Kidney Renal Clear 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: KIRC.

Number of patients in set: 293

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: KIRC.final_analysis_set.maf

Significantly mutated genes (q ≤ 0.1): 84

Mutations seen in COSMIC: 345

Significantly mutated genes in COSMIC territory: 85

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

Significantly mutated genesets: 6

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

Mutation Preprocessing

Read 293 MAFs of type "Broad"

Read 66 MAFs of type "Baylor"

Total number of mutations in input MAFs: 99658

After removing 232 mutations outside chr1-24: 99426

After removing 70518 noncoding mutations: 28908

After collapsing adjacent/redundant mutations: 26038

Mutation Filtering

Number of mutations before filtering: 26038

After removing 802 mutations outside gene set: 25236

After removing 111 mutations outside category set: 25125

After removing 1 "impossible" mutations in

gene-patient-category bins of zero coverage: 25124

Results
Breakdown of Mutations by Type

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

type | count
--- | ---
Frame_Shift_Del | 440
Frame_Shift_Ins | 114
In_Frame_Del | 129
In_Frame_Ins | 43
Missense_Mutation | 16106
Nonsense_Mutation | 1080
Nonstop_Mutation | 21
Silent | 6625
Splice_Site | 525
Translation_Start_Site | 42
Total | 25125

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 | 1767 | 484078369 | 3.7e-06 | 3.7 | 1.7 | 2.1
*ApG->G | 1226 | 1342141277 | 9.1e-07 | 0.91 | 0.43 | 2.1
*Np(A/C/T)->transit | 5303 | 6921093572 | 7.7e-07 | 0.77 | 0.36 | 2
transver | 7785 | 8747313218 | 8.9e-07 | 0.89 | 0.42 | 5
indel+null | 2411 | 8747313218 | 2.8e-07 | 0.28 | 0.13 | NaN
double_null | 8 | 8747313218 | 9.1e-10 | 0.00091 | 0.00043 | NaN
Total | 18500 | 8747313218 | 2.1e-06 | 2.1 | 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: KIRC.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

Table 3. Get Full Table A Ranked List of Significantly Mutated Genes. Number of significant genes found: 84. 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 | VHL | von Hippel-Lindau tumor suppressor | 123072 | 150 | 146 | 96 | 2 | 2 | 14 | 15 | 33 | 86 | 0 | <1.00e-15 | 2.3e-11 | 0.042 | 0.00084 | 0.0011 | <0.00 | <0.00
2 | KDM5C |  | 1253863 | 18 | 18 | 18 | 1 | 0 | 0 | 2 | 5 | 11 | 0 | 1.44e-15 | 0.1 | 0.0066 | 0.29 | 0.012 | 6.66e-16 | 2.59e-12
3 | PBRM1 | polybromo 1 | 1470408 | 100 | 98 | 98 | 2 | 0 | 1 | 6 | 15 | 78 | 0 | <1.00e-15 | 0.000013 | 0.037 | 0.09 | 0.022 | <8.88e-16 | <2.59e-12
4 | RRAD | Ras-related associated with diabetes | 202274 | 4 | 4 | 1 | 0 | 0 | 0 | 0 | 4 | 0 | 0 | 0.00016 | 0.43 | 4e-07 | 0.001 | 0 | <1.00e-15 | <2.59e-12
5 | SV2C | synaptic vesicle glycoprotein 2C | 653960 | 3 | 3 | 3 | 0 | 0 | 1 | 1 | 0 | 1 | 0 | 0.061 | 0.3 | 0.14 | 0.0017 | 0 | <1.00e-15 | <2.59e-12
6 | TOR1A | torsin family 1, member A (torsin A) | 280456 | 3 | 3 | 1 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 0.0067 | 0.27 | 4.8e-06 | 0.0012 | 0 | <1.00e-15 | <2.59e-12
7 | TPST1 | tyrosylprotein sulfotransferase 1 | 330797 | 2 | 2 | 2 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0.031 | 0.74 | 0.08 | 0.00085 | 0 | <1.00e-15 | <2.59e-12
8 | BAP1 | BRCA1 associated protein-1 (ubiquitin carboxy-terminal hydrolase) | 589189 | 28 | 27 | 25 | 1 | 0 | 2 | 6 | 5 | 14 | 1 | 1.11e-15 | 0.0024 | 0.067 | 0.23 | 0.067 | 2.78e-15 | 6.29e-12
9 | SETD2 | SET domain containing 2 | 1866089 | 32 | 32 | 32 | 1 | 2 | 2 | 2 | 7 | 18 | 1 | <1.00e-15 | 0.0039 | 0.33 | 0.091 | 0.16 | <6.00e-15 | <1.21e-11
10 | PTEN | phosphatase and tensin homolog (mutated in multiple advanced cancers 1) | 365609 | 16 | 15 | 16 | 2 | 0 | 1 | 5 | 3 | 7 | 0 | <1.00e-15 | 0.11 | 0.11 | 0.91 | 0.18 | <6.88e-15 | <1.25e-11
11 | PIK3CA | phosphoinositide-3-kinase, catalytic, alpha polypeptide | 963086 | 14 | 14 | 13 | 1 | 0 | 2 | 6 | 5 | 1 | 0 | 1.28e-10 | 0.061 | 0.0014 | 0.21 | 0.0014 | 5.58e-12 | 9.19e-09
12 | STAG3L2 | stromal antigen 3-like 2 | 83876 | 6 | 6 | 2 | 0 | 0 | 0 | 0 | 0 | 6 | 0 | 7.40e-11 | 1 | 0.0051 | 0.16 | 0.0068 | 1.47e-11 | 2.21e-08
13 | MTOR |  | 2294678 | 26 | 24 | 22 | 2 | 1 | 2 | 4 | 19 | 0 | 0 | 8.13e-11 | 0.043 | 0.0045 | 0.51 | 0.011 | 2.50e-11 | 3.49e-08
14 | EBPL | emopamil binding protein-like | 139558 | 7 | 6 | 3 | 0 | 1 | 0 | 0 | 6 | 0 | 0 | 2.76e-08 | 0.2 | 0.0019 | 1 | 0.004 | 2.66e-09 | 3.44e-06
15 | KANK3 | KN motif and ankyrin repeat domains 3 | 301372 | 6 | 6 | 2 | 0 | 0 | 0 | 0 | 0 | 6 | 0 | 4.25e-09 | 1 | 0.043 | 0.64 | 0.098 | 9.38e-09 | 0.000011
16 | NUDT11 | nudix (nucleoside diphosphate linked moiety X)-type motif 11 | 127356 | 3 | 3 | 1 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 0.00019 | 1 | 3.8e-06 | 0.96 | 6.2e-06 | 2.52e-08 | 0.000029
17 | ANKRD36 | ankyrin repeat domain 36 | 752950 | 11 | 10 | 6 | 2 | 1 | 0 | 0 | 9 | 1 | 0 | 5.78e-07 | 0.52 | 0.0011 | 0.83 | 0.003 | 3.70e-08 | 0.000039
18 | ZCCHC3 | zinc finger, CCHC domain containing 3 | 208403 | 3 | 3 | 1 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 0.00017 | 1 | 2.2e-06 | 1 | 0.000012 | 4.35e-08 | 0.000044
19 | FAM174B |  | 72325 | 3 | 3 | 1 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 0.00011 | 1 | 0.000018 | 0.97 | 2e-05 | 4.67e-08 | 0.000044
20 | TSPAN19 | tetraspanin 19 | 144817 | 4 | 4 | 4 | 0 | 0 | 0 | 1 | 1 | 2 | 0 | 5.22e-07 | 0.6 | 0.016 | 0.25 | 0.033 | 3.26e-07 | 0.00030
21 | DACH2 | dachshund homolog 2 (Drosophila) | 506733 | 7 | 7 | 3 | 0 | 0 | 0 | 0 | 7 | 0 | 0 | 5.94e-06 | 0.27 | 0.0014 | 0.2 | 0.0032 | 3.61e-07 | 0.00030
22 | KRTAP1-1 | keratin associated protein 1-1 | 157631 | 3 | 3 | 1 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 0.00090 | 0.62 | 6e-06 | 0.8 | 0.000021 | 3.63e-07 | 0.00030
23 | UQCRFS1 | ubiquinol-cytochrome c reductase, Rieske iron-sulfur polypeptide 1 | 180195 | 3 | 3 | 1 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 0.0028 | 0.31 | 8.8e-06 | 1 | 0.000012 | 6.31e-07 | 0.00050
24 | VCX2 | variable charge, X-linked 2 | 46999 | 4 | 3 | 4 | 0 | 0 | 1 | 0 | 1 | 2 | 0 | 4.46e-06 | 0.67 | 0.0066 | 0.82 | 0.018 | 1.40e-06 | 0.0011
25 | CR1 | complement component (3b/4b) receptor 1 (Knops blood group) | 1444581 | 11 | 11 | 8 | 0 | 1 | 0 | 0 | 4 | 6 | 0 | 2.65e-06 | 0.095 | 0.073 | 0.059 | 0.039 | 1.79e-06 | 0.0013
26 | KRT1 | keratin 1 (epidermolytic hyperkeratosis) | 500192 | 5 | 5 | 2 | 0 | 1 | 0 | 0 | 0 | 4 | 0 | 0.000083 | 0.72 | 0.0008 | 0.98 | 0.0026 | 3.48e-06 | 0.0024
27 | ABCB1 | ATP-binding cassette, sub-family B (MDR/TAP), member 1 | 1157641 | 9 | 8 | 9 | 0 | 0 | 0 | 4 | 3 | 2 | 0 | 0.000071 | 0.084 | 0.0039 | 0.15 | 0.0047 | 5.27e-06 | 0.0035
28 | MADCAM1 | mucosal vascular addressin cell adhesion molecule 1 | 158333 | 4 | 4 | 2 | 0 | 0 | 0 | 0 | 4 | 0 | 0 | 0.00021 | 0.35 | 0.00028 | 0.99 | 0.002 | 6.75e-06 | 0.0044
29 | WDR52 | WD repeat domain 52 | 887493 | 10 | 9 | 6 | 1 | 1 | 1 | 0 | 8 | 0 | 0 | 4.37e-06 | 0.35 | 1 | 0.077 | 0.16 | 0.000011 | 0.0067
30 | TPTE2 | transmembrane phosphoinositide 3-phosphatase and tensin homolog 2 | 483148 | 8 | 7 | 8 | 1 | 1 | 0 | 0 | 6 | 1 | 0 | 1.82e-06 | 0.49 | 0.44 | 0.57 | 0.63 | 0.000017 | 0.010
31 | OR5H1 | olfactory receptor, family 5, subfamily H, member 1 | 276592 | 5 | 4 | 3 | 1 | 0 | 2 | 1 | 0 | 2 | 0 | 0.00039 | 0.49 | 0.00088 | 0.55 | 0.0032 | 0.000018 | 0.011
32 | POLDIP2 | polymerase (DNA-directed), delta interacting protein 2 | 257573 | 4 | 4 | 3 | 0 | 0 | 0 | 1 | 0 | 3 | 0 | 0.000012 | 0.66 | 0.073 | 0.99 | 0.11 | 0.000019 | 0.011
33 | PCDHGA8 | protocadherin gamma subfamily A, 8 | 835388 | 4 | 4 | 2 | 1 | 1 | 0 | 0 | 3 | 0 | 0 | 0.045 | 0.61 | 0.000026 | 0.084 | 3e-05 | 0.000019 | 0.011
34 | CCNB2 | cyclin B2 | 353170 | 5 | 5 | 5 | 0 | 0 | 0 | 2 | 1 | 2 | 0 | 0.000011 | 0.22 | 0.23 | 0.15 | 0.15 | 0.000024 | 0.013
35 | NFE2L2 | nuclear factor (erythroid-derived 2)-like 2 | 524177 | 5 | 5 | 5 | 0 | 0 | 0 | 2 | 3 | 0 | 0 | 0.00059 | 0.29 | 0.068 | 0.005 | 0.0054 | 0.000043 | 0.022

RRAD

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

SV2C

Figure S2. This figure depicts the distribution of mutations and mutation types across the SV2C significant gene.

TOR1A

Figure S3. This figure depicts the distribution of mutations and mutation types across the TOR1A significant gene.

TPST1

Figure S4. This figure depicts the distribution of mutations and mutation types across the TPST1 significant gene.

MTOR

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

EBPL

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

ANKRD36

Figure S7. This figure depicts the distribution of mutations and mutation types across the ANKRD36 significant gene.

ZCCHC3

Figure S8. This figure depicts the distribution of mutations and mutation types across the ZCCHC3 significant gene.

FAM174B

Figure S9. This figure depicts the distribution of mutations and mutation types across the FAM174B significant gene.

TSPAN19

Figure S10. This figure depicts the distribution of mutations and mutation types across the TSPAN19 significant gene.

DACH2

Figure S11. This figure depicts the distribution of mutations and mutation types across the DACH2 significant gene.

KRTAP1-1

Figure S12. This figure depicts the distribution of mutations and mutation types across the KRTAP1-1 significant gene.

CR1

Figure S13. This figure depicts the distribution of mutations and mutation types across the CR1 significant gene.

KRT1

Figure S14. This figure depicts the distribution of mutations and mutation types across the KRT1 significant gene.

ABCB1

Figure S15. This figure depicts the distribution of mutations and mutation types across the ABCB1 significant gene.

WDR52

Figure S16. This figure depicts the distribution of mutations and mutation types across the WDR52 significant gene.

TPTE2

Figure S17. This figure depicts the distribution of mutations and mutation types across the TPTE2 significant gene.

OR5H1

Figure S18. This figure depicts the distribution of mutations and mutation types across the OR5H1 significant gene.

POLDIP2

Figure S19. This figure depicts the distribution of mutations and mutation types across the POLDIP2 significant gene.

PCDHGA8

Figure S20. This figure depicts the distribution of mutations and mutation types across the PCDHGA8 significant gene.

CCNB2

Figure S21. This figure depicts the distribution of mutations and mutation types across the CCNB2 significant gene.

Note:

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: *ApG->G .

n3 - number of nonsilent mutations of type: *Np(A/C/T)->transit .

n4 - number of nonsilent mutations of type: transver .

n5 - number of nonsilent mutations of type: indel+null .

null - mutation category that includes nonsense, frameshift, splice-site mutations

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 = p-value (overall)

q = q-value, False Discovery Rate (Benjamini-Hochberg procedure)

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: 85. Number of genes displayed: 10

rank | gene | description | n | cos | n_cos | N_cos | cos_ev | p | q
--- | --- | --- | --- | --- | --- | --- | --- | --- | ---
1 | VHL | von Hippel-Lindau tumor suppressor | 150 | 537 | 150 | 157341 | 3740 | 0 | 0
2 | PIK3CA | phosphoinositide-3-kinase, catalytic, alpha polypeptide | 14 | 184 | 12 | 53912 | 3014 | 0 | 0
3 | TP53 | tumor protein p53 | 13 | 308 | 12 | 90244 | 1649 | 0 | 0
4 | PTEN | phosphatase and tensin homolog (mutated in multiple advanced cancers 1) | 16 | 728 | 16 | 213304 | 120 | 0 | 0
5 | CHEK2 | CHK2 checkpoint homolog (S. pombe) | 7 | 2 | 4 | 586 | 4 | 7.3e-14 | 6.6e-11
6 | NF1 | neurofibromin 1 (neurofibromatosis, von Recklinghausen disease, Watson disease) | 11 | 285 | 6 | 83505 | 8 | 3.6e-08 | 0.000026
7 | KRAS | v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog | 4 | 51 | 4 | 14943 | 14813 | 4.1e-08 | 0.000026
8 | ARHGAP20 | Rho GTPase activating protein 20 | 4 | 2 | 2 | 586 | 2 | 7.7e-07 | 0.00043
9 | NF2 | neurofibromin 2 (merlin) | 6 | 543 | 6 | 159099 | 36 | 1.5e-06 | 0.00076
10 | SBNO1 | strawberry notch homolog 1 (Drosophila) | 3 | 4 | 2 | 1172 | 4 | 3.1e-06 | 0.0014

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: 6. 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 | VEGFPATHWAY | Vascular endothelial growth factor (VEGF) is upregulated by hypoxic conditions and promotes normal blood vessel formation and angiogenesis related to tumor growth or cardiac disease. | ARNT, EIF1, EIF1A, EIF2B1, EIF2B2, EIF2B3, EIF2B4, EIF2B5, EIF2S1, EIF2S2, EIF2S3, ELAVL1, FLT1, FLT4, HIF1A, HRAS, KDR, NOS3, PIK3CA, PIK3R1, PLCG1, PRKCA, PRKCB1, PTK2, PXN, SHC1, VEGF, VHL | 25 | EIF1(1), EIF2B1(2), EIF2B2(1), EIF2B5(2), EIF2S1(1), EIF2S2(1), ELAVL1(1), FLT1(3), FLT4(4), HIF1A(3), KDR(5), NOS3(1), PIK3CA(14), PIK3R1(1), PTK2(1), PXN(2), SHC1(2), VHL(150) | 14983008 | 195 | 165 | 140 | 17 | 7 | 18 | 26 | 53 | 91 | 0 | 2.9e-06 | <1.00e-15 | <2.96e-13
2 | HIFPATHWAY | Under normal conditions, hypoxia inducible factor HIF-1 is degraded; under hypoxic conditions, it activates transcription of genes controlled by hpoxic response elements (HREs). | ARNT, ASPH, COPS5, CREB1, EDN1, EP300, EPO, HIF1A, HSPCA, JUN, LDHA, NOS3, P4HB, VEGF, VHL | 13 | ASPH(1), EP300(6), HIF1A(3), JUN(1), NOS3(1), VHL(150) | 7504580 | 162 | 151 | 108 | 8 | 2 | 15 | 18 | 39 | 88 | 0 | 9.3e-08 | <1.00e-15 | <2.96e-13
3 | HSA04120_UBIQUITIN_MEDIATED_PROTEOLYSIS | Genes involved in ubiquitin mediated proteolysis | ANAPC1, ANAPC10, ANAPC11, ANAPC2, ANAPC4, ANAPC5, ANAPC7, BTRC, CDC16, CDC20, CDC23, CDC26, CDC27, CUL1, CUL2, CUL3, FBXW11, FBXW7, FZR1, ITCH, LOC728919, RBX1, SKP1, SKP2, SMURF1, SMURF2, TCEB1, TCEB2, UBA1, UBE2C, UBE2D1, UBE2D2, UBE2D3, UBE2D4, UBE2E1, UBE2E2, UBE2E3, VHL, WWP1, WWP2 | 39 | ANAPC1(4), ANAPC11(1), ANAPC2(1), ANAPC4(2), ANAPC5(2), ANAPC7(1), CDC16(2), CDC20(1), CDC23(2), CDC27(5), CUL1(3), CUL2(1), CUL3(2), FBXW11(1), FBXW7(4), FZR1(1), SKP2(1), SMURF1(1), SMURF2(2), TCEB1(1), UBA1(1), UBE2D1(2), UBE2D2(1), UBE2D3(1), UBE2E2(1), VHL(150), WWP1(1), WWP2(1) | 17820449 | 196 | 165 | 142 | 21 | 4 | 19 | 31 | 48 | 94 | 0 | 0.000027 | 1.44e-15 | 2.96e-13
4 | SA_PTEN_PATHWAY | PTEN is a tumor suppressor that dephosphorylates the lipid messenger phosphatidylinositol triphosphate. | AKT1, AKT2, AKT3, BPNT1, GRB2, ILK, MAPK1, MAPK3, PDK1, PIK3CA, PIK3CD, PIP3-E, PTEN, PTK2B, RBL2, SHC1, SOS1 | 16 | AKT1(1), AKT2(2), AKT3(2), MAPK1(1), MAPK3(1), PDK1(1), PIK3CA(14), PIK3CD(1), PTEN(16), PTK2B(2), RBL2(3), SHC1(2), SOS1(4) | 8973555 | 50 | 45 | 49 | 5 | 3 | 5 | 19 | 14 | 9 | 0 | 0.0012 | 4.69e-07 | 0.000072
5 | SA_TRKA_RECEPTOR | The TrkA receptor binds nerve growth factor to activate MAP kinase pathways and promote cell growth. | AKT1, AKT2, AKT3, ARHA, CDKN1A, ELK1, GRB2, HRAS, MAP2K1, MAP2K2, NGFB, NGFR, NTRK1, PIK3CA, PIK3CD, SHC1, SOS1 | 15 | AKT1(1), AKT2(2), AKT3(2), CDKN1A(1), ELK1(1), MAP2K1(1), NGFR(1), NTRK1(2), PIK3CA(14), PIK3CD(1), SHC1(2), SOS1(4) | 7184719 | 32 | 31 | 31 | 2 | 2 | 3 | 13 | 13 | 1 | 0 | 0.0029 | 0.000027 | 0.0033
6 | BLYMPHOCYTEPATHWAY | B cells express the major histocompatibility complex (class II MHC), immunoglobulins, adhesion proteins, and other factors on their cell surface. | CD80, CR1, CR2, FCGR2B, HLA-DRA, HLA-DRB1, ICAM1, ITGAL, ITGB2, PTPRC, TNFRSF5 | 10 | CD80(1), CR1(11), CR2(1), HLA-DRA(1), ITGAL(3), ITGB2(1), PTPRC(6) | 6737962 | 24 | 23 | 21 | 2 | 2 | 0 | 2 | 11 | 9 | 0 | 0.091 | 0.00019 | 0.019
7 | HSA04140_REGULATION_OF_AUTOPHAGY | Genes involved in regulation of autophagy | ATG12, ATG3, ATG5, ATG7, BECN1, GABARAP, GABARAPL1, IFNA1, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA2, IFNA21, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNG, INS, LOC441925, PIK3C3, PIK3R4, PRKAA1, PRKAA2, ULK1, ULK2, ULK3 | 29 | ATG12(1), ATG3(3), ATG7(4), BECN1(1), IFNA1(1), IFNA14(1), IFNA16(1), IFNA21(1), IFNA5(1), IFNA7(1), IFNA8(1), PIK3C3(4), PIK3R4(7), PRKAA1(1), ULK1(1), ULK2(2), ULK3(2) | 9349525 | 33 | 32 | 33 | 4 | 3 | 1 | 5 | 17 | 7 | 0 | 0.077 | 0.0034 | 0.26
8 | HSA00950_ALKALOID_BIOSYNTHESIS_I | Genes involved in alkaloid biosynthesis I | DDC, GOT1, GOT2, TAT, TYR | 5 | DDC(3), GOT1(1), GOT2(3), TAT(1), TYR(1) | 2063429 | 9 | 9 | 9 | 1 | 1 | 0 | 5 | 1 | 2 | 0 | 0.21 | 0.0034 | 0.26
9 | ACETAMINOPHENPATHWAY | Acetaminophen selectively inhibits Cox-3, which is localized to the brain, and yields the toxic metabolite NAPQI when processed by CAR in the liver. | CYP1A2, CYP2E1, CYP3A, NR1I3, PTGS1, PTGS2 | 5 | CYP1A2(2), CYP2E1(2), NR1I3(1), PTGS2(4) | 2332448 | 9 | 9 | 9 | 1 | 1 | 0 | 1 | 5 | 2 | 0 | 0.35 | 0.0074 | 0.51
10 | HSA00272_CYSTEINE_METABOLISM | Genes involved in cysteine metabolism | CARS, CARS2, CDO1, CTH, GOT1, GOT2, LDHA, LDHAL6A, LDHAL6B, LDHB, LDHC, MPST, SDS, SULT1B1, SULT1C2, SULT1C4, SULT4A1 | 17 | CARS(2), CARS2(3), CTH(1), GOT1(1), GOT2(3), LDHAL6B(1), LDHB(1), LDHC(2), MPST(2), SULT1C2(1), SULT4A1(1) | 5521164 | 18 | 18 | 18 | 2 | 2 | 1 | 5 | 5 | 5 | 0 | 0.14 | 0.0083 | 0.51

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 | HSA04140_REGULATION_OF_AUTOPHAGY | Genes involved in regulation of autophagy | ATG12, ATG3, ATG5, ATG7, BECN1, GABARAP, GABARAPL1, IFNA1, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA2, IFNA21, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNG, INS, LOC441925, PIK3C3, PIK3R4, PRKAA1, PRKAA2, ULK1, ULK2, ULK3 | 29 | ATG12(1), ATG3(3), ATG7(4), BECN1(1), IFNA1(1), IFNA14(1), IFNA16(1), IFNA21(1), IFNA5(1), IFNA7(1), IFNA8(1), PIK3C3(4), PIK3R4(7), PRKAA1(1), ULK1(1), ULK2(2), ULK3(2) | 9349525 | 33 | 32 | 33 | 4 | 3 | 1 | 5 | 17 | 7 | 0 | 0.077 | 0.0034 | 1
2 | HSA00950_ALKALOID_BIOSYNTHESIS_I | Genes involved in alkaloid biosynthesis I | DDC, GOT1, GOT2, TAT, TYR | 5 | DDC(3), GOT1(1), GOT2(3), TAT(1), TYR(1) | 2063429 | 9 | 9 | 9 | 1 | 1 | 0 | 5 | 1 | 2 | 0 | 0.21 | 0.0034 | 1
3 | ACETAMINOPHENPATHWAY | Acetaminophen selectively inhibits Cox-3, which is localized to the brain, and yields the toxic metabolite NAPQI when processed by CAR in the liver. | CYP1A2, CYP2E1, CYP3A, NR1I3, PTGS1, PTGS2 | 5 | CYP1A2(2), CYP2E1(2), NR1I3(1), PTGS2(4) | 2332448 | 9 | 9 | 9 | 1 | 1 | 0 | 1 | 5 | 2 | 0 | 0.35 | 0.0074 | 1
4 | HSA00272_CYSTEINE_METABOLISM | Genes involved in cysteine metabolism | CARS, CARS2, CDO1, CTH, GOT1, GOT2, LDHA, LDHAL6A, LDHAL6B, LDHB, LDHC, MPST, SDS, SULT1B1, SULT1C2, SULT1C4, SULT4A1 | 17 | CARS(2), CARS2(3), CTH(1), GOT1(1), GOT2(3), LDHAL6B(1), LDHB(1), LDHC(2), MPST(2), SULT1C2(1), SULT4A1(1) | 5521164 | 18 | 18 | 18 | 2 | 2 | 1 | 5 | 5 | 5 | 0 | 0.14 | 0.0083 | 1
5 | CYSTEINE_METABOLISM |  | CARS, CTH, GOT1, GOT2, LDHA, LDHB, LDHC, MPST | 8 | CARS(2), CTH(1), GOT1(1), GOT2(3), LDHB(1), LDHC(2), MPST(2) | 3003190 | 12 | 12 | 12 | 2 | 2 | 0 | 4 | 3 | 3 | 0 | 0.33 | 0.013 | 1
6 | 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 | ARG1(1), CPS1(5), GLS(1), GLUD1(2), GOT1(1) | 3418789 | 10 | 10 | 10 | 1 | 0 | 0 | 6 | 2 | 2 | 0 | 0.12 | 0.017 | 1
7 | HSA00130_UBIQUINONE_BIOSYNTHESIS | Genes involved in ubiquinone biosynthesis | COQ2, COQ3, COQ5, COQ6, COQ7, ND1, ND2, ND3, ND4, ND4L, ND5, ND6, NDUFA12, NDUFA13, NDUFB11 | 8 | COQ5(2), COQ6(1), NDUFA13(3), NDUFB11(1) | 1778759 | 7 | 7 | 7 | 0 | 2 | 0 | 1 | 3 | 1 | 0 | 0.15 | 0.023 | 1
8 | TCRAPATHWAY | The kinases Lck and Fyn phosphorylate and activate the T cell receptor, which recognizes antigen-bound MHCII and leads to T cell activation. | CD3D, CD3E, CD3G, CD3Z, CD4, FYN, HLA-DRA, HLA-DRB1, LCK, PTPRC, TRA@, TRB@, ZAP70 | 10 | CD3E(1), CD3G(1), CD4(1), FYN(1), HLA-DRA(1), PTPRC(6), ZAP70(2) | 3990851 | 13 | 11 | 13 | 0 | 1 | 2 | 0 | 7 | 3 | 0 | 0.095 | 0.025 | 1
9 | HSA00401_NOVOBIOCIN_BIOSYNTHESIS | Genes involved in novobiocin biosynthesis | GOT1, GOT2, TAT | 3 | GOT1(1), GOT2(3), TAT(1) | 1153972 | 5 | 5 | 5 | 1 | 1 | 0 | 3 | 0 | 1 | 0 | 0.42 | 0.028 | 1
10 | HSA00400_PHENYLALANINE_TYROSINE_AND_TRYPTOPHAN_BIOSYNTHESIS | Genes involved in phenylalanine, tyrosine and tryptophan biosynthesis | FARS2, FARSA, FARSB, GOT1, GOT2, PAH, TAT, YARS, YARS2 | 9 | FARSA(1), FARSB(1), GOT1(1), GOT2(3), PAH(3), TAT(1), YARS(1) | 3828103 | 11 | 11 | 11 | 1 | 1 | 0 | 3 | 5 | 2 | 0 | 0.18 | 0.029 | 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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