Skin Cutaneous Melanoma: Mutation Analysis (MutSig v2.0)
(BRAF_Hotspot_Mutants 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: SKCM-BRAF_Hotspot_Mutants

- Number of patients in set: 97

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:SKCM-BRAF_Hotspot_Mutants.final_analysis_set.maf

- Significantly mutated genes (q ≤ 0.1): 58

- Mutations seen in COSMIC: 232

- Significantly mutated genes in COSMIC territory: 10

- Genes with clustered mutations (≤ 3 aa apart): 899

- Significantly mutated genesets: 2

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

Mutation Preprocessing

- Read 97 MAFs of type "Broad"

- Total number of mutations in input MAFs: 55227

- After removing 2 mutations outside chr1-24: 55225

- After removing 325 blacklisted mutations: 54900

- After removing 1075 noncoding mutations: 53825

Mutation Filtering

- Number of mutations before filtering: 53825

- After removing 723 mutations outside gene set: 53102

- After removing 32 mutations outside category set: 53070

Results
Breakdown of Mutations by Type

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

type | count
--- | ---
Frame_Shift_Del | 304
Frame_Shift_Ins | 94
In_Frame_Del | 105
In_Frame_Ins | 13
Missense_Mutation | 33009
Nonsense_Mutation | 1986
Nonstop_Mutation | 14
Silent | 16955
Splice_Site | 575
Translation_Start_Site | 15
Total | 53070

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
--- | --- | --- | --- | --- | --- | ---
(C/T)p*C->T | 23000 | 771897641 | 3e-05 | 30 | 2.3 | 1.6
(A/G)p*C->T | 2721 | 647491941 | 4.2e-06 | 4.2 | 0.32 | 1.9
A->G | 1765 | 1373132947 | 1.3e-06 | 1.3 | 0.099 | 2.3
transver | 5538 | 2792522529 | 2e-06 | 2 | 0.15 | 5
indel+null | 3060 | 2792522529 | 1.1e-06 | 1.1 | 0.085 | NaN
double_null | 31 | 2792522529 | 1.1e-08 | 0.011 | 0.00086 | NaN
Total | 36115 | 2792522529 | 0.000013 | 13 | 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: SKCM-BRAF_Hotspot_Mutants.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: (C/T)p*C->T

- n2 = number of nonsilent mutations of type: (A/G)p*C->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: 58. 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 | BRAF | v-raf murine sarcoma viral oncogene homolog B1 | 215475 | 99 | 97 | 4 | 1 | 2 | 0 | 0 | 97 | 0 | 0 | <1.00e-15 | 1.5e-07 | 0 | 0 | <1.00e-15 | <1.80e-11
2 | CDKN2A | cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) | 89548 | 12 | 12 | 10 | 0 | 4 | 0 | 0 | 0 | 8 | 0 | 3.83e-10 | 0.053 | 0.000035 | 0.000037 | 4.62e-13 | 4.17e-09
3 | PTEN | phosphatase and tensin homolog (mutated in multiple advanced cancers 1) | 108063 | 12 | 12 | 11 | 0 | 1 | 0 | 3 | 1 | 7 | 0 | 4.08e-13 | 0.089 | 0.74 | 0.26 | 3.24e-12 | 1.95e-08
4 | OR4K1 | olfactory receptor, family 4, subfamily K, member 1 | 91018 | 16 | 14 | 13 | 2 | 14 | 1 | 0 | 0 | 1 | 0 | 3.30e-10 | 0.0064 | 0.78 | 0.89 | 6.76e-09 | 2.74e-05
5 | RPTN | repetin | 229211 | 22 | 18 | 21 | 1 | 13 | 1 | 4 | 4 | 0 | 0 | 6.78e-10 | 0.011 | 0.73 | 0.49 | 7.60e-09 | 2.74e-05
6 | TP53 | tumor protein p53 | 118128 | 11 | 10 | 11 | 1 | 2 | 0 | 2 | 2 | 5 | 0 | 3.05e-08 | 0.094 | 0.064 | 0.019 | 1.27e-08 | 3.82e-05
7 | ACSM2B | acyl-CoA synthetase medium-chain family member 2B | 168684 | 20 | 16 | 17 | 2 | 16 | 0 | 0 | 2 | 2 | 0 | 1.16e-08 | 0.0046 | 0.94 | 1 | 2.24e-07 | 0.000577
8 | C7orf58 | chromosome 7 open reading frame 58 | 301090 | 16 | 13 | 15 | 1 | 10 | 1 | 1 | 0 | 4 | 0 | 7.99e-06 | 0.011 | 0.001 | 0.0036 | 5.22e-07 | 0.00118
9 | GFRAL | GDNF family receptor alpha like | 116103 | 12 | 11 | 12 | 2 | 7 | 1 | 0 | 2 | 2 | 0 | 5.58e-08 | 0.18 | 0.39 | 0.58 | 5.93e-07 | 0.00119
10 | LILRA1 | leukocyte immunoglobulin-like receptor, subfamily A (with TM domain), member 1 | 145978 | 12 | 12 | 12 | 1 | 7 | 1 | 2 | 2 | 0 | 0 | 1.35e-07 | 0.024 | 0.39 | 0.33 | 7.98e-07 | 0.00144
11 | CDK4 | cyclin-dependent kinase 4 | 91043 | 4 | 4 | 3 | 0 | 0 | 0 | 0 | 4 | 0 | 0 | 0.00337 | 0.42 | 0.032 | 0.000019 | 1.12e-06 | 0.00184
12 | DSG3 | desmoglein 3 (pemphigus vulgaris antigen) | 295650 | 20 | 17 | 18 | 1 | 18 | 2 | 0 | 0 | 0 | 0 | 4.20e-07 | 0.0042 | 0.69 | 0.4 | 2.77e-06 | 0.00416
13 | PRAMEF11 | PRAME family member 11 | 120600 | 11 | 9 | 8 | 3 | 3 | 0 | 3 | 4 | 1 | 0 | 1.89e-06 | 0.29 | 0.89 | 0.11 | 3.31e-06 | 0.00441
14 | RFX6 | regulatory factor X, 6 | 255411 | 14 | 12 | 14 | 1 | 11 | 0 | 1 | 1 | 1 | 0 | 2.06e-06 | 0.038 | 0.11 | 0.1 | 3.42e-06 | 0.00441
15 | SLC4A10 | solute carrier family 4, sodium bicarbonate transporter-like, member 10 | 266470 | 15 | 14 | 15 | 1 | 10 | 0 | 0 | 1 | 4 | 0 | 7.19e-07 | 0.029 | 0.93 | 1 | 1.09e-05 | 0.0131
16 | SERPINB4 | serpin peptidase inhibitor, clade B (ovalbumin), member 4 | 110945 | 13 | 10 | 13 | 2 | 10 | 0 | 0 | 1 | 2 | 0 | 1.28e-06 | 0.036 | 0.81 | 0.65 | 1.25e-05 | 0.0141
17 | NBPF1 | neuroblastoma breakpoint family, member 1 | 313745 | 18 | 14 | 16 | 1 | 9 | 1 | 1 | 6 | 1 | 0 | 1.56e-05 | 0.011 | 0.1 | 0.077 | 1.75e-05 | 0.0186
18 | IL32 | interleukin 32 | 48362 | 4 | 4 | 2 | 1 | 0 | 0 | 0 | 1 | 3 | 0 | 0.000187 | 0.93 | 0.86 | 0.011 | 2.90e-05 | 0.0290
19 | OR4C15 | olfactory receptor, family 4, subfamily C, member 15 | 107246 | 10 | 10 | 8 | 2 | 10 | 0 | 0 | 0 | 0 | 0 | 3.61e-06 | 0.055 | 0.75 | 0.64 | 3.20e-05 | 0.0296
20 | NELL1 | NEL-like 1 (chicken) | 232214 | 11 | 11 | 11 | 1 | 4 | 2 | 0 | 2 | 3 | 0 | 2.35e-06 | 0.1 | 0.92 | 1 | 3.28e-05 | 0.0296
21 | CDR1 | cerebellar degeneration-related protein 1, 34kDa | 76856 | 7 | 7 | 7 | 1 | 4 | 0 | 0 | 0 | 3 | 0 | 8.33e-06 | 0.26 | 0.68 | 0.35 | 4.03e-05 | 0.0346
22 | GK2 | glycerol kinase 2 | 160995 | 14 | 12 | 13 | 1 | 11 | 0 | 0 | 2 | 1 | 0 | 3.26e-06 | 0.057 | 0.58 | 1 | 4.44e-05 | 0.0365
23 | OR5D13 | olfactory receptor, family 5, subfamily D, member 13 | 90951 | 9 | 7 | 8 | 1 | 6 | 1 | 0 | 0 | 2 | 0 | 1.51e-05 | 0.034 | 0.91 | 0.26 | 5.27e-05 | 0.0412
24 | ZNF215 | zinc finger protein 215 | 152546 | 8 | 8 | 8 | 1 | 2 | 0 | 3 | 2 | 1 | 0 | 6.81e-06 | 0.2 | 0.8 | 0.6 | 5.49e-05 | 0.0412
25 | TRHR | thyrotropin-releasing hormone receptor | 115831 | 8 | 8 | 7 | 1 | 5 | 3 | 0 | 0 | 0 | 0 | 4.37e-05 | 0.045 | 0.32 | 0.13 | 7.30e-05 | 0.0488
26 | MORF4 | mortality factor 4 | 68955 | 8 | 8 | 8 | 1 | 6 | 0 | 0 | 1 | 1 | 0 | 5.65e-06 | 0.14 | 0.92 | 1 | 7.39e-05 | 0.0488
27 | PRSS1 | protease, serine, 1 (trypsin 1) | 74104 | 8 | 8 | 8 | 2 | 6 | 0 | 1 | 1 | 0 | 0 | 9.68e-06 | 0.18 | 0.64 | 0.6 | 7.55e-05 | 0.0488
28 | UNC119B | unc-119 homolog B (C. elegans) | 68908 | 4 | 4 | 4 | 1 | 1 | 0 | 0 | 3 | 0 | 0 | 0.00385 | 0.6 | 0.0017 | 0.0015 | 7.57e-05 | 0.0488
29 | RGS21 | regulator of G-protein signaling 21 | 43410 | 5 | 5 | 5 | 0 | 3 | 0 | 0 | 2 | 0 | 0 | 7.85e-05 | 0.21 | 0.63 | 0.077 | 7.85e-05 | 0.0489
30 | FUT9 | fucosyltransferase 9 (alpha (1,3) fucosyltransferase) | 99525 | 7 | 7 | 7 | 1 | 4 | 1 | 1 | 1 | 0 | 0 | 5.09e-05 | 0.22 | 0.089 | 0.13 | 8.54e-05 | 0.0514
31 | CCDC102B | coiled-coil domain containing 102B | 148571 | 9 | 9 | 7 | 1 | 7 | 1 | 0 | 0 | 1 | 0 | 8.62e-05 | 0.11 | 0.6 | 0.086 | 9.53e-05 | 0.0543
32 | ST6GAL2 | ST6 beta-galactosamide alpha-2,6-sialyltranferase 2 | 138224 | 14 | 13 | 13 | 3 | 11 | 1 | 0 | 1 | 1 | 0 | 2.22e-05 | 0.068 | 0.087 | 0.34 | 9.62e-05 | 0.0543
33 | OR11L1 | olfactory receptor, family 11, subfamily L, member 1 | 93528 | 8 | 8 | 6 | 0 | 7 | 0 | 0 | 1 | 0 | 0 | 9.29e-05 | 0.0035 | 0.71 | 0.085 | 0.000101 | 0.0550
34 | GIMAP4 | GTPase, IMAP family member 4 | 96124 | 4 | 4 | 3 | 1 | 3 | 0 | 0 | 1 | 0 | 0 | 0.0170 | 0.41 | 0.18 | 0.00052 | 0.000112 | 0.0592
35 | ICA1L | islet cell autoantigen 1,69kDa-like | 146534 | 5 | 5 | 3 | 0 | 1 | 0 | 0 | 3 | 1 | 0 | 0.0120 | 0.46 | 0.0006 | 0.00076 | 0.000115 | 0.0592

BRAF

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

CDKN2A

Figure S2. This figure depicts the distribution of mutations and mutation types across the CDKN2A significant gene.

PTEN

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

OR4K1

Figure S4. This figure depicts the distribution of mutations and mutation types across the OR4K1 significant gene.

RPTN

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

TP53

Figure S6. This figure depicts the distribution of mutations and mutation types across the TP53 significant gene.

ACSM2B

Figure S7. This figure depicts the distribution of mutations and mutation types across the ACSM2B significant gene.

C7orf58

Figure S8. This figure depicts the distribution of mutations and mutation types across the C7orf58 significant gene.

GFRAL

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

LILRA1

Figure S10. This figure depicts the distribution of mutations and mutation types across the LILRA1 significant gene.

CDK4

Figure S11. This figure depicts the distribution of mutations and mutation types across the CDK4 significant gene.

DSG3

Figure S12. This figure depicts the distribution of mutations and mutation types across the DSG3 significant gene.

PRAMEF11

Figure S13. This figure depicts the distribution of mutations and mutation types across the PRAMEF11 significant gene.

RFX6

Figure S14. This figure depicts the distribution of mutations and mutation types across the RFX6 significant gene.

SLC4A10

Figure S15. This figure depicts the distribution of mutations and mutation types across the SLC4A10 significant gene.

SERPINB4

Figure S16. This figure depicts the distribution of mutations and mutation types across the SERPINB4 significant gene.

NBPF1

Figure S17. This figure depicts the distribution of mutations and mutation types across the NBPF1 significant gene.

IL32

Figure S18. This figure depicts the distribution of mutations and mutation types across the IL32 significant gene.

OR4C15

Figure S19. This figure depicts the distribution of mutations and mutation types across the OR4C15 significant gene.

NELL1

Figure S20. This figure depicts the distribution of mutations and mutation types across the NELL1 significant gene.

CDR1

Figure S21. This figure depicts the distribution of mutations and mutation types across the CDR1 significant gene.

GK2

Figure S22. This figure depicts the distribution of mutations and mutation types across the GK2 significant gene.

OR5D13

Figure S23. This figure depicts the distribution of mutations and mutation types across the OR5D13 significant gene.

ZNF215

Figure S24. This figure depicts the distribution of mutations and mutation types across the ZNF215 significant gene.

TRHR

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

PRSS1

Figure S26. This figure depicts the distribution of mutations and mutation types across the PRSS1 significant gene.

UNC119B

Figure S27. This figure depicts the distribution of mutations and mutation types across the UNC119B significant gene.

RGS21

Figure S28. This figure depicts the distribution of mutations and mutation types across the RGS21 significant gene.

FUT9

Figure S29. This figure depicts the distribution of mutations and mutation types across the FUT9 significant gene.

CCDC102B

Figure S30. This figure depicts the distribution of mutations and mutation types across the CCDC102B significant gene.

ST6GAL2

Figure S31. This figure depicts the distribution of mutations and mutation types across the ST6GAL2 significant gene.

OR11L1

Figure S32. This figure depicts the distribution of mutations and mutation types across the OR11L1 significant gene.

GIMAP4

Figure S33. This figure depicts the distribution of mutations and mutation types across the GIMAP4 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: 10. Number of genes displayed: 10

rank | gene | description | n | cos | n_cos | N_cos | cos_ev | p | q
--- | --- | --- | --- | --- | --- | --- | --- | --- | ---
1 | BRAF | v-raf murine sarcoma viral oncogene homolog B1 | 99 | 89 | 97 | 8633 | 1393888 | 0 | 0
2 | CDKN2A | cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) | 12 | 332 | 12 | 32204 | 330 | 0 | 0
3 | TP53 | tumor protein p53 | 11 | 356 | 11 | 34532 | 638 | 1.9e-12 | 2.9e-09
4 | PTEN | phosphatase and tensin homolog (mutated in multiple advanced cancers 1) | 12 | 767 | 12 | 74399 | 308 | 5.4e-10 | 6.1e-07
5 | NAP1L2 | nucleosome assembly protein 1-like 2 | 6 | 1 | 2 | 97 | 2 | 7.8e-07 | 0.0007
6 | CAMTA1 | calmodulin binding transcription activator 1 | 8 | 2 | 2 | 194 | 2 | 3.1e-06 | 0.0018
7 | CCNA1 | cyclin A1 | 8 | 2 | 2 | 194 | 4 | 3.1e-06 | 0.0018
8 | STK19 | serine/threonine kinase 19 | 2 | 2 | 2 | 194 | 4 | 3.1e-06 | 0.0018
9 | IDH1 | isocitrate dehydrogenase 1 (NADP+), soluble | 3 | 5 | 2 | 485 | 2984 | 2e-05 | 0.0098
10 | DCLK3 | doublecortin-like kinase 3 | 5 | 6 | 2 | 582 | 2 | 0.000028 | 0.013

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
--- | --- | --- | --- | --- | --- | --- | --- | --- | --- | ---
1006 | BRAF | v-raf murine sarcoma viral oncogene homolog B1 | 99 | 0 | 3403 | 3403 | 3403 | 3403 | 3403 | 3403
10684 | TTN | titin | 291 | 0 | 11 | 14 | 30 | 11 | 14 | 30
6304 | MUC16 | mucin 16, cell surface associated | 227 | 0 | 9 | 25 | 66 | 9 | 25 | 66
2879 | DNAH5 | dynein, axonemal, heavy chain 5 | 103 | 0 | 8 | 13 | 35 | 8 | 13 | 35
7436 | PCLO | piccolo (presynaptic cytomatrix protein) | 75 | 0 | 6 | 14 | 20 | 6 | 14 | 20
7988 | PRAMEF11 | PRAME family member 11 | 11 | 0 | 6 | 10 | 10 | 6 | 10 | 10
2264 | CNTN5 | contactin 5 | 24 | 0 | 6 | 9 | 12 | 6 | 9 | 12
729 | ASXL3 | additional sex combs like 3 (Drosophila) | 28 | 0 | 6 | 7 | 11 | 6 | 7 | 11
8529 | RGS7 | regulator of G-protein signaling 7 | 13 | 0 | 6 | 7 | 7 | 6 | 7 | 7
2295 | COL21A1 | collagen, type XXI, alpha 1 | 13 | 0 | 6 | 6 | 17 | 6 | 6 | 17

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: 2. 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 | 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 | BRAF(99), CREB5(2), MAPK1(1), RAF1(3), SNX13(1) | 1602469 | 106 | 97 | 11 | 7 | 6 | 0 | 1 | 98 | 1 | 0 | 0.00014 | 1.9e-15 | 1.2e-12
2 | ST_ERK1_ERK2_MAPK_PATHWAY | The Erk1 and Erk2 MAP kinase pathways are regulated by Raf, Mos, and Tpl-2. | ARAF1, ATF1, BAD, BRAF, COPEB, CREB1, CREB3, CREB5, DUSP4, DUSP6, DUSP9, EEF2K, EIF4E, GRB2, HTATIP, MAP2K1, MAP2K2, MAP3K8, MAPK1, MAPK3, MKNK1, MKNK2, MOS, NFKB1, RAP1A, RPS6KA1, RPS6KA2, RPS6KA3, SHC1, SOS1, SOS2, TRAF3 | 29 | ATF1(3), BRAF(99), CREB5(2), DUSP6(1), GRB2(1), MAP2K1(3), MAP2K2(2), MAPK1(1), MKNK1(2), MOS(1), NFKB1(1), RPS6KA1(1), RPS6KA2(5), RPS6KA3(1), SOS1(3), SOS2(4), TRAF3(2) | 4188759 | 132 | 97 | 35 | 21 | 22 | 1 | 2 | 104 | 3 | 0 | 0.0072 | 3.7e-14 | 1.1e-11
3 | 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 | CDK4(4), CDKN1A(1), CDKN2A(12), CFL1(1), E2F2(1), MDM2(2), PRB1(7), TP53(11) | 1208404 | 39 | 27 | 35 | 5 | 13 | 1 | 2 | 10 | 13 | 0 | 0.0074 | 0.0013 | 0.27
4 | SA_REG_CASCADE_OF_CYCLIN_EXPR | Expression of cyclins regulates progression through the cell cycle by activating cyclin-dependent kinases. | CCNA1, CCNA2, CCND1, CCNE1, CCNE2, CDK2, CDK4, CDKN1B, CDKN2A, E2F1, E2F2, E2F4, PRB1 | 13 | CCNA1(8), CCNE1(1), CCNE2(5), CDK4(4), CDKN2A(12), E2F2(1), PRB1(7) | 1286870 | 38 | 28 | 34 | 5 | 19 | 0 | 1 | 10 | 8 | 0 | 0.0088 | 0.0028 | 0.43
5 | HSA04150_MTOR_SIGNALING_PATHWAY | Genes involved in mTOR signaling pathway | AKT1, AKT2, AKT3, BRAF, CAB39, DDIT4, EIF4B, EIF4EBP1, FIGF, FRAP1, GBL, HIF1A, IGF1, INS, KIAA1303, LYK5, MAPK1, MAPK3, PDPK1, PGF, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PRKAA1, PRKAA2, RHEB, RICTOR, RPS6, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KA6, RPS6KB1, RPS6KB2, STK11, TSC1, TSC2, ULK1, ULK2, ULK3, VEGFA, VEGFB, VEGFC | 44 | AKT1(3), AKT2(2), AKT3(1), BRAF(99), FIGF(2), HIF1A(3), IGF1(5), MAPK1(1), PDPK1(1), PIK3CA(3), PIK3CB(9), PIK3CD(3), PIK3CG(8), PIK3R1(3), PIK3R2(3), PIK3R5(7), PRKAA2(6), RICTOR(2), RPS6KA1(1), RPS6KA2(5), RPS6KA3(1), RPS6KA6(7), STK11(2), TSC1(1), TSC2(3), ULK1(1), ULK2(3), ULK3(1), VEGFA(2), VEGFB(1), VEGFC(6) | 7494768 | 195 | 97 | 99 | 34 | 51 | 3 | 4 | 125 | 11 | 1 | 0.000081 | 0.021 | 1
6 | ST_DIFFERENTIATION_PATHWAY_IN_PC12_CELLS | Rat-derived PC12 cells respond to nerve growth factor (NGF) and PACAP to differentiate into neuronal cells. | AKT1, ASAH1, ATF1, BRAF, CAMP, CREB1, CREB3, CREB5, CREBBP, CRKL, DAG1, EGR1, EGR2, EGR3, EGR4, ELK1, FRS2, GAS, GNAQ, GRF2, JUN, MAP1B, MAP2K4, MAP2K7, MAPK1, MAPK10, MAPK3, MAPK8, MAPK8IP1, MAPK8IP2, MAPK8IP3, MAPK9, NTRK1, OPN1LW, PACAP, PIK3C2G, PIK3CA, PIK3CD, PIK3R1, PTPN11, RPS6KA3, SH2B, SHC1, SRC, TERF2IP, TH, TUBA3 | 42 | AKT1(3), ATF1(3), BRAF(99), CREB5(2), CREBBP(4), CRKL(1), DAG1(1), EGR2(2), EGR4(1), ELK1(1), FRS2(1), GNAQ(1), JUN(1), MAP1B(5), MAP2K4(1), MAP2K7(1), MAPK1(1), MAPK10(2), MAPK8IP1(1), MAPK8IP2(1), MAPK9(1), NTRK1(5), OPN1LW(1), PIK3C2G(10), PIK3CA(3), PIK3CD(3), PIK3R1(3), PTPN11(2), RPS6KA3(1), TH(4) | 7267574 | 165 | 97 | 70 | 30 | 40 | 5 | 2 | 113 | 4 | 1 | 0.00077 | 0.021 | 1
7 | IL5PATHWAY | Pro-inflammatory IL-5 is secretes by activated T cells, eosinophils, and mast cells, and stimulates the proliferation and activation of eosinophils in bone marrow. | CCL11, CCR3, CD4, HLA-DRA, HLA-DRB1, IL1B, IL4, IL5, IL5RA, IL6 | 10 | CCL11(1), CCR3(5), CD4(5), HLA-DRA(3), HLA-DRB1(1), IL1B(2), IL5(1), IL5RA(3) | 761782 | 21 | 19 | 20 | 4 | 15 | 1 | 0 | 4 | 1 | 0 | 0.01 | 0.03 | 1
8 | STEROID_BIOSYNTHESIS |  | CYP17A1, F13B, HSD17B1, HSD17B2, HSD17B3, HSD17B4, HSD17B7, HSD3B1, HSD3B2 | 9 | CYP17A1(2), F13B(7), HSD17B2(3), HSD17B4(4), HSD3B1(3), HSD3B2(3) | 1145924 | 22 | 20 | 21 | 3 | 16 | 0 | 2 | 2 | 1 | 1 | 0.007 | 0.034 | 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(3), DCN(7), KERA(2), LUM(4) | 506483 | 16 | 13 | 16 | 4 | 11 | 2 | 0 | 0 | 3 | 0 | 0.032 | 0.06 | 1
10 | BBCELLPATHWAY | Fas ligand expression by T cells induces apoptosis in Fas-expressing, inactive B cells. | CD28, CD4, HLA-DRA, HLA-DRB1, TNFRSF5, TNFRSF6, TNFSF5, TNFSF6 | 4 | CD4(5), HLA-DRA(3), HLA-DRB1(1) | 334543 | 9 | 8 | 9 | 0 | 5 | 1 | 0 | 3 | 0 | 0 | 0.019 | 0.077 | 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 | IL5PATHWAY | Pro-inflammatory IL-5 is secretes by activated T cells, eosinophils, and mast cells, and stimulates the proliferation and activation of eosinophils in bone marrow. | CCL11, CCR3, CD4, HLA-DRA, HLA-DRB1, IL1B, IL4, IL5, IL5RA, IL6 | 10 | CCL11(1), CCR3(5), CD4(5), HLA-DRA(3), HLA-DRB1(1), IL1B(2), IL5(1), IL5RA(3) | 761782 | 21 | 19 | 20 | 4 | 15 | 1 | 0 | 4 | 1 | 0 | 0.01 | 0.03 | 1
2 | STEROID_BIOSYNTHESIS |  | CYP17A1, F13B, HSD17B1, HSD17B2, HSD17B3, HSD17B4, HSD17B7, HSD3B1, HSD3B2 | 9 | CYP17A1(2), F13B(7), HSD17B2(3), HSD17B4(4), HSD3B1(3), HSD3B2(3) | 1145924 | 22 | 20 | 21 | 3 | 16 | 0 | 2 | 2 | 1 | 1 | 0.007 | 0.034 | 1
3 | SLRPPATHWAY | Small leucine-rich proteoglycans (SLRPs) interact with and reorganize collagen fibers in the extracellular matrix. | BGN, DCN, DSPG3, FMOD, KERA, LUM | 5 | BGN(3), DCN(7), KERA(2), LUM(4) | 506483 | 16 | 13 | 16 | 4 | 11 | 2 | 0 | 0 | 3 | 0 | 0.032 | 0.06 | 1
4 | BBCELLPATHWAY | Fas ligand expression by T cells induces apoptosis in Fas-expressing, inactive B cells. | CD28, CD4, HLA-DRA, HLA-DRB1, TNFRSF5, TNFRSF6, TNFSF5, TNFSF6 | 4 | CD4(5), HLA-DRA(3), HLA-DRB1(1) | 334543 | 9 | 8 | 9 | 0 | 5 | 1 | 0 | 3 | 0 | 0 | 0.019 | 0.077 | 1
5 | FOSBPATHWAY | FOSB gene expression and drug abuse | CDK5, FOSB, GRIA2, JUND, PPP1R1B | 5 | CDK5(1), FOSB(2), GRIA2(14) | 526332 | 17 | 13 | 17 | 4 | 12 | 2 | 1 | 1 | 1 | 0 | 0.087 | 0.079 | 1
6 | HSA00950_ALKALOID_BIOSYNTHESIS_I | Genes involved in alkaloid biosynthesis I | DDC, GOT1, GOT2, TAT, TYR | 5 | DDC(4), GOT1(3), GOT2(1), TAT(4), TYR(4) | 673736 | 16 | 13 | 16 | 3 | 10 | 2 | 1 | 1 | 2 | 0 | 0.059 | 0.11 | 1
7 | ASBCELLPATHWAY | B cells require interaction with helper T cells to produce antigen-specific immunoglobulins as a key element of the human immune response. | CD28, CD4, CD80, HLA-DRA, HLA-DRB1, IL10, IL2, IL4, TNFRSF5, TNFRSF6, TNFSF5, TNFSF6 | 8 | CD4(5), CD80(3), HLA-DRA(3), HLA-DRB1(1), IL10(1) | 562026 | 13 | 9 | 13 | 1 | 5 | 1 | 1 | 6 | 0 | 0 | 0.036 | 0.13 | 1
8 | 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 | 7 | AKT1(3), PIK3CA(3), PIK3R1(3), PLCB1(16), PLCG1(6), PRKCA(2), VAV1(5) | 1832035 | 38 | 28 | 38 | 6 | 24 | 1 | 2 | 6 | 4 | 1 | 0.0026 | 0.14 | 1
9 | HSA00472_D_ARGININE_AND_D_ORNITHINE_METABOLISM | Genes involved in D-arginine and D-ornithine metabolism | DAO | 1 | DAO(3) | 102790 | 3 | 3 | 3 | 1 | 2 | 0 | 1 | 0 | 0 | 0 | 0.54 | 0.16 | 1
10 | HSA00550_PEPTIDOGLYCAN_BIOSYNTHESIS | Genes involved in peptidoglycan biosynthesis | GLUL, PGLYRP2 | 2 | GLUL(2), PGLYRP2(8) | 260514 | 10 | 6 | 10 | 2 | 6 | 1 | 1 | 2 | 0 | 0 | 0.16 | 0.18 | 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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