Mutation Analysis (MutSig v1.5)
Uveal Melanoma (Primary solid tumor)
02 April 2015 | analyses__2015_04_02
Maintainer Information
Citation Information
doi:10.7908/C1KH0MG7
Maintained by David Heiman (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2015): Mutation Analysis (MutSig v1.5). Broad Institute of MIT and Harvard. doi:10.7908/C1KH0MG7
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 v1.5 was used to generate the results found in this report.

- Working with individual set: UVM-TP

- Number of patients in set: 80

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:UVM-TP.final_analysis_set.maf

- Blacklist used for this analysis: pancan_mutation_blacklist.v14.hg19.txt

- Significantly mutated genes (q ≤ 0.1): 9

- Mutations seen in COSMIC: 43

- Significantly mutated genes in COSMIC territory: 3

- Significantly mutated genesets: 38

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

Mutation Preprocessing

- Read 80 MAFs of type "Broad"

- Total number of mutations in input MAFs: 2528

- After removing 271 blacklisted mutations: 2257

- After removing 152 noncoding mutations: 2105

Mutation Filtering

- Number of mutations before filtering: 2105

- After removing 139 mutations outside gene set: 1966

Results
Breakdown of Mutations by Type

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

type | count
--- | ---
Frame_Shift_Del | 78
Frame_Shift_Ins | 22
In_Frame_Del | 25
In_Frame_Ins | 2
Missense_Mutation | 1246
Nonsense_Mutation | 72
Nonstop_Mutation | 1
Silent | 464
Splice_Site | 49
Translation_Start_Site | 7
Total | 1966

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 | 574 | 121008619 | 4.7e-06 | 4.7 | 7.1 | 2.1
*Cp(A/C/T)->T | 190 | 1019738599 | 1.9e-07 | 0.19 | 0.28 | 1.7
A->G | 143 | 1112999983 | 1.3e-07 | 0.13 | 0.19 | 2.3
transver | 346 | 2253747201 | 1.5e-07 | 0.15 | 0.23 | 5.1
indel+null | 249 | 2253747201 | 1.1e-07 | 0.11 | 0.17 | NaN
double_null | 0 | 2253747201 | 0 | 0 | 0 | NaN
Total | 1502 | 2253747201 | 6.7e-07 | 0.67 | 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). If the figure is unpopulated, then full coverage is assumed (e.g. MutSig CV doesn't use WIGs and assumes full coverage).

Figure 1.

Distribution of Mutation Counts, Coverage, and Mutation Rates Across Samples

Figure 2. Patients counts and rates file used to generate this plot: UVM-TP.patients.counts_and_rates.txt

Lego Plots

The mutation spectrum is depicted in the lego plots below in which the 96 possible mutation types are subdivided into six large blocks, color-coded to reflect the base substitution type. Each large block is further subdivided into the 16 possible pairs of 5' and 3' neighbors, as listed in the 4x4 trinucleotide context legend. The height of each block corresponds to the mutation frequency for that kind of mutation (counts of mutations normalized by the base coverage in a given bin). The shape of the spectrum is a signature for dominant mutational mechanisms in different tumor types.

Figure 3. Get High-res Image SNV Mutation rate lego plot for entire set. Each bin is normalized by base coverage for that bin. Colors represent the six SNV types on the upper right. The three-base context for each mutation is labeled in the 4x4 legend on the lower right. The fractional breakdown of SNV counts is shown in the pie chart on the upper left. If this figure is blank, not enough information was provided in the MAF to generate it.

Figure 4. Get High-res Image SNV Mutation rate lego plots for 4 slices of mutation allele fraction (0<=AF<0.1, 0.1<=AF<0.25, 0.25<=AF<0.5, & 0.5<=AF) . The color code and three-base context legends are the same as the previous figure. If this figure is blank, not enough information was provided in the MAF to generate it.

CoMut Plot

Figure 5. 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_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)

Table 3. Get Full Table A Ranked List of Significantly Mutated Genes. Number of significant genes found: 9. 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_ns_s | p | q
--- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | ---
1 | EIF1AX | eukaryotic translation initiation factor 1A, X-linked | 34466 | 10 | 10 | 6 | 0 | 0 | 4 | 0 | 3 | 3 | 0 | 0.11 | <1.00e-15 | <9.96e-12
2 | SF3B1 | splicing factor 3b, subunit 1, 155kDa | 313797 | 18 | 18 | 5 | 0 | 14 | 0 | 1 | 3 | 0 | 0 | 0.012 | 1.55e-15 | 9.96e-12
3 | GNA11 | guanine nucleotide binding protein (G protein), alpha 11 (Gq class) | 77747 | 36 | 36 | 3 | 0 | 2 | 0 | 0 | 34 | 0 | 0 | 0.0013 | 1.67e-15 | 9.96e-12
4 | GNAQ | guanine nucleotide binding protein (G protein), q polypeptide | 80906 | 41 | 40 | 4 | 0 | 2 | 0 | 0 | 38 | 1 | 0 | 0.0012 | 2.44e-15 | 1.10e-11
5 | BAP1 | BRCA1 associated protein-1 (ubiquitin carboxy-terminal hydrolase) | 135417 | 16 | 16 | 16 | 0 | 0 | 0 | 2 | 2 | 12 | 0 | 0.088 | 1.37e-14 | 4.90e-11
6 | PRMT8 | protein arginine methyltransferase 8 | 92574 | 5 | 5 | 1 | 0 | 0 | 0 | 5 | 0 | 0 | 0 | 0.33 | 7.21e-11 | 2.16e-07
7 | TRDN | triadin | 57437 | 3 | 3 | 1 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 1 | 1.80e-06 | 0.00463
8 | CYSLTR2 | cysteinyl leukotriene receptor 2 | 83578 | 3 | 3 | 1 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 0.58 | 7.00e-06 | 0.0157
9 | TMEM216 | transmembrane protein 216 | 25145 | 2 | 2 | 1 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0.65 | 2.43e-05 | 0.0484
10 | EIF1B | eukaryotic translation initiation factor 1B | 28613 | 2 | 2 | 2 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0.86 | 6.09e-05 | 0.109
11 | PLCB2 | phospholipase C, beta 2 | 246300 | 3 | 3 | 3 | 0 | 1 | 0 | 0 | 0 | 2 | 0 | 0.55 | 8.21e-05 | 0.134
12 | LILRB5 | leukocyte immunoglobulin-like receptor, subfamily B (with TM and ITIM domains), member 5 | 135712 | 2 | 2 | 1 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0.58 | 0.000110 | 0.165
13 | MAPKAPK5 | mitogen-activated protein kinase-activated protein kinase 5 | 80593 | 2 | 2 | 2 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 1 | 0.000192 | 0.265
14 | RPTN | repetin | 189040 | 2 | 2 | 2 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0.46 | 0.000211 | 0.270
15 | KRTAP5-2 | keratin associated protein 5-2 | 43040 | 1 | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0.6 | 0.000255 | 0.294
16 | MUC4 | mucin 4, cell surface associated | 217349 | 3 | 3 | 3 | 0 | 1 | 1 | 1 | 0 | 0 | 0 | 0.28 | 0.000276 | 0.294
17 | GMEB2 | glucocorticoid modulatory element binding protein 2 | 98241 | 2 | 2 | 2 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0.67 | 0.000278 | 0.294
18 | HSD17B7 | hydroxysteroid (17-beta) dehydrogenase 7 | 82585 | 2 | 2 | 2 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0.52 | 0.000336 | 0.335
19 | FCGR2A | Fc fragment of IgG, low affinity IIa, receptor (CD32) | 78529 | 2 | 2 | 2 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0.7 | 0.000382 | 0.356
20 | OR7D4 | olfactory receptor, family 7, subfamily D, member 4 | 75440 | 2 | 2 | 2 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0.61 | 0.000397 | 0.356
21 | MC2R | melanocortin 2 receptor (adrenocorticotropic hormone) | 71805 | 2 | 2 | 2 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0.4 | 0.000524 | 0.447
22 | PLEKHF2 | pleckstrin homology domain containing, family F (with FYVE domain) member 2 | 60320 | 1 | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0.9 | 0.000548 | 0.447
23 | IYD | iodotyrosine deiodinase | 70883 | 2 | 2 | 2 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0.5 | 0.000621 | 0.479
24 | COL14A1 | collagen, type XIV, alpha 1 | 445955 | 3 | 3 | 3 | 0 | 1 | 1 | 1 | 0 | 0 | 0 | 0.3 | 0.000647 | 0.479
25 | GNB1 | guanine nucleotide binding protein (G protein), beta polypeptide 1 | 79580 | 2 | 2 | 2 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0.55 | 0.000701 | 0.479
26 | ETS1 | v-ets erythroblastosis virus E26 oncogene homolog 1 (avian) | 120731 | 2 | 2 | 2 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0.49 | 0.000712 | 0.479
27 | CSNK1A1L | casein kinase 1, alpha 1-like | 81434 | 2 | 2 | 2 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0.45 | 0.000721 | 0.479
28 | USP49 | ubiquitin specific peptidase 49 | 148283 | 2 | 2 | 2 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0.58 | 0.000790 | 0.502
29 | ABR | active BCR-related gene | 189731 | 2 | 2 | 2 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0.5 | 0.000811 | 0.502
30 | TBX6 | T-box 6 | 78281 | 2 | 2 | 2 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0.57 | 0.000966 | 0.578
31 | KCNH5 | potassium voltage-gated channel, subfamily H (eag-related), member 5 | 242314 | 2 | 2 | 2 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0.48 | 0.00105 | 0.608
32 | TYRP1 | tyrosinase-related protein 1 | 129450 | 2 | 2 | 2 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 1 | 0.00110 | 0.617
33 | NRK | Nik related kinase | 189480 | 2 | 2 | 2 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 1 | 0.00114 | 0.617
34 | OR1L1 | olfactory receptor, family 1, subfamily L, member 1 | 74800 | 1 | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0.75 | 0.00121 | 0.625
35 | TMEM39A | transmembrane protein 39A | 113093 | 2 | 2 | 2 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0.69 | 0.00124 | 0.625

EIF1AX

Figure S1. This figure depicts the distribution of mutations and mutation types across the EIF1AX significant gene.

SF3B1

Figure S2. This figure depicts the distribution of mutations and mutation types across the SF3B1 significant gene.

GNA11

Figure S3. This figure depicts the distribution of mutations and mutation types across the GNA11 significant gene.

GNAQ

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

BAP1

Figure S5. This figure depicts the distribution of mutations and mutation types across the BAP1 significant gene.

PRMT8

Figure S6. This figure depicts the distribution of mutations and mutation types across the PRMT8 significant gene.

TRDN

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

CYSLTR2

Figure S8. This figure depicts the distribution of mutations and mutation types across the CYSLTR2 significant gene.

TMEM216

Figure S9. This figure depicts the distribution of mutations and mutation types across the TMEM216 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 | GNAQ | guanine nucleotide binding protein (G protein), q polypeptide | 41 | 4 | 37 | 320 | 3811 | 5.6e-15 | 2.5e-11
2 | RAB38 | RAB38, member RAS oncogene family | 1 | 1 | 1 | 80 | 1 | 0.000053 | 0.08
3 | RGAG4 | retrotransposon gag domain containing 4 | 2 | 1 | 1 | 80 | 1 | 0.000053 | 0.08
4 | GNA11 | guanine nucleotide binding protein (G protein), alpha 11 (Gq class) | 36 | 2 | 1 | 160 | 1 | 0.00011 | 0.12
5 | RET | ret proto-oncogene | 1 | 49 | 1 | 3920 | 1 | 0.0026 | 1
6 | BRCA2 | breast cancer 2, early onset | 2 | 59 | 1 | 4720 | 0 | 0.0031 | 1
7 | FBXW7 | F-box and WD repeat domain containing 7 | 1 | 91 | 1 | 7280 | 31 | 0.0048 | 1
8 | CDKN2A | cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) | 1 | 332 | 1 | 26560 | 6 | 0.018 | 1
9 | A4GNT | alpha-1,4-N-acetylglucosaminyltransferase | 0 | 0 | 0 | 0 | 0 | 1 | 1
10 | AACS | acetoacetyl-CoA synthetase | 0 | 0 | 0 | 0 | 0 | 1 | 1

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)

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: 38. 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 | HSA04020_CALCIUM_SIGNALING_PATHWAY | Genes involved in calcium signaling pathway | ADCY1, ADCY2, ADCY3, ADCY4, ADCY7, ADCY8, ADCY9, ADORA2A, ADORA2B, ADRA1A, ADRA1B, ADRA1D, ADRB1, ADRB2, ADRB3, AGTR1, ATP2A1, ATP2A2, ATP2A3, ATP2B1, ATP2B2, ATP2B3, ATP2B4, AVPR1A, AVPR1B, BDKRB1, BDKRB2, BST1, CACNA1A, CACNA1B, CACNA1C, CACNA1D, CACNA1E, CACNA1F, CACNA1G, CACNA1H, CACNA1I, CACNA1S, CALM1, CALM2, CALM3, CALML3, CALML6, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CAMK4, CCKAR, CCKBR, CD38, CHP, CHRM1, CHRM2, CHRM3, CHRM5, CHRNA7, CYSLTR1, CYSLTR2, DRD1, EDNRA, EDNRB, EGFR, ERBB2, ERBB3, ERBB4, F2R, GNA11, GNA14, GNA15, GNAL, GNAQ, GNAS, GRIN1, GRIN2A, GRIN2C, GRIN2D, GRM1, GRM5, GRPR, HRH1, HRH2, HTR2A, HTR2B, HTR2C, HTR4, HTR5A, HTR6, HTR7, ITPKA, ITPKB, ITPR1, ITPR2, ITPR3, LHCGR, LTB4R2, MLCK, MYLK, MYLK2, NOS1, NOS2A, NOS3, NTSR1, OXTR, P2RX1, P2RX2, P2RX3, P2RX4, P2RX5, P2RX7, P2RXL1, PDE1A, PDE1B, PDE1C, PDGFRA, PDGFRB, PHKA1, PHKA2, PHKB, PHKG1, PHKG2, PLCB1, PLCB2, PLCB3, PLCB4, PLCD1, PLCD3, PLCD4, PLCE1, PLCG1, PLCG2, PLCZ1, PLN, PPID, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRKACA, PRKACB, PRKACG, PRKCA, PRKCB1, PRKCG, PRKX, PRKY, PTAFR, PTGER1, PTGER3, PTGFR, PTK2B, RYR1, RYR2, RYR3, SLC25A4, SLC25A5, SLC25A6, SLC8A1, SLC8A2, SLC8A3, SPHK1, SPHK2, TACR1, TACR2, TACR3, TBXA2R, TNNC1, TNNC2, TRHR, TRPC1, VDAC1, VDAC2, VDAC3 | 167 | ADCY4(1), ATP2A3(1), CACNA1A(1), CACNA1B(2), CACNA1C(1), CACNA1D(2), CHRM1(1), CYSLTR2(3), ERBB4(1), GNA11(36), GNAQ(41), GRIN2A(1), HTR2B(1), ITPKB(1), ITPR1(1), P2RX3(1), PDGFRA(1), PHKA2(1), PLCB2(3), PLCB4(3), PLCD4(1), PLCE1(1), RYR1(1), RYR2(2), RYR3(1), SLC25A6(1) | 30452509 | 110 | 79 | 37 | 9 | 15 | 2 | 0 | 83 | 10 | 0 | 0.000055 | <1.00e-15 | <1.48e-13
2 | CCR3PATHWAY | CCR3 is a G-protein coupled receptor that recruits eosinophils to inflammation sites via chemokine ligands. | ARHA, CCL11, CCR3, CFL1, GNAQ, GNAS, GNB1, GNGT1, HRAS, LIMK1, MAP2K1, MAPK1, MAPK3, MYL2, NOX1, PIK3C2G, PLCB1, PPP1R12B, PRKCA, PRKCB1, PTK2, RAF1, ROCK2 | 21 | GNAQ(41), GNB1(2) | 2881413 | 43 | 41 | 6 | 0 | 3 | 0 | 0 | 39 | 1 | 0 | 0.00059 | <1.00e-15 | <1.48e-13
3 | 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 | GNAQ(41), MAPK8IP2(1) | 5810912 | 42 | 41 | 5 | 1 | 2 | 0 | 0 | 39 | 1 | 0 | 0.0021 | 1.33e-15 | 1.48e-13
4 | TUBBYPATHWAY | Tubby is activated by phospholipase C activity and hydrolysis of PIP2, after which it enters the nucleus and regulates transcription. | CHRM1, GNAQ, GNB1, GNGT1, HTR2C, PLCB1, TUB | 7 | CHRM1(1), GNAQ(41), GNB1(2) | 840313 | 44 | 41 | 7 | 0 | 4 | 0 | 0 | 39 | 1 | 0 | 0.00018 | 1.89e-15 | 1.48e-13
5 | ST_ADRENERGIC | Adrenergic receptors respond to epinephrine and norepinephrine signaling. | AKT1, APC, AR, ASAH1, BF, BRAF, CAMP, CCL13, CCL15, CCL16, DAG1, EGFR, GAS, GNA11, GNA15, GNAI1, GNAQ, ITPKA, ITPKB, ITPR1, ITPR2, ITPR3, KCNJ3, KCNJ5, KCNJ9, MAPK1, MAPK10, MAPK14, PHKA2, PIK3CA, PIK3CD, PIK3R1, PITX2, PTX1, PTX3, RAF1, SRC | 34 | APC(2), GNA11(36), GNAQ(41), ITPKB(1), ITPR1(1), PHKA2(1) | 6068206 | 82 | 74 | 12 | 2 | 5 | 0 | 0 | 75 | 2 | 0 | 0.000011 | 2.00e-15 | 1.48e-13
6 | HSA04540_GAP_JUNCTION | Genes involved in gap junction | ADCY1, ADCY2, ADCY3, ADCY4, ADCY5, ADCY6, ADCY7, ADCY8, ADCY9, ADRB1, CDC2, CSNK1D, DRD1, DRD2, EDG2, EGF, EGFR, GJA1, GJD2, GNA11, GNAI1, GNAI2, GNAI3, GNAQ, GNAS, GRB2, GRM1, GRM5, GUCY1A2, GUCY1A3, GUCY1B3, GUCY2C, GUCY2D, GUCY2F, HRAS, HTR2A, HTR2B, HTR2C, ITPR1, ITPR2, ITPR3, KRAS, LOC643224, LOC654264, MAP2K1, MAP2K2, MAP2K5, MAP3K2, MAPK1, MAPK3, MAPK7, NPR1, NPR2, NRAS, PDGFA, PDGFB, PDGFC, PDGFD, PDGFRA, PDGFRB, PLCB1, PLCB2, PLCB3, PLCB4, PRKACA, PRKACB, PRKACG, PRKCA, PRKCB1, PRKCG, PRKG1, PRKG2, PRKX, PRKY, RAF1, SOS1, SOS2, SRC, TJP1, TUBA1A, TUBA1B, TUBA1C, TUBA3C, TUBA3D, TUBA3E, TUBA4A, TUBA8, TUBAL3, TUBB, TUBB1, TUBB2A, TUBB2B, TUBB2C, TUBB3, TUBB4, TUBB4Q, TUBB6, TUBB8 | 92 | ADCY4(1), EGF(1), GJA1(1), GNA11(36), GNAQ(41), HTR2B(1), ITPR1(1), PDGFRA(1), PLCB2(3), PLCB4(3), PRKG1(1) | 15229164 | 90 | 75 | 19 | 6 | 10 | 0 | 0 | 75 | 5 | 0 | 0.00017 | 2.66e-15 | 1.48e-13
7 | ST_GAQ_PATHWAY | G-alpha-q activates phospholipase C, resulting in calcium influx and increasing protein kinase C activity. | ADRBK1, AKT1, AKT2, AKT3, BF, DAG1, GNAQ, IKBKG, ITPKA, ITPKB, ITPR1, ITPR2, ITPR3, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NFKBIL1, NFKBIL2, PDK1, PHKA2, PIK3CB, PITX2, PLD1, PLD2, PLD3, VN1R1 | 26 | ADRBK1(1), GNAQ(41), ITPKB(1), ITPR1(1), PHKA2(1), PLD2(1) | 5096728 | 46 | 40 | 9 | 2 | 3 | 1 | 0 | 39 | 3 | 0 | 0.0024 | 2.89e-15 | 1.48e-13
8 | PKCPATHWAY | Gq-coupled receptors promote hydrolysis of PIP2 to DAG and IP3, which causes calcium influx and activates protein kinase C. | GNAQ, NFKB1, NFKBIA, PLCB1, PRKCA, PRKCB1, RELA | 6 | GNAQ(41) | 953131 | 41 | 40 | 4 | 0 | 2 | 0 | 0 | 38 | 1 | 0 | 0.00061 | 3.11e-15 | 1.48e-13
9 | BIOPEPTIDESPATHWAY | Extracellular signaling peptides exert biological effects via G-protein coupled receptors (GPCRs), which activate intracellular GTPases. | AGT, AGTR2, BDK, CALM1, CALM2, CALM3, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CDK5, F2, FYN, GNA11, GNAI1, GNB1, GNGT1, GRB2, HRAS, JAK2, MAP2K1, MAP2K2, MAPK1, MAPK14, MAPK3, MAPK8, MAPT, MYLK, PLCG1, PRKCA, PRKCB1, PTK2B, RAF1, SHC1, SOS1, STAT1, STAT3, STAT5A, SYT1 | 37 | GNA11(36), GNB1(2) | 4817051 | 38 | 37 | 5 | 0 | 3 | 0 | 0 | 35 | 0 | 0 | 0.00078 | 3.11e-15 | 1.48e-13
10 | HSA04916_MELANOGENESIS | Genes involved in melanogenesis | ADCY1, ADCY2, ADCY3, ADCY4, ADCY5, ADCY6, ADCY7, ADCY8, ADCY9, ASIP, CALM1, CALM2, CALM3, CALML3, CALML6, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CREB1, CREB3, CREB3L1, CREB3L2, CREB3L3, CREB3L4, CREBBP, CTNNB1, DCT, DVL1, DVL2, DVL3, EDN1, EDNRB, EP300, FZD1, FZD10, FZD2, FZD3, FZD4, FZD5, FZD6, FZD7, FZD8, FZD9, GNAI1, GNAI2, GNAI3, GNAO1, GNAQ, GNAS, GSK3B, HRAS, KIT, KITLG, KRAS, LEF1, LOC652788, MAP2K1, MAP2K2, MAPK1, MAPK3, MC1R, MITF, NRAS, PLCB1, PLCB2, PLCB3, PLCB4, POMC, PRKACA, PRKACB, PRKACG, PRKCA, PRKCB1, PRKCG, PRKX, PRKY, RAF1, TCF7, TCF7L1, TCF7L2, TYR, TYRP1, WNT1, WNT10A, WNT10B, WNT11, WNT16, WNT2, WNT2B, WNT3, WNT3A, WNT4, WNT5A, WNT5B, WNT6, WNT7A, WNT7B, WNT8A, WNT8B, WNT9A, WNT9B | 99 | ADCY4(1), DVL2(1), EDN1(1), EP300(1), GNAQ(41), PLCB2(3), PLCB4(3), TYRP1(2) | 12402692 | 53 | 45 | 15 | 3 | 7 | 0 | 1 | 40 | 5 | 0 | 0.0028 | 3.22e-15 | 1.48e-13

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 | HSA04742_TASTE_TRANSDUCTION | Genes involved in taste transduction | ACCN1, ADCY4, ADCY6, ADCY8, CACNA1A, CACNA1B, GNAS, GNAT3, GNB1, GNB3, GNG13, GNG3, GRM4, ITPR3, KCNB1, PDE1A, PLCB2, PRKACA, PRKACB, PRKACG, PRKX, PRKY, SCNN1A, SCNN1B, SCNN1G, TAS1R1, TAS1R2, TAS1R3, TAS2R1, TAS2R10, TAS2R13, TAS2R14, TAS2R16, TAS2R3, TAS2R38, TAS2R39, TAS2R4, TAS2R40, TAS2R41, TAS2R42, TAS2R43, TAS2R44, TAS2R45, TAS2R46, TAS2R48, TAS2R49, TAS2R5, TAS2R50, TAS2R60, TAS2R7, TAS2R8, TAS2R9, TRPM5 | 48 | ADCY4(1), CACNA1A(1), CACNA1B(2), GNB1(2), GNB3(1), PLCB2(3), TAS1R2(1), TRPM5(1) | 6427695 | 12 | 11 | 12 | 2 | 4 | 1 | 1 | 2 | 4 | 0 | 0.32 | 0.00077 | 0.48
2 | SA_DIACYLGLYCEROL_SIGNALING | DAG (diacylglycerol) signaling activity | ESR1, ESR2, ITPKA, PDE1A, PDE1B, PLCB1, PLCB2, PRL, TRH, VIP | 10 | ESR1(1), PLCB2(3) | 1275965 | 4 | 4 | 4 | 0 | 1 | 1 | 0 | 0 | 2 | 0 | 0.31 | 0.0026 | 0.8
3 | STEROID_BIOSYNTHESIS |  | CYP17A1, F13B, HSD17B1, HSD17B2, HSD17B3, HSD17B4, HSD17B7, HSD3B1, HSD3B2 | 9 | CYP17A1(1), HSD17B1(1), HSD17B7(2) | 949947 | 4 | 3 | 4 | 0 | 1 | 1 | 1 | 1 | 0 | 0 | 0.24 | 0.0071 | 1
4 | TUBBYPATHWAY | Tubby is activated by phospholipase C activity and hydrolysis of PIP2, after which it enters the nucleus and regulates transcription. | CHRM1, GNAQ, GNB1, GNGT1, HTR2C, PLCB1, TUB | 6 | CHRM1(1), GNB1(2) | 759407 | 3 | 3 | 3 | 0 | 2 | 0 | 0 | 1 | 0 | 0 | 0.4 | 0.012 | 1
5 | HSA00533_KERATAN_SULFATE_BIOSYNTHESIS | Genes involved in keratan sulfate biosynthesis | B3GNT1, B3GNT2, B3GNT7, B4GALT1, B4GALT2, B4GALT3, B4GALT4, CHST1, CHST2, CHST4, CHST6, FUT8, ST3GAL1, ST3GAL2, ST3GAL3, ST3GAL4 | 16 | B4GALT4(1), CHST2(1), CHST4(1), ST3GAL3(1) | 1414921 | 4 | 4 | 4 | 0 | 3 | 1 | 0 | 0 | 0 | 0 | 0.19 | 0.013 | 1
6 | 1_2_DICHLOROETHANE_DEGRADATION |  | ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1 | 8 | ALDH1A3(1), ALDH2(1), ALDH9A1(1) | 922476 | 3 | 3 | 3 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 0.33 | 0.014 | 1
7 | ASCORBATE_AND_ALDARATE_METABOLISM |  | ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1 | 8 | ALDH1A3(1), ALDH2(1), ALDH9A1(1) | 922476 | 3 | 3 | 3 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 0.33 | 0.014 | 1
8 | HSA00053_ASCORBATE_AND_ALDARATE_METABOLISM | Genes involved in ascorbate and aldarate metabolism | ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH7A1, ALDH9A1, MIOX, UGDH | 9 | ALDH1A3(1), ALDH2(1), ALDH9A1(1) | 984315 | 3 | 3 | 3 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 0.34 | 0.017 | 1
9 | CDC42RACPATHWAY | PI3 kinase stimulates cell migration by activating cdc42, which activates ARP2/3, which in turn promotes formation of new actin fibers. | ACTR2, ACTR3, ARHA, ARPC1A, ARPC1B, ARPC2, ARPC3, ARPC4, CDC42, PAK1, PDGFRA, PIK3CA, PIK3R1, RAC1, WASL | 14 | ARPC1B(1), ARPC2(1), PDGFRA(1) | 1582336 | 3 | 3 | 3 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 0.64 | 0.02 | 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(1) | 278162 | 1 | 1 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0.75 | 0.027 | 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

In addition to the links below, the full results of the analysis summarized in this report can also be downloaded programmatically using firehose_get, or interactively from either the Broad GDAC website or TCGA Data Coordination Center Portal.

- 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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