0 | 0 | 0 | 4.19e-05 | 0.38 | 0.72 | 0.12 | 6.69e-05 | 0.0484
26 | SCAF1 | SR-related CTD-associated factor 1 | 327357 | 4 | 4 | 2 | 0 | 1 | 0 | 0 | 0 | 3 | 0 | 0.00199 | 0.68 | 0.18 | 0.0028 | 7.32e-05 | 0.0509
27 | PRDM9 | PR domain containing 9 | 462689 | 6 | 5 | 6 | 1 | 2 | 1 | 1 | 2 | 0 | 0 | 0.000207 | 0.49 | 0.12 | 0.039 | 0.000102 | 0.0680
28 | PRAMEF11 | PRAME family member 11 | 208592 | 6 | 5 | 6 | 1 | 0 | 2 | 2 | 2 | 0 | 0 | 2.55e-05 | 0.4 | 0.79 | 0.46 | 0.000144 | 0.0924
29 | ZCCHC12 | zinc finger, CCHC domain containing 12 | 206206 | 3 | 3 | 1 | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 0.00208 | 0.41 | 0.74 | 0.0058 | 0.000148 | 0.0924
30 | ZNF91 | zinc finger protein 91 | 598251 | 5 | 5 | 4 | 1 | 2 | 1 | 2 | 0 | 0 | 0 | 3.15e-05 | 0.4 | 0.43 | 0.52 | 0.000195 | 0.118
31 | C3orf35 | chromosome 3 open reading frame 35 | 86114 | 3 | 3 | 3 | 0 | 0 | 0 | 2 | 0 | 1 | 0 | 0.000254 | 0.27 | 0.046 | 0.092 | 0.000273 | 0.159
32 | RPTN | repetin | 401710 | 6 | 5 | 6 | 1 | 2 | 1 | 0 | 1 | 2 | 0 | 0.000168 | 0.58 | 0.43 | 0.16 | 0.000309 | 0.175
33 | DDX5 | DEAD (Asp-Glu-Ala-Asp) box polypeptide 5 | 320234 | 5 | 5 | 4 | 0 | 0 | 2 | 0 | 1 | 2 | 0 | 0.000103 | 0.46 | 0.3 | 0.3 | 0.000356 | 0.195
34 | PSD3 | pleckstrin and Sec7 domain containing 3 | 548440 | 6 | 6 | 6 | 0 | 0 | 1 | 4 | 0 | 1 | 0 | 0.000118 | 0.1 | 0.62 | 0.32 | 0.000418 | 0.222
35 | EIF1AX | eukaryotic translation initiation factor 1A, X-linked | 75006 | 2 | 2 | 2 | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 0.00232 | 0.71 | 0.35 | 0.017 | 0.000434 | 0.224

IDH1

Figure S1. This figure depicts the distribution of mutations and mutation types across the IDH1 significant gene.

TP53

Figure S2. This figure depicts the distribution of mutations and mutation types across the TP53 significant gene.

IDH2

Figure S3. This figure depicts the distribution of mutations and mutation types across the IDH2 significant gene.

PIK3CA

Figure S4. This figure depicts the distribution of mutations and mutation types across the PIK3CA significant gene.

ATRX

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

CIC

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

FUBP1

Figure S7. This figure depicts the distribution of mutations and mutation types across the FUBP1 significant gene.

PIK3R1

Figure S8. This figure depicts the distribution of mutations and mutation types across the PIK3R1 significant gene.

NOTCH1

Figure S9. This figure depicts the distribution of mutations and mutation types across the NOTCH1 significant gene.

ZNF844

Figure S10. This figure depicts the distribution of mutations and mutation types across the ZNF844 significant gene.

IL32

Figure S11. This figure depicts the distribution of mutations and mutation types across the IL32 significant gene.

PTEN

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

TIMD4

Figure S13. This figure depicts the distribution of mutations and mutation types across the TIMD4 significant gene.

CREBZF

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

ZNF57

Figure S15. This figure depicts the distribution of mutations and mutation types across the ZNF57 significant gene.

NF1

Figure S16. This figure depicts the distribution of mutations and mutation types across the NF1 significant gene.

ARID1A

Figure S17. This figure depicts the distribution of mutations and mutation types across the ARID1A significant gene.

TCF12

Figure S18. This figure depicts the distribution of mutations and mutation types across the TCF12 significant gene.

NOX4

Figure S19. This figure depicts the distribution of mutations and mutation types across the NOX4 significant gene.

EGFR

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

ZBTB20

Figure S21. This figure depicts the distribution of mutations and mutation types across the ZBTB20 significant gene.

MUC7

Figure S22. This figure depicts the distribution of mutations and mutation types across the MUC7 significant gene.

ZNF845

Figure S23. This figure depicts the distribution of mutations and mutation types across the ZNF845 significant gene.

ANKRD30A

Figure S24. This figure depicts the distribution of mutations and mutation types across the ANKRD30A significant gene.

SPDYE5

Figure S25. This figure depicts the distribution of mutations and mutation types across the SPDYE5 significant gene.

SCAF1

Figure S26. This figure depicts the distribution of mutations and mutation types across the SCAF1 significant gene.

PRDM9

Figure S27. This figure depicts the distribution of mutations and mutation types across the PRDM9 significant gene.

PRAMEF11

Figure S28. This figure depicts the distribution of mutations and mutation types across the PRAMEF11 significant gene.

ZCCHC12

Figure S29. This figure depicts the distribution of mutations and mutation types across the ZCCHC12 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: 12. Number of genes displayed: 10

rank | gene | description | n | cos | n_cos | N_cos | cos_ev | p | q
--- | --- | --- | --- | --- | --- | --- | --- | --- | ---
1 | IDH1 | isocitrate dehydrogenase 1 (NADP+), soluble | 131 | 5 | 131 | 850 | 195452 | 3.1e-14 | 8.4e-11
2 | IDH2 | isocitrate dehydrogenase 2 (NADP+), mitochondrial | 6 | 6 | 6 | 1020 | 498 | 3.7e-14 | 8.4e-11
3 | PIK3R1 | phosphoinositide-3-kinase, regulatory subunit 1 (alpha) | 13 | 33 | 6 | 5610 | 12 | 2.8e-13 | 4.2e-10
4 | PIK3CA | phosphoinositide-3-kinase, catalytic, alpha polypeptide | 15 | 220 | 13 | 37400 | 1923 | 1.2e-12 | 1.4e-09
5 | TP53 | tumor protein p53 | 113 | 356 | 111 | 60520 | 42165 | 1.8e-12 | 1.6e-09
6 | PTEN | phosphatase and tensin homolog (mutated in multiple advanced cancers 1) | 8 | 767 | 8 | 130390 | 503 | 3.2e-08 | 0.000022
7 | EGFR | epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian) | 10 | 293 | 6 | 49810 | 59 | 3.4e-08 | 0.000022
8 | SMARCA4 | SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4 | 10 | 30 | 3 | 5100 | 1 | 9.4e-07 | 0.00047
9 | NF1 | neurofibromin 1 (neurofibromatosis, von Recklinghausen disease, Watson disease) | 14 | 285 | 5 | 48450 | 7 | 1e-06 | 0.00047
10 | PTPN11 | protein tyrosine phosphatase, non-receptor type 11 (Noonan syndrome 1) | 4 | 32 | 3 | 5440 | 60 | 1.1e-06 | 0.00047

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
--- | --- | --- | --- | --- | --- | --- | --- | --- | --- | ---
3644 | IDH1 | isocitrate dehydrogenase 1 (NADP+), soluble | 131 | 0 | 8515 | 8515 | 8515 | 8515 | 8515 | 8515
8202 | TP53 | tumor protein p53 | 113 | 0 | 476 | 660 | 1123 | 476 | 660 | 1123
3645 | IDH2 | isocitrate dehydrogenase 2 (NADP+), mitochondrial | 6 | 0 | 15 | 15 | 15 | 15 | 15 | 15
1672 | CIC | capicua homolog (Drosophila) | 40 | 0 | 14 | 22 | 42 | 14 | 22 | 42
683 | ATRX | alpha thalassemia/mental retardation syndrome X-linked (RAD54 homolog, S. cerevisiae) | 78 | 0 | 13 | 17 | 22 | 13 | 17 | 22
9189 | ZNF844 | zinc finger protein 844 | 6 | 0 | 7 | 7 | 15 | 7 | 7 | 15
9084 | ZNF57 | zinc finger protein 57 | 7 | 0 | 6 | 6 | 14 | 6 | 6 | 14
2463 | EGFR | epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian) | 10 | 0 | 4 | 4 | 4 | 4 | 4 | 4
5968 | PIK3CA | phosphoinositide-3-kinase, catalytic, alpha polypeptide | 15 | 0 | 3 | 5 | 6 | 3 | 5 | 6
402 | ANKRD30A | ankyrin repeat domain 30A | 7 | 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: 95. 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 | REDUCTIVE_CARBOXYLATE_CYCLE_CO2_FIXATION |  | ACO1, ACO2, FH, IDH1, IDH2, MDH1, MDH2, SDHB, SUCLA2 | 9 | ACO1(2), ACO2(2), FH(1), IDH1(131), IDH2(6) | 2251788 | 142 | 138 | 9 | 0 | 126 | 5 | 0 | 11 | 0 | 0 | 1.11e-15 | <1.00e-15 | <1.01e-13
2 | 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(4), CDC25A(1), CDK2(1), CDK4(1), CHEK1(2), MYT1(2), RB1(4), TP53(113), WEE1(1) | 4452968 | 129 | 91 | 79 | 9 | 49 | 14 | 17 | 27 | 19 | 3 | 6.69e-08 | <1.00e-15 | <1.01e-13
3 | 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 | MAX(4), SP3(2), TP53(113), WT1(1) | 1784759 | 120 | 91 | 69 | 2 | 49 | 13 | 14 | 28 | 13 | 3 | 6.55e-15 | <1.00e-15 | <1.01e-13
4 | HSA00720_REDUCTIVE_CARBOXYLATE_CYCLE | Genes involved in reductive carboxylate cycle (CO2 fixation) | ACLY, ACO1, ACO2, ACSS1, ACSS2, FH, IDH1, IDH2, LOC441996, MDH1, MDH2, SUCLA2 | 11 | ACLY(3), ACO1(2), ACO2(2), ACSS1(1), ACSS2(3), FH(1), IDH1(131), IDH2(6) | 3363648 | 149 | 140 | 16 | 0 | 128 | 6 | 0 | 13 | 2 | 0 | 2.33e-15 | 1.11e-15 | 1.01e-13
5 | 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(10), IGF1R(3), POLR2A(3), PPP2CA(3), PRKCA(3), RB1(4), TEP1(5), TERF1(1), TP53(113), XRCC5(1) | 7123118 | 147 | 99 | 95 | 6 | 54 | 16 | 19 | 36 | 18 | 4 | 8.82e-14 | 1.11e-15 | 1.01e-13
6 | G1_TO_S_CELL_CYCLE_REACTOME |  | ATM, CCNA1, CCNB1, CCND1, CCND2, CCND3, CCNE1, CCNE2, CCNG2, CCNH, CDC25A, CDC45L, CDK2, CDK4, CDK7, CDKN1A, CDKN1B, CDKN1C, CDKN2A, CDKN2B, CDKN2C, CDKN2D, CREB3, CREB3L1, CREB3L3, CREB3L4, CREBL1, CREBL1, TNXB, E2F1, E2F2, E2F3, E2F4, E2F5, E2F6, FLJ14001, GADD45A, GBA2, MCM2, MCM3, MCM4, MCM5, MCM6, MCM7, MDM2, MNAT1, MYC, MYT1, NACA, NACA, FKSG17, ORC1L, ORC2L, ORC3L, ORC4L, ORC5L, ORC6L, PCNA, POLA2, POLE, POLE2, PRIM1, PRIM2A, RB1, RBL1, RPA1, RPA2, RPA3, TFDP1, TFDP2, TP53, WEE1 | 64 | ATM(4), CCNA1(1), CCND1(1), CCNE2(1), CCNG2(1), CCNH(2), CDC25A(1), CDK2(1), CDK4(1), CDKN1B(1), CDKN2A(2), CDKN2C(1), CREB3L1(1), E2F1(1), E2F3(1), E2F5(1), GBA2(1), MCM3(2), MCM4(3), MCM5(1), MCM6(1), MCM7(2), MDM2(2), MYT1(2), ORC1L(2), ORC2L(1), ORC3L(1), ORC4L(1), POLE(6), PRIM1(1), RB1(4), RBL1(2), RPA1(2), TNXB(9), TP53(113), WEE1(1) | 19490078 | 178 | 96 | 128 | 22 | 61 | 20 | 24 | 44 | 26 | 3 | 4.78e-08 | 1.22e-15 | 1.01e-13
7 | 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), CDK2(1), CDK4(1), CDKN1B(1), CDKN2A(2), CFL1(1), E2F1(1), MDM2(2), PRB1(2), TP53(113) | 2118324 | 126 | 89 | 76 | 7 | 49 | 14 | 17 | 28 | 15 | 3 | 2.42e-10 | 1.33e-15 | 1.01e-13
8 | CITRATE_CYCLE_TCA_CYCLE |  | ACO1, ACO2, CS, DLD, DLST, DLSTP, FH, IDH1, IDH2, IDH3A, IDH3B, IDH3G, MDH1, MDH2, PC, PCK1, SDHA, SDHA, SDHAL2, SDHB, SUCLA2, SUCLG1, SUCLG2 | 20 | ACO1(2), ACO2(2), FH(1), IDH1(131), IDH2(6), IDH3B(1), PC(1), PCK1(3), SUCLG2(1) | 5210151 | 148 | 138 | 15 | 2 | 128 | 8 | 0 | 12 | 0 | 0 | 3.00e-15 | 1.44e-15 | 1.01e-13
9 | HSA04210_APOPTOSIS | Genes involved in apoptosis | AIFM1, AKT1, AKT2, AKT3, APAF1, ATM, BAD, BAX, BCL2, BCL2L1, BID, BIRC2, BIRC3, BIRC4, CAPN1, CAPN2, CASP10, CASP3, CASP6, CASP7, CASP8, CASP9, CFLAR, CHP, CHUK, CSF2RB, CYCS, DFFA, DFFB, ENDOG, FADD, FAS, FASLG, IKBKB, IKBKG, IL1A, IL1B, IL1R1, IL1RAP, IL3, IL3RA, IRAK1, IRAK2, IRAK3, IRAK4, MAP3K14, MYD88, NFKB1, NFKB2, NFKBIA, NGFB, NTRK1, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRKACA, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, RELA, RIPK1, TNF, TNFRSF10A, TNFRSF10B, TNFRSF10C, TNFRSF10D, TNFRSF1A, TNFSF10, TP53, TRADD, TRAF2 | 80 | AIFM1(2), AKT1(1), APAF1(1), ATM(4), BAX(1), BIRC2(1), CFLAR(1), CYCS(2), DFFA(1), FAS(1), IL1B(1), IL1R1(1), IL1RAP(1), IL3RA(2), IRAK2(1), IRAK3(4), IRAK4(1), MAP3K14(1), NFKB1(1), NFKB2(1), PIK3CA(15), PIK3CB(1), PIK3CD(1), PIK3CG(4), PIK3R1(13), PIK3R2(1), PIK3R3(1), PIK3R5(1), PPP3CA(1), PPP3CC(1), PPP3R2(1), PRKAR1A(1), RELA(1), RIPK1(1), TNFRSF10D(1), TP53(113) | 21116382 | 186 | 109 | 129 | 28 | 57 | 27 | 27 | 42 | 30 | 3 | 5.36e-06 | 1.67e-15 | 1.01e-13
10 | 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(4), BAX(1), CCND1(1), CDK2(1), CDK4(1), E2F1(1), MDM2(2), RB1(4), TIMP3(2), TP53(113) | 4580868 | 131 | 92 | 81 | 6 | 49 | 14 | 19 | 29 | 17 | 3 | 9.58e-11 | 1.67e-15 | 1.01e-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 | HSA00902_MONOTERPENOID_BIOSYNTHESIS | Genes involved in monoterpenoid biosynthesis | CYP2C19, CYP2C9 | 2 | CYP2C19(4) | 512292 | 4 | 4 | 4 | 0 | 2 | 1 | 0 | 0 | 1 | 0 | 0.32 | 0.0019 | 1
2 | FLUMAZENILPATHWAY | Flumazenil is a benzodiazepine receptor antagonist that may induce protective preconditioning in ischemic cardiomyocytes. | GABRA1, GABRA2, GABRA3, GABRA4, GABRA5, GABRA6, GPX1, PRKCE, SOD1 | 9 | GABRA1(7), GABRA3(1), GABRA4(3), GABRA5(1), GABRA6(3) | 1995807 | 15 | 9 | 15 | 4 | 3 | 4 | 1 | 5 | 2 | 0 | 0.36 | 0.007 | 1
3 | 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 | CDK2(1), CDKN1B(1), CUL1(1), E2F1(1), RB1(4), SKP2(2), UBE2M(1) | 2167354 | 11 | 8 | 11 | 1 | 1 | 1 | 4 | 1 | 4 | 0 | 0.17 | 0.0082 | 1
4 | 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(1), CDC34(1), CDK2(1), CUL1(1), E2F1(1), RB1(4), SKP2(2) | 2161111 | 11 | 8 | 11 | 1 | 1 | 1 | 4 | 1 | 4 | 0 | 0.19 | 0.01 | 1
5 | UREACYCLEPATHWAY | Ammonia released from amino acid deamination is used to produce carbamoyl phosphate, which is used to convert ornithine to citrulline, from which urea is eventually formed. | ARG1, ASL, ASS, CPS1, GLS, GLUD1, GOT1 | 6 | ASL(2), CPS1(4), GLS(1), GLUD1(3), GOT1(2) | 1974792 | 12 | 6 | 12 | 2 | 1 | 2 | 0 | 5 | 4 | 0 | 0.44 | 0.028 | 1
6 | HSA00592_ALPHA_LINOLENIC_ACID_METABOLISM | Genes involved in alpha-Linolenic acid metabolism | ACOX1, ACOX3, FADS2, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6 | 15 | ACOX1(2), ACOX3(3), FADS2(2), PLA2G2D(1), PLA2G3(3), PLA2G4A(2), PLA2G5(1), PLA2G6(2) | 2562807 | 16 | 7 | 16 | 2 | 3 | 4 | 2 | 5 | 2 | 0 | 0.11 | 0.031 | 1
7 | PLCPATHWAY | Phospholipase C hydrolyzes the membrane lipid PIP2 to DAG, which activates protein kinase C, and IP3, which causes calcium influx. | AKT1, PIK3CA, PIK3R1, PLCB1, PLCG1, PRKCA, PRKCB1, VAV1 | 5 | AKT1(1), PLCB1(2), PLCG1(6), PRKCA(3), VAV1(3) | 2289050 | 15 | 10 | 14 | 3 | 4 | 3 | 2 | 4 | 1 | 1 | 0.26 | 0.034 | 1
8 | MALATEXPATHWAY | The tricarboxylate transfer pathway shuttles acetyl groups of acetyl-CoA between mitochondria and the cytoplasm. | ACLY, CS, MDH1, ME1, PC, PDHA1, SLC25A1, SLC25A11 | 8 | ACLY(3), ME1(1), PC(1), PDHA1(2), SLC25A1(1) | 2347660 | 8 | 7 | 8 | 0 | 1 | 2 | 0 | 3 | 2 | 0 | 0.068 | 0.041 | 1
9 | SLRPPATHWAY | Small leucine-rich proteoglycans (SLRPs) interact with and reorganize collagen fibers in the extracellular matrix. | BGN, DCN, DSPG3, FMOD, KERA, LUM | 5 | BGN(2), DCN(1), FMOD(1), LUM(2) | 917147 | 6 | 5 | 6 | 2 | 1 | 1 | 0 | 4 | 0 | 0 | 0.69 | 0.054 | 1
10 | HSA00232_CAFFEINE_METABOLISM | Genes involved in caffeine metabolism | CYP1A2, CYP2A13, CYP2A6, CYP2A7, NAT1, NAT2, XDH | 7 | CYP1A2(1), NAT1(1), NAT2(2), XDH(7) | 2013925 | 11 | 6 | 11 | 0 | 3 | 1 | 0 | 5 | 2 | 0 | 0.052 | 0.055 | 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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