Kidney Renal Papillary Cell Carcinoma: 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: KIRP-TP

- Number of patients in set: 100

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:KIRP-TP.final_analysis_set.maf

- Significantly mutated genes (q ≤ 0.1): 7

- Mutations seen in COSMIC: 39

- Significantly mutated genes in COSMIC territory: 3

- Genes with clustered mutations (≤ 3 aa apart): 28

- Significantly mutated genesets: 0

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

Mutation Preprocessing

- Read 100 MAFs of type "Broad"

- Total number of mutations in input MAFs: 9057

- After removing 42 mutations outside chr1-24: 9015

- After removing 318 blacklisted mutations: 8697

- After removing 225 noncoding mutations: 8472

- After collapsing adjacent/redundant mutations: 7282

Mutation Filtering

- Number of mutations before filtering: 7282

- After removing 111 mutations outside gene set: 7171

- After removing 5 mutations outside category set: 7166

Results
Breakdown of Mutations by Type

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

type | count
--- | ---
Frame_Shift_Del | 473
Frame_Shift_Ins | 172
In_Frame_Del | 111
In_Frame_Ins | 26
Missense_Mutation | 4399
Nonsense_Mutation | 249
Nonstop_Mutation | 4
Silent | 1558
Splice_Site | 163
Translation_Start_Site | 11
Total | 7166

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 | 473 | 166314389 | 2.8e-06 | 2.8 | 1.5 | 2.1
*Cp(A/C/T)->T | 837 | 1347410459 | 6.2e-07 | 0.62 | 0.33 | 1.7
A->G | 786 | 1448486319 | 5.4e-07 | 0.54 | 0.29 | 2.3
transver | 2314 | 2962211167 | 7.8e-07 | 0.78 | 0.41 | 5
indel+null | 1193 | 2962211167 | 4e-07 | 0.4 | 0.21 | NaN
double_null | 5 | 2962211167 | 1.7e-09 | 0.0017 | 0.00089 | NaN
Total | 5608 | 2962211167 | 1.9e-06 | 1.9 | 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: KIRP-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: 7. 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 | CDC27 | cell division cycle 27 homolog (S. cerevisiae) | 250946 | 4 | 4 | 1 | 0 | 0 | 0 | 0 | 0 | 4 | 0 | 0.00055 | 1 | 0.083 | 0 | <1.00e-15 | <1.81e-11
2 | MET | met proto-oncogene (hepatocyte growth factor receptor) | 427226 | 8 | 8 | 7 | 0 | 0 | 3 | 2 | 3 | 0 | 0 | 3.4e-07 | 0.078 | 0.0044 | 0.00041 | 3.33e-09 | 3.02e-05
3 | IL32 | interleukin 32 | 55560 | 4 | 4 | 2 | 0 | 0 | 0 | 0 | 0 | 4 | 0 | 2.1e-06 | 1 | 0.92 | 0.00022 | 1.03e-08 | 6.22e-05
4 | PCF11 | PCF11, cleavage and polyadenylation factor subunit, homolog (S. cerevisiae) | 425608 | 8 | 7 | 7 | 1 | 0 | 1 | 4 | 3 | 0 | 0 | 7e-06 | 0.16 | 0.85 | 0.00073 | 1.03e-07 | 0.000468
5 | SFRS2IP | splicing factor, arginine/serine-rich 2, interacting protein | 442110 | 5 | 5 | 2 | 1 | 0 | 0 | 0 | 1 | 4 | 0 | 0.00015 | 0.98 | 0.0012 | 0.000081 | 2.29e-07 | 0.000830
6 | NF2 | neurofibromin 2 (merlin) | 162737 | 6 | 6 | 6 | 0 | 0 | 0 | 0 | 0 | 6 | 0 | 1.6e-07 | 0.43 | 0.78 | 0.3 | 8.63e-07 | 0.00260
7 | LGI4 | leucine-rich repeat LGI family, member 4 | 70745 | 4 | 4 | 4 | 0 | 0 | 1 | 1 | 2 | 0 | 0 | 7.3e-06 | 0.28 | 0.018 | 0.068 | 7.75e-06 | 0.0201
8 | PARD6B | par-6 partitioning defective 6 homolog beta (C. elegans) | 106100 | 4 | 4 | 4 | 0 | 0 | 0 | 2 | 0 | 2 | 0 | 0.000011 | 0.26 | 0.74 | 0.98 | 0.000133 | 0.301
9 | NFE2L2 | nuclear factor (erythroid-derived 2)-like 2 | 178107 | 3 | 3 | 3 | 0 | 0 | 0 | 1 | 2 | 0 | 0 | 0.0028 | 0.46 | 0.013 | 0.0048 | 0.000167 | 0.337
10 | SAV1 | salvador homolog 1 (Drosophila) | 115810 | 3 | 3 | 3 | 0 | 0 | 1 | 0 | 0 | 2 | 0 | 0.00011 | 0.74 | 0.98 | 0.18 | 0.000223 | 0.404
11 | CD86 | CD86 molecule | 101158 | 3 | 3 | 3 | 0 | 1 | 0 | 0 | 1 | 1 | 0 | 0.00012 | 0.6 | 0.11 | 0.25 | 0.000349 | 0.528
12 | POMC | proopiomelanocortin (adrenocorticotropin/ beta-lipotropin/ alpha-melanocyte stimulating hormone/ beta-melanocyte stimulating hormone/ beta-endorphin) | 57272 | 3 | 3 | 3 | 0 | 1 | 0 | 0 | 1 | 1 | 0 | 8e-05 | 0.51 | 0.53 | 0.38 | 0.000349 | 0.528
13 | FLJ46321 | family with sequence similarity 75, member D1 | 462549 | 6 | 6 | 6 | 1 | 0 | 0 | 1 | 3 | 2 | 0 | 0.00022 | 0.54 | 0.73 | 0.15 | 0.000383 | 0.533
14 | NSUN2 | NOL1/NOP2/Sun domain family, member 2 | 227978 | 4 | 4 | 4 | 0 | 0 | 2 | 0 | 1 | 1 | 0 | 0.00018 | 0.32 | 0.22 | 0.25 | 0.000492 | 0.554
15 | KDM6A | lysine (K)-specific demethylase 6A | 393801 | 5 | 5 | 5 | 0 | 0 | 0 | 0 | 0 | 4 | 1 | 0.000077 | 0.52 | 0.52 | 0.59 | 0.000504 | 0.554
16 | POTEH | POTE ankyrin domain family, member H | 90750 | 3 | 3 | 2 | 0 | 0 | 0 | 0 | 2 | 1 | 0 | 0.00038 | 0.66 | 0.99 | 0.13 | 0.000525 | 0.554
17 | EBF2 | early B-cell factor 2 | 173115 | 3 | 3 | 3 | 1 | 0 | 0 | 0 | 3 | 0 | 0 | 0.0045 | 0.8 | 0.26 | 0.011 | 0.000541 | 0.554
18 | BRAF | v-raf murine sarcoma viral oncogene homolog B1 | 222693 | 4 | 4 | 4 | 0 | 0 | 0 | 1 | 3 | 0 | 0 | 0.00067 | 0.36 | 0.46 | 0.076 | 0.000551 | 0.554
19 | ACSBG2 | acyl-CoA synthetase bubblegum family member 2 | 202529 | 4 | 4 | 2 | 0 | 1 | 0 | 0 | 3 | 0 | 0 | 0.00042 | 0.36 | 1 | 0.13 | 0.000589 | 0.562
20 | PEBP1 | phosphatidylethanolamine binding protein 1 | 43928 | 2 | 2 | 2 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0.0026 | 0.49 | 0.21 | 0.024 | 0.000664 | 0.594
21 | SLC5A12 | solute carrier family 5 (sodium/glucose cotransporter), member 12 | 181746 | 4 | 4 | 4 | 1 | 0 | 0 | 2 | 2 | 0 | 0 | 0.0003 | 0.58 | 0.46 | 0.22 | 0.000700 | 0.594
22 | BAT2L2 |  | 640972 | 4 | 4 | 4 | 0 | 0 | 2 | 1 | 0 | 1 | 0 | 0.011 | 0.27 | 0.021 | 0.0062 | 0.000721 | 0.594
23 | LYAR | Ly1 antibody reactive homolog (mouse) | 117200 | 2 | 2 | 2 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0.002 | 0.62 | 0.12 | 0.037 | 0.000760 | 0.598
24 | CHCHD3 | coiled-coil-helix-coiled-coil-helix domain containing 3 | 63374 | 3 | 3 | 3 | 0 | 0 | 1 | 0 | 2 | 0 | 0 | 0.000089 | 0.46 | 0.68 | 1 | 0.000919 | 0.694
25 | GLCCI1 | glucocorticoid induced transcript 1 | 124058 | 2 | 2 | 1 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0.02 | 0.68 | 0.013 | 0.0055 | 0.00110 | 0.796
26 | ACTB | actin, beta | 114798 | 3 | 3 | 3 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 0.00013 | 0.66 | 0.95 | 1 | 0.00131 | 0.881
27 | BAP1 | BRCA1 associated protein-1 (ubiquitin carboxy-terminal hydrolase) | 205639 | 4 | 4 | 4 | 1 | 0 | 2 | 1 | 0 | 1 | 0 | 0.00022 | 0.62 | 0.53 | 0.61 | 0.00133 | 0.881
28 | BHMT | betaine-homocysteine methyltransferase | 124685 | 3 | 3 | 3 | 0 | 0 | 0 | 2 | 0 | 1 | 0 | 0.00034 | 0.46 | 0.056 | 0.4 | 0.00137 | 0.881
29 | ADAP2 | ArfGAP with dual PH domains 2 | 109161 | 2 | 2 | 2 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0.0027 | 0.78 | 0.22 | 0.056 | 0.00146 | 0.881
30 | ACADL | acyl-Coenzyme A dehydrogenase, long chain | 122884 | 3 | 3 | 3 | 0 | 0 | 1 | 1 | 0 | 1 | 0 | 0.00022 | 0.47 | 0.29 | 0.67 | 0.00148 | 0.881
31 | DNAJC25-GNG10 |  | 12971 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0.0015 | 0.66 | NaN | NaN | 0.00151 | 0.881
32 | IFNA16 | interferon, alpha 16 | 57162 | 2 | 2 | 1 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0.0036 | 0.48 | 0.16 | 0.048 | 0.00167 | 0.945
33 | CNFN | cornifelin | 26367 | 1 | 1 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0.0018 | 0.85 | NaN | NaN | 0.00176 | 0.967
34 | ZFP14 | zinc finger protein 14 homolog (mouse) | 161788 | 3 | 3 | 3 | 0 | 0 | 2 | 0 | 1 | 0 | 0 | 0.0012 | 0.44 | 0.12 | 0.18 | 0.00201 | 1.000
35 | SMARCB1 | SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily b, member 1 | 115899 | 3 | 3 | 3 | 0 | 0 | 1 | 0 | 0 | 2 | 0 | 0.00032 | 0.53 | 0.61 | 0.7 | 0.00207 | 1.000

CDC27

Figure S1. This figure depicts the distribution of mutations and mutation types across the CDC27 significant gene.

MET

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

IL32

Figure S3. This figure depicts the distribution of mutations and mutation types across the IL32 significant gene.

PCF11

Figure S4. This figure depicts the distribution of mutations and mutation types across the PCF11 significant gene.

NF2

Figure S5. This figure depicts the distribution of mutations and mutation types across the NF2 significant gene.

LGI4

Figure S6. This figure depicts the distribution of mutations and mutation types across the LGI4 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: 3. Number of genes displayed: 10

rank | gene | description | n | cos | n_cos | N_cos | cos_ev | p | q
--- | --- | --- | --- | --- | --- | --- | --- | --- | ---
1 | MET | met proto-oncogene (hepatocyte growth factor receptor) | 8 | 34 | 4 | 3400 | 12 | 7.1e-11 | 3.2e-07
2 | FGFR3 | fibroblast growth factor receptor 3 (achondroplasia, thanatophoric dwarfism) | 4 | 62 | 3 | 6200 | 1469 | 2.7e-07 | 0.0006
3 | SMARCA4 | SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4 | 4 | 30 | 2 | 3000 | 3 | 0.000016 | 0.024
4 | BRAF | v-raf murine sarcoma viral oncogene homolog B1 | 4 | 89 | 2 | 8900 | 14380 | 0.00014 | 0.11
5 | NF2 | neurofibromin 2 (merlin) | 6 | 550 | 3 | 55000 | 15 | 0.00017 | 0.11
6 | CDCA8 | cell division cycle associated 8 | 1 | 1 | 1 | 100 | 1 | 0.00019 | 0.11
7 | FLCN | folliculin | 1 | 1 | 1 | 100 | 1 | 0.00019 | 0.11
8 | PLXDC2 | plexin domain containing 2 | 1 | 1 | 1 | 100 | 1 | 0.00019 | 0.11
9 | SMARCB1 | SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily b, member 1 | 3 | 129 | 2 | 12900 | 8 | 0.00029 | 0.15
10 | PTEN | phosphatase and tensin homolog (mutated in multiple advanced cancers 1) | 3 | 767 | 3 | 76700 | 27 | 0.00046 | 0.21

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
--- | --- | --- | --- | --- | --- | --- | --- | --- | --- | ---
48 | ACSBG2 | acyl-CoA synthetase bubblegum family member 2 | 4 | 0 | 3 | 3 | 3 | 3 | 3 | 3
2156 | MET | met proto-oncogene (hepatocyte growth factor receptor) | 8 | 0 | 1 | 3 | 4 | 1 | 3 | 4
2643 | PCF11 | PCF11, cleavage and polyadenylation factor subunit, homolog (S. cerevisiae) | 8 | 0 | 1 | 2 | 10 | 1 | 2 | 10
2335 | NBPF9 | neuroblastoma breakpoint family, member 9 | 2 | 0 | 1 | 1 | 1 | 1 | 1 | 1
2675 | PEBP1 | phosphatidylethanolamine binding protein 1 | 2 | 0 | 1 | 1 | 1 | 1 | 1 | 1
2678 | PER1 | period homolog 1 (Drosophila) | 2 | 0 | 1 | 1 | 1 | 1 | 1 | 1
2820 | POTEH | POTE ankyrin domain family, member H | 3 | 0 | 1 | 1 | 1 | 1 | 1 | 1
3044 | RETSAT | retinol saturase (all-trans-retinol 13,14-reductase) | 2 | 0 | 1 | 1 | 1 | 1 | 1 | 1
4159 | ZNF423 | zinc finger protein 423 | 4 | 0 | 1 | 1 | 1 | 1 | 1 | 1
4196 | ZNF599 | zinc finger protein 599 | 2 | 0 | 1 | 1 | 1 | 1 | 1 | 1

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: 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 | MTORPATHWAY | Mammalian target of rapamycin (mTOR) senses mitogenic factors and nutrients, including ATP, and induces cell proliferation. | AKT1, EIF3S10, EIF4A1, EIF4A2, EIF4B, EIF4E, EIF4EBP1, EIF4G1, EIF4G2, EIF4G3, FKBP1A, FRAP1, MKNK1, PDK2, PDPK1, PIK3CA, PIK3R1, PPP2CA, PTEN, RPS6, RPS6KB1, TSC1, TSC2 | 21 | EIF4B(2), EIF4G1(2), EIF4G3(4), PIK3CA(2), PIK3R1(1), PTEN(3), TSC1(2), TSC2(4) | 4154558 | 20 | 18 | 20 | 2 | 2 | 6 | 3 | 3 | 6 | 0 | 0.053 | 0.00096 | 0.6
2 | ALANINE_AND_ASPARTATE_METABOLISM |  | AARS, ABAT, ADSL, ADSS, AGXT, AGXT2, ASL, ASNS, ASPA, ASS, CAD, CRAT, DARS, DDO, GAD1, GAD2, GOT1, GOT2, GPT, GPT2, NARS, PC | 21 | AARS(1), ADSL(1), AGXT(1), AGXT2(1), CAD(3), CRAT(1), DARS(3), DDO(1), GOT2(1), GPT(1), PC(4) | 3908660 | 18 | 16 | 18 | 1 | 1 | 3 | 1 | 8 | 5 | 0 | 0.057 | 0.0031 | 0.68
3 | NEUTROPHILPATHWAY | Neutrophils are phagocytotic leukocytes that destroy foreign cells with reactive oxygen species or enzymatic digestion and express CD11 and CD18. | CD44, ICAM1, ITGAL, ITGAM, ITGB2, PECAM1, SELE, SELL | 8 | ITGAL(3), ITGAM(2), ITGB2(1), SELE(1), SELL(1) | 1554500 | 8 | 8 | 8 | 0 | 1 | 2 | 0 | 3 | 2 | 0 | 0.13 | 0.0059 | 0.68
4 | KREBPATHWAY | The Krebs (citric acid) cycle takes place in mitochondria, where it extracts energy in the form of electron carriers NADH and FADH2, which drive the electron transport chain. | ACO2, CS, FH, IDH2, MDH1, OGDH, SDHA, SUCLA2 | 8 | FH(1), IDH2(1), MDH1(1), OGDH(2), SDHA(2) | 1404132 | 7 | 7 | 7 | 0 | 0 | 3 | 0 | 1 | 3 | 0 | 0.072 | 0.0062 | 0.68
5 | METHIONINE_METABOLISM |  | AHCY, BHMT, CBS, CTH, DNMT1, DNMT2, DNMT3A, DNMT3B, MARS, MARS2, MAT1A, MAT2B, MTR | 12 | AHCY(1), BHMT(3), CTH(1), DNMT1(1), DNMT3A(1), DNMT3B(1), MARS(1), MARS2(1), MAT2B(1) | 2607651 | 11 | 11 | 11 | 1 | 0 | 1 | 3 | 3 | 4 | 0 | 0.38 | 0.0064 | 0.68
6 | SIG_PIP3_SIGNALING_IN_CARDIAC_MYOCTES | Genes related to PIP3 signaling in cardiac myocytes | AKT1, AKT2, AKT3, BAD, BCL2L1, CDC42, CDK2, CDKN1B, CDKN2A, CREB1, CREB3, CREB5, EBP, ERBB4, F2RL2, FOXO3A, FRAP1, GAB1, GADD45A, GRB2, GSK3A, GSK3B, IFI27, IGF1, IGFBP1, INPPL1, IRS1, IRS2, IRS4, MET, MYC, NOLC1, P101-PI3K, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PARD3, PARD6A, PDK1, PIK3CA, PIK3CD, PPP1R13B, PREX1, PSCD3, PTEN, PTK2, PTPN1, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KB1, SFN, SHC1, SLC2A4, SOS1, SOS2, TSC1, TSC2, YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ, YWHAZ | 63 | AKT2(1), CDKN2A(1), CREB3(1), ERBB4(2), F2RL2(1), INPPL1(1), IRS1(1), MET(8), MYC(1), NOLC1(1), PAK1(1), PAK3(2), PAK4(1), PARD3(1), PIK3CA(2), PIK3CD(1), PTEN(3), PTPN1(1), RPS6KA1(1), RPS6KA3(1), SFN(1), SOS1(2), SOS2(1), TSC1(2), TSC2(4) | 11606420 | 42 | 35 | 41 | 4 | 4 | 11 | 9 | 9 | 9 | 0 | 0.0018 | 0.0073 | 0.68
7 | CBLPATHWAY | Activated EGF receptors undergo endocytosis into clathrin-coated vesicles, where they are recycled to the membrane or ubiquitinated by Cbl. | CBL, CSF1R, EGF, EGFR, GRB2, MET, PDGFRA, PRKCA, PRKCB1, SH3GLB1, SH3GLB2, SH3KBP1, SRC | 12 | EGF(1), MET(8), PDGFRA(2), SH3KBP1(1) | 2906209 | 12 | 11 | 11 | 1 | 1 | 3 | 2 | 5 | 1 | 0 | 0.13 | 0.0077 | 0.68
8 | RABPATHWAY | Rab family GTPases regulate vesicle transport, endocytosis and exocytosis, and vesicle docking via interactions with the rabphilins. | ACTA1, MEL, RAB11A, RAB1A, RAB2, RAB27A, RAB3A, RAB4A, RAB5A, RAB6A, RAB7, RAB9A | 9 | ACTA1(1), RAB11A(1), RAB3A(1), RAB6A(1) | 636136 | 4 | 4 | 4 | 1 | 0 | 1 | 0 | 2 | 1 | 0 | 0.81 | 0.015 | 1
9 | 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(1), DLD(1), FH(1), IDH2(1), MDH1(1), PC(4), PCK1(1), SDHA(2) | 3076072 | 12 | 11 | 12 | 0 | 0 | 2 | 1 | 3 | 6 | 0 | 0.049 | 0.017 | 1
10 | LYMPHOCYTEPATHWAY | B and T cell lymphocytes interact with other cells via transmembrane adhesion proteins such as CD44, which interacts with endothelial cells. | CD44, ICAM1, ITGA4, ITGAL, ITGB1, ITGB2, PECAM1, SELE, SELL | 9 | ITGA4(1), ITGAL(3), ITGB2(1), SELE(1), SELL(1) | 1800417 | 7 | 7 | 7 | 1 | 1 | 2 | 1 | 1 | 2 | 0 | 0.41 | 0.018 | 1

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 | MTORPATHWAY | Mammalian target of rapamycin (mTOR) senses mitogenic factors and nutrients, including ATP, and induces cell proliferation. | AKT1, EIF3S10, EIF4A1, EIF4A2, EIF4B, EIF4E, EIF4EBP1, EIF4G1, EIF4G2, EIF4G3, FKBP1A, FRAP1, MKNK1, PDK2, PDPK1, PIK3CA, PIK3R1, PPP2CA, PTEN, RPS6, RPS6KB1, TSC1, TSC2 | 21 | EIF4B(2), EIF4G1(2), EIF4G3(4), PIK3CA(2), PIK3R1(1), PTEN(3), TSC1(2), TSC2(4) | 4154558 | 20 | 18 | 20 | 2 | 2 | 6 | 3 | 3 | 6 | 0 | 0.053 | 0.00096 | 0.6
2 | ALANINE_AND_ASPARTATE_METABOLISM |  | AARS, ABAT, ADSL, ADSS, AGXT, AGXT2, ASL, ASNS, ASPA, ASS, CAD, CRAT, DARS, DDO, GAD1, GAD2, GOT1, GOT2, GPT, GPT2, NARS, PC | 21 | AARS(1), ADSL(1), AGXT(1), AGXT2(1), CAD(3), CRAT(1), DARS(3), DDO(1), GOT2(1), GPT(1), PC(4) | 3908660 | 18 | 16 | 18 | 1 | 1 | 3 | 1 | 8 | 5 | 0 | 0.057 | 0.0031 | 0.79
3 | NEUTROPHILPATHWAY | Neutrophils are phagocytotic leukocytes that destroy foreign cells with reactive oxygen species or enzymatic digestion and express CD11 and CD18. | CD44, ICAM1, ITGAL, ITGAM, ITGB2, PECAM1, SELE, SELL | 8 | ITGAL(3), ITGAM(2), ITGB2(1), SELE(1), SELL(1) | 1554500 | 8 | 8 | 8 | 0 | 1 | 2 | 0 | 3 | 2 | 0 | 0.13 | 0.0059 | 0.79
4 | KREBPATHWAY | The Krebs (citric acid) cycle takes place in mitochondria, where it extracts energy in the form of electron carriers NADH and FADH2, which drive the electron transport chain. | ACO2, CS, FH, IDH2, MDH1, OGDH, SDHA, SUCLA2 | 8 | FH(1), IDH2(1), MDH1(1), OGDH(2), SDHA(2) | 1404132 | 7 | 7 | 7 | 0 | 0 | 3 | 0 | 1 | 3 | 0 | 0.072 | 0.0062 | 0.79
5 | METHIONINE_METABOLISM |  | AHCY, BHMT, CBS, CTH, DNMT1, DNMT2, DNMT3A, DNMT3B, MARS, MARS2, MAT1A, MAT2B, MTR | 12 | AHCY(1), BHMT(3), CTH(1), DNMT1(1), DNMT3A(1), DNMT3B(1), MARS(1), MARS2(1), MAT2B(1) | 2607651 | 11 | 11 | 11 | 1 | 0 | 1 | 3 | 3 | 4 | 0 | 0.38 | 0.0064 | 0.79
6 | RABPATHWAY | Rab family GTPases regulate vesicle transport, endocytosis and exocytosis, and vesicle docking via interactions with the rabphilins. | ACTA1, MEL, RAB11A, RAB1A, RAB2, RAB27A, RAB3A, RAB4A, RAB5A, RAB6A, RAB7, RAB9A | 9 | ACTA1(1), RAB11A(1), RAB3A(1), RAB6A(1) | 636136 | 4 | 4 | 4 | 1 | 0 | 1 | 0 | 2 | 1 | 0 | 0.81 | 0.015 | 1
7 | 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(1), DLD(1), FH(1), IDH2(1), MDH1(1), PC(4), PCK1(1), SDHA(2) | 3076072 | 12 | 11 | 12 | 0 | 0 | 2 | 1 | 3 | 6 | 0 | 0.049 | 0.017 | 1
8 | LYMPHOCYTEPATHWAY | B and T cell lymphocytes interact with other cells via transmembrane adhesion proteins such as CD44, which interacts with endothelial cells. | CD44, ICAM1, ITGA4, ITGAL, ITGB1, ITGB2, PECAM1, SELE, SELL | 9 | ITGA4(1), ITGAL(3), ITGB2(1), SELE(1), SELL(1) | 1800417 | 7 | 7 | 7 | 1 | 1 | 2 | 1 | 1 | 2 | 0 | 0.41 | 0.018 | 1
9 | MONOCYTEPATHWAY | Monocytes are a class of immune phagocytes that can develop into macrophages and express LFA-1, CD44, and other surface signaling proteins. | CD44, ICAM1, ITGA4, ITGAL, ITGAM, ITGB1, ITGB2, PECAM1, SELE, SELL, SELP | 11 | ITGA4(1), ITGAL(3), ITGAM(2), ITGB2(1), SELE(1), SELL(1) | 2377487 | 9 | 9 | 9 | 1 | 1 | 2 | 1 | 3 | 2 | 0 | 0.32 | 0.019 | 1
10 | ST_G_ALPHA_S_PATHWAY | The G-alpha-s protein activates adenylyl cyclases, which catalyze cAMP formation. | ASAH1, BF, BFAR, BRAF, CAMP, CREB1, CREB3, CREB5, EPAC, GAS, GRF2, MAPK1, RAF1, SNX13, SRC, TERF2IP | 12 | BFAR(1), BRAF(4), CREB3(1), RAF1(1), SNX13(1), TERF2IP(1) | 1676241 | 9 | 7 | 9 | 1 | 0 | 0 | 3 | 5 | 1 | 0 | 0.35 | 0.02 | 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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