Mutation Analysis (MutSig v2.0)
Testicular Germ Cell Tumors (Primary solid tumor)
21 August 2015  |  analyses__2015_08_21
Maintainer Information
Citation Information
doi:10.7908/C1DR2TSC
Maintained by David Heiman (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2015): Mutation Analysis (MutSig v2.0). Broad Institute of MIT and Harvard. doi:10.7908/C1DR2TSC
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: TGCT-TP

  • Number of patients in set: 149

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:TGCT-TP.final_analysis_set.maf

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

  • Significantly mutated genes (q ≤ 0.1): 48

  • Mutations seen in COSMIC: 77

  • Significantly mutated genes in COSMIC territory: 11

  • Significantly mutated genesets: 3

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

Mutation Preprocessing

  • Read 149 MAFs of type "maf1"

  • Total number of mutations in input MAFs: 14126

  • After removing 55 mutations outside chr1-24: 14071

  • After removing 470 blacklisted mutations: 13601

  • After removing 2387 noncoding mutations: 11214

  • After collapsing adjacent/redundant mutations: 11213

Mutation Filtering

  • Number of mutations before filtering: 11213

  • After removing 873 mutations outside gene set: 10340

  • After removing 8 mutations outside category set: 10332

Results
Breakdown of Mutations by Type

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

type count
De_novo_Start_InFrame 4
De_novo_Start_OutOfFrame 5
Frame_Shift_Del 175
Frame_Shift_Ins 90
In_Frame_Del 89
In_Frame_Ins 22
Missense_Mutation 6563
Nonsense_Mutation 433
Nonstop_Mutation 4
Silent 2607
Splice_Site 329
Start_Codon_SNP 11
Total 10332
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->(A/T) 1525 277176689 5.5e-06 5.5 3.4 2.1
*Cp(A/C/T)->(A/T) 3331 2192395219 1.5e-06 1.5 0.95 2.7
A->(C/G) 1037 2336356068 4.4e-07 0.44 0.28 3.4
flip 681 4805927976 1.4e-07 0.14 0.088 5.3
indel+null 1144 4805927976 2.4e-07 0.24 0.15 NaN
double_null 7 4805927976 1.5e-09 0.0015 0.00091 NaN
Total 7725 4805927976 1.6e-06 1.6 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: TGCT-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->(A/T)

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

  • n3 = number of nonsilent mutations of type: A->(C/G)

  • n4 = number of nonsilent mutations of type: flip

  • 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: 48. 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_clust p_cons p_joint p q
1 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 105343 19 19 7 0 0 8 3 8 0 0 2.6e-15 0.029 0.00054 0.00041 0.000037 0.000 0.000
2 KIT v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog 449194 27 26 13 0 0 5 8 11 3 0 5.3e-15 0.0034 0 0 0 <1.00e-15 <4.67e-12
3 FAM104B family with sequence similarity 104, member B 48754 11 7 3 0 0 1 0 5 5 0 1e-14 0.15 0 0.4 0 <1.00e-15 <4.67e-12
4 PNPLA4 patatin-like phospholipase domain containing 4 116976 5 5 1 0 0 0 5 0 0 0 4.5e-08 0.27 0 0.042 0 <1.00e-15 <4.67e-12
5 NRAS neuroblastoma RAS viral (v-ras) oncogene homolog 87314 7 7 4 0 0 3 4 0 0 0 4.4e-11 0.14 0.0026 0.083 0.0038 5.01e-12 1.87e-08
6 SP8 Sp8 transcription factor 124935 6 6 1 0 6 0 0 0 0 0 7.9e-07 0.052 0 0.98 2.2e-06 4.88e-11 1.52e-07
7 TPTE2 transmembrane phosphoinositide 3-phosphatase and tensin homolog 2 242626 5 5 1 2 0 0 0 0 5 0 6.4e-06 0.75 1.4e-06 0.99 2.4e-06 3.95e-10 9.37e-07
8 MUC6 mucin 6, oligomeric mucus/gel-forming 1077081 15 15 11 3 1 9 1 4 0 0 2.4e-07 0.23 9.6e-06 0.95 0.000064 4.02e-10 9.37e-07
9 MUC4 mucin 4, cell surface associated 539634 27 20 25 5 2 15 5 5 0 0 1.8e-09 0.12 NaN NaN NaN 1.75e-09 3.63e-06
10 ERC1 ELKS/RAB6-interacting/CAST family member 1 509509 7 7 3 0 1 0 5 1 0 0 1.3e-06 0.17 0.00072 0.0048 0.000069 2.08e-09 3.88e-06
11 ATXN3 ataxin 3 168326 4 4 1 0 0 0 0 0 4 0 0.000015 1 6e-07 1 0.000037 1.27e-08 2.15e-05
12 PCMTD1 protein-L-isoaspartate (D-aspartate) O-methyltransferase domain containing 1 162374 6 5 5 0 0 4 2 0 0 0 2.1e-06 0.24 0.00044 0.97 0.0005 2.29e-08 3.57e-05
13 CSGALNACT2 chondroitin sulfate N-acetylgalactosaminyltransferase 2 246792 5 5 2 0 0 2 0 0 3 0 9.9e-06 0.27 0.00011 0.57 0.00015 3.21e-08 4.49e-05
14 FANK1 fibronectin type III and ankyrin repeat domains 1 159300 4 4 1 0 0 0 0 0 4 0 0.000016 0.34 0.000025 1 0.000097 3.37e-08 4.49e-05
15 NBPF10 neuroblastoma breakpoint family, member 10 911116 7 7 2 0 0 0 0 7 0 0 9.8e-06 0.36 0.00022 1 0.00057 1.12e-07 0.000139
16 PSMD11 proteasome (prosome, macropain) 26S subunit, non-ATPase, 11 196820 4 4 1 0 4 0 0 0 0 0 0.000026 0.21 0.00011 0.66 0.00029 1.52e-07 0.000177
17 KRTAP1-1 keratin associated protein 1-1 80162 3 3 1 0 0 0 3 0 0 0 0.000012 0.51 0.0001 0.88 0.00085 1.91e-07 0.000210
18 RHPN2 rhophilin, Rho GTPase binding protein 2 294827 6 6 3 1 1 5 0 0 0 0 9.8e-06 0.26 0.0047 0.016 0.0011 2.14e-07 0.000211
19 DEK DEK oncogene (DNA binding) 174028 5 5 2 0 0 1 0 4 0 0 1.5e-06 0.5 0.0039 1 0.0075 2.15e-07 0.000211
20 SP4 Sp4 transcription factor 354431 4 4 1 0 0 4 0 0 0 0 0.0016 0.47 1.2e-06 0.94 1e-05 2.93e-07 0.000274
21 SPIN2A spindlin family, member 2A 116362 3 3 1 0 0 0 3 0 0 0 0.00012 0.42 0.00011 0.046 0.00032 6.65e-07 0.000591
22 DDX11 DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 11 (CHL1-like helicase homolog, S. cerevisiae) 450278 8 8 4 1 1 2 0 2 3 0 1.3e-07 0.57 0.17 0.87 0.35 8.20e-07 0.000696
23 FAM101B family with sequence similarity 101, member B 66098 4 4 3 0 0 1 2 0 1 0 8.2e-07 0.3 0.048 0.94 0.1 1.47e-06 0.00119
24 KRTAP10-10 keratin associated protein 10-10 113016 5 5 1 2 5 0 0 0 0 0 0.00032 0.6 0.000011 0.61 0.00033 1.77e-06 0.00138
25 MLLT3 myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 3 258821 4 4 2 1 0 0 0 1 3 0 0.000086 0.97 0.0005 0.93 0.0014 2.05e-06 0.00153
26 CDC27 cell division cycle 27 homolog (S. cerevisiae) 359494 6 6 4 1 0 1 1 0 4 0 1.3e-06 0.39 0.1 0.55 0.17 3.54e-06 0.00254
27 SSBP3 single stranded DNA binding protein 3 184464 3 3 1 0 0 0 3 0 0 0 0.00037 0.39 0.00017 0.75 0.00062 3.68e-06 0.00255
28 BCL11B B-cell CLL/lymphoma 11B (zinc finger protein) 251714 5 5 3 0 1 1 0 3 0 0 0.000015 0.24 0.0075 1 0.022 5.21e-06 0.00348
29 RUNX2 runt-related transcription factor 2 226399 4 4 2 2 1 0 0 3 0 0 0.0078 0.86 0.000012 0.58 0.000058 7.09e-06 0.00456
30 HSF4 heat shock transcription factor 4 184689 6 6 5 0 2 2 2 0 0 0 4.8e-07 0.15 0.77 0.9 1 7.47e-06 0.00465
31 LHCGR luteinizing hormone/choriogonadotropin receptor 304957 3 3 2 0 0 0 0 3 0 0 0.00095 0.58 0.00013 0.86 0.00063 9.21e-06 0.00554
32 RAC1 ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) 92618 4 4 3 0 0 0 1 2 1 0 1.1e-06 0.32 0.34 0.24 0.62 1.00e-05 0.00585
33 ZNF814 zinc finger protein 814 384311 5 5 2 2 0 0 4 0 1 0 0.013 0.79 0.000011 0.68 0.000065 1.29e-05 0.00731
34 ZNF680 zinc finger protein 680 244023 3 3 1 0 3 0 0 0 0 0 0.00011 0.42 0.045 0.42 0.013 2.01e-05 0.0110
35 ZNF799 zinc finger protein 799 290247 5 4 4 0 0 0 4 0 1 0 0.00036 0.29 0.0027 0.19 0.0051 2.57e-05 0.0137
KRAS

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

KIT

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

FAM104B

Figure S3.  This figure depicts the distribution of mutations and mutation types across the FAM104B significant gene.

PNPLA4

Figure S4.  This figure depicts the distribution of mutations and mutation types across the PNPLA4 significant gene.

NRAS

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

SP8

Figure S6.  This figure depicts the distribution of mutations and mutation types across the SP8 significant gene.

TPTE2

Figure S7.  This figure depicts the distribution of mutations and mutation types across the TPTE2 significant gene.

MUC6

Figure S8.  This figure depicts the distribution of mutations and mutation types across the MUC6 significant gene.

MUC4

Figure S9.  This figure depicts the distribution of mutations and mutation types across the MUC4 significant gene.

ERC1

Figure S10.  This figure depicts the distribution of mutations and mutation types across the ERC1 significant gene.

ATXN3

Figure S11.  This figure depicts the distribution of mutations and mutation types across the ATXN3 significant gene.

PCMTD1

Figure S12.  This figure depicts the distribution of mutations and mutation types across the PCMTD1 significant gene.

CSGALNACT2

Figure S13.  This figure depicts the distribution of mutations and mutation types across the CSGALNACT2 significant gene.

FANK1

Figure S14.  This figure depicts the distribution of mutations and mutation types across the FANK1 significant gene.

NBPF10

Figure S15.  This figure depicts the distribution of mutations and mutation types across the NBPF10 significant gene.

PSMD11

Figure S16.  This figure depicts the distribution of mutations and mutation types across the PSMD11 significant gene.

KRTAP1-1

Figure S17.  This figure depicts the distribution of mutations and mutation types across the KRTAP1-1 significant gene.

RHPN2

Figure S18.  This figure depicts the distribution of mutations and mutation types across the RHPN2 significant gene.

DEK

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

SP4

Figure S20.  This figure depicts the distribution of mutations and mutation types across the SP4 significant gene.

SPIN2A

Figure S21.  This figure depicts the distribution of mutations and mutation types across the SPIN2A significant gene.

DDX11

Figure S22.  This figure depicts the distribution of mutations and mutation types across the DDX11 significant gene.

FAM101B

Figure S23.  This figure depicts the distribution of mutations and mutation types across the FAM101B significant gene.

KRTAP10-10

Figure S24.  This figure depicts the distribution of mutations and mutation types across the KRTAP10-10 significant gene.

MLLT3

Figure S25.  This figure depicts the distribution of mutations and mutation types across the MLLT3 significant gene.

CDC27

Figure S26.  This figure depicts the distribution of mutations and mutation types across the CDC27 significant gene.

SSBP3

Figure S27.  This figure depicts the distribution of mutations and mutation types across the SSBP3 significant gene.

BCL11B

Figure S28.  This figure depicts the distribution of mutations and mutation types across the BCL11B significant gene.

RUNX2

Figure S29.  This figure depicts the distribution of mutations and mutation types across the RUNX2 significant gene.

HSF4

Figure S30.  This figure depicts the distribution of mutations and mutation types across the HSF4 significant gene.

LHCGR

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

RAC1

Figure S32.  This figure depicts the distribution of mutations and mutation types across the RAC1 significant gene.

ZNF814

Figure S33.  This figure depicts the distribution of mutations and mutation types across the ZNF814 significant gene.

ZNF680

Figure S34.  This figure depicts the distribution of mutations and mutation types across the ZNF680 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: 11. Number of genes displayed: 10

rank gene description n cos n_cos N_cos cos_ev p q
1 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 19 52 19 7748 117424 0 0
2 NRAS neuroblastoma RAS viral (v-ras) oncogene homolog 7 33 7 4917 7705 0 0
3 KIT v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog 27 240 27 35760 10702 0 0
4 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 3 220 3 32780 1335 0.000023 0.027
5 AVPR2 arginine vasopressin receptor 2 (nephrogenic diabetes insipidus) 1 1 1 149 0 0.00024 0.099
6 CCNL2 cyclin L2 1 1 1 149 1 0.00024 0.099
7 FAAH fatty acid amide hydrolase 1 1 1 149 1 0.00024 0.099
8 LYPLA1 lysophospholipase I 1 1 1 149 1 0.00024 0.099
9 MAP3K7 mitogen-activated protein kinase kinase kinase 7 2 1 1 149 1 0.00024 0.099
10 PTK7 PTK7 protein tyrosine kinase 7 1 1 1 149 1 0.00024 0.099

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: 3. 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 BADPATHWAY When phosphorylated, BAD is inhibited by sequestration; when non-phosphorylated, it promotes apoptosis by inactivating pro-survival BCL-XL and BCL-2. ADCY1, AKT1, BAD, BAX, BCL2, BCL2L1, CSF2RB, IGF1, IGF1R, IL3, IL3RA, KIT, KITLG, PIK3CA, PIK3R1, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, YWHAH 22 BCL2L1(1), IL3RA(1), KIT(27), PIK3CA(3), PIK3R1(1), PRKAR2B(2) 5007558 35 32 20 5 0 10 9 13 3 0 0.11 6.5e-07 0.0004
2 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), PAK1(1), PDGFRA(1), PIK3CA(3), PIK3R1(1), RAC1(4), WASL(2) 3047557 14 14 12 0 1 7 2 3 1 0 0.025 0.000094 0.029
3 NKCELLSPATHWAY Natural killer (NK) lymphocytes are inhibited by MHC and activated by surface glycoproteins on tumor or virus-infected cells, which undergo perforin-mediated lysis. B2M, HLA-A, IL18, ITGB1, KLRC1, KLRC2, KLRC3, KLRC4, KLRD1, LAT, MAP2K1, MAPK3, PAK1, PIK3CA, PIK3R1, PTK2B, PTPN6, RAC1, SYK, VAV1 20 HLA-A(1), KLRC3(1), KLRC4(1), PAK1(1), PIK3CA(3), PIK3R1(1), PTK2B(1), RAC1(4), SYK(1), VAV1(2) 4322569 16 16 14 0 2 6 3 4 1 0 0.012 0.00043 0.088
4 SALMONELLAPATHWAY Salmonella induces membrane ruffling in infected cells via bacterial proteins including SipA, SipC, and SopE, which alter actin structure. ACTA1, ACTR2, ACTR3, ARPC1A, ARPC1B, ARPC2, ARPC3, ARPC4, CDC42, RAC1, WASF1, WASL 12 ACTA1(1), ARPC1B(1), ARPC2(1), RAC1(4), WASL(2) 1876385 9 9 8 0 0 4 2 2 1 0 0.089 0.002 0.29
5 RASPATHWAY Ras activation stimulates many signaling cascades, including PI3K/AKT activation to inhibit apoptosis. AKT1, ARHA, BAD, BCL2L1, CASP9, CDC42, CHUK, ELK1, H2AFX, HRAS, MAP2K1, MAPK3, MLLT7, NFKB1, PIK3CA, PIK3R1, RAC1, RAF1, RALA, RALBP1, RALGDS, RELA, RHOA 21 BCL2L1(1), HRAS(1), PIK3CA(3), PIK3R1(1), RAC1(4), RAF1(1), RALGDS(1), RELA(1), RHOA(1) 4462015 14 14 12 1 1 5 2 3 3 0 0.075 0.0024 0.29
6 HSA04662_B_CELL_RECEPTOR_SIGNALING_PATHWAY Genes involved in B cell receptor signaling pathway AKT1, AKT2, AKT3, BCL10, BLNK, BTK, CARD11, CD19, CD22, CD72, CD79A, CD79B, CD81, CHP, CHUK, CR2, FCGR2B, FOS, GSK3B, HRAS, IFITM1, IKBKB, IKBKG, INPP5D, JUN, KRAS, LILRB3, LYN, MALT1, NFAT5, NFATC1, NFATC2, NFATC3, NFATC4, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NRAS, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PLCG2, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRKCB1, PTPN6, RAC1, RAC2, RAC3, RASGRP3, SYK, VAV1, VAV2, VAV3 63 AKT3(1), BLNK(1), BTK(1), CARD11(1), CD19(1), CD79A(1), CD79B(1), FOS(2), HRAS(1), INPP5D(1), KRAS(19), MALT1(1), NFATC2(4), NFATC4(1), NFKB2(2), NFKBIB(1), NRAS(7), PIK3CA(3), PIK3CB(2), PIK3CD(4), PIK3R1(1), PIK3R5(1), RAC1(4), SYK(1), VAV1(2), VAV3(1) 17419085 65 51 47 9 7 29 12 13 4 0 0.0042 0.0039 0.4
7 ERK5PATHWAY Signaling between a tissue and its innervating axon stimulates retrograde transport via Trk receptors, which activate Erk5, which induces transcription of anti-apoptotic factors. AKT1, CREB1, GRB2, HRAS, MAPK1, MAPK3, MAPK7, MEF2A, MEF2B, MEF2C, MEF2D, NTRK1, PIK3CA, PIK3R1, PLCG1, RPS6KA1, SHC1 17 HRAS(1), MAPK7(3), MEF2A(3), MEF2B(2), MEF2C(1), NTRK1(1), PIK3CA(3), PIK3R1(1), RPS6KA1(2) 4532448 17 17 13 2 4 10 0 1 2 0 0.059 0.011 0.86
8 HSA04664_FC_EPSILON_RI_SIGNALING_PATHWAY Genes involved in Fc epsilon RI signaling pathway AKT1, AKT2, AKT3, BTK, CSF2, FCER1A, FCER1G, FYN, GAB2, GRB2, HRAS, IL13, IL3, IL4, IL5, INPP5D, KRAS, LAT, LCP2, LYN, MAP2K1, MAP2K2, MAP2K3, MAP2K4, MAP2K6, MAP2K7, MAPK1, MAPK10, MAPK11, MAPK12, MAPK13, MAPK14, MAPK3, MAPK8, MAPK9, MS4A2, NRAS, PDK1, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, PLCG1, PLCG2, PRKCA, PRKCB1, PRKCD, PRKCE, RAC1, RAC2, RAC3, RAF1, SOS1, SOS2, SYK, TNF, VAV1, VAV2, VAV3 73 AKT3(1), BTK(1), HRAS(1), INPP5D(1), KRAS(19), LCP2(1), MAP2K2(1), MAPK10(1), MAPK11(1), NRAS(7), PIK3CA(3), PIK3CB(2), PIK3CD(4), PIK3R1(1), PIK3R5(1), PLA2G6(1), RAC1(4), RAF1(1), SOS1(3), SYK(1), VAV1(2), VAV3(1) 16388160 58 48 40 8 6 23 12 14 3 0 0.011 0.011 0.86
9 NUCLEOTIDE_METABOLISM ADSL, ADSS, DHFR, HPRT1, IMPDH1, MTHFD2, NME2, OAZ1, POLA, POLB, POLD1, POLG, PRPS2, RRM1, SAT, SRM 14 ADSL(2), ADSS(3), DHFR(1), POLB(1), POLD1(2), POLG(2) 2969192 11 11 11 1 5 5 1 0 0 0 0.09 0.013 0.9
10 SETPATHWAY Cytotoxic T cells release perforin, which to allow entry into target cells of granzyme B, which activates caspases, and granzyme A, which induces caspase-independent apoptosis. ANP32A, APEX1, CREBBP, DFFA, DFFB, GZMA, GZMB, HMGB2, NME1, PRF1, SET 11 APEX1(1), CREBBP(6), DFFB(1), SET(1) 2382845 9 9 9 0 0 7 1 0 1 0 0.082 0.017 1

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 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 13 ARPC1B(1), ARPC2(1), PAK1(1), PDGFRA(1), PIK3CA(3), PIK3R1(1), WASL(2) 2954939 10 10 9 0 1 7 1 1 0 0 0.067 0.011 1
2 NUCLEOTIDE_METABOLISM ADSL, ADSS, DHFR, HPRT1, IMPDH1, MTHFD2, NME2, OAZ1, POLA, POLB, POLD1, POLG, PRPS2, RRM1, SAT, SRM 14 ADSL(2), ADSS(3), DHFR(1), POLB(1), POLD1(2), POLG(2) 2969192 11 11 11 1 5 5 1 0 0 0 0.09 0.013 1
3 SETPATHWAY Cytotoxic T cells release perforin, which to allow entry into target cells of granzyme B, which activates caspases, and granzyme A, which induces caspase-independent apoptosis. ANP32A, APEX1, CREBBP, DFFA, DFFB, GZMA, GZMB, HMGB2, NME1, PRF1, SET 11 APEX1(1), CREBBP(6), DFFB(1), SET(1) 2382845 9 9 9 0 0 7 1 0 1 0 0.082 0.017 1
4 ERK5PATHWAY Signaling between a tissue and its innervating axon stimulates retrograde transport via Trk receptors, which activate Erk5, which induces transcription of anti-apoptotic factors. AKT1, CREB1, GRB2, HRAS, MAPK1, MAPK3, MAPK7, MEF2A, MEF2B, MEF2C, MEF2D, NTRK1, PIK3CA, PIK3R1, PLCG1, RPS6KA1, SHC1 16 HRAS(1), MAPK7(3), MEF2B(2), MEF2C(1), NTRK1(1), PIK3CA(3), PIK3R1(1), RPS6KA1(2) 4279787 14 14 12 1 1 10 0 1 2 0 0.045 0.02 1
5 NKCELLSPATHWAY Natural killer (NK) lymphocytes are inhibited by MHC and activated by surface glycoproteins on tumor or virus-infected cells, which undergo perforin-mediated lysis. B2M, HLA-A, IL18, ITGB1, KLRC1, KLRC2, KLRC3, KLRC4, KLRD1, LAT, MAP2K1, MAPK3, PAK1, PIK3CA, PIK3R1, PTK2B, PTPN6, RAC1, SYK, VAV1 19 HLA-A(1), KLRC3(1), KLRC4(1), PAK1(1), PIK3CA(3), PIK3R1(1), PTK2B(1), SYK(1), VAV1(2) 4229951 12 12 11 0 2 6 2 2 0 0 0.031 0.022 1
6 NGFPATHWAY Nerve growth factor (NGF) stimulates neural survival and proliferation via the TrkA and p75 receptors, which induce DAG and IP3 production and activate Ras. CSNK2A1, DPM2, ELK1, FOS, GRB2, HRAS, JUN, KLK2, MAP2K1, MAPK3, MAPK8, NGFB, NGFR, PIK3CA, PIK3R1, PLCG1, RAF1, SHC1, SOS1 18 CSNK2A1(1), FOS(2), HRAS(1), KLK2(1), NGFR(1), PIK3CA(3), PIK3R1(1), RAF1(1), SOS1(3) 4359991 14 13 13 1 2 7 2 2 1 0 0.088 0.022 1
7 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 AKT3(1), ILK(1), PIK3CA(3), PIK3CD(4), PTK2B(1), RBL2(1), SOS1(3) 4601358 14 12 12 1 2 5 3 2 2 0 0.1 0.027 1
8 GPCRDB_CLASS_B_SECRETIN_LIKE ADCYAP1R1, CALCR, CALCRL, CD97, CRHR1, CRHR2, ELTD1, EMR1, EMR2, GCGR, GHRHR, GIPR, GLP1R, GLP2R, GPR64, LPHN1, LPHN2, LPHN3, PTHR1, PTHR2, SCTR, VIPR1, VIPR2 20 CD97(4), CRHR1(1), EMR1(3), GPR64(1), LPHN1(3), LPHN2(2), LPHN3(1), VIPR1(1) 6416433 16 16 16 1 3 7 2 3 1 0 0.032 0.03 1
9 BILE_ACID_BIOSYNTHESIS ACAA1, ACAA2, ADH1A, ADH1A, ADH1B, ADH1C, ADH1B, ADH1C, ADH4, ADH6, ADH7, ADHFE1, AKR1C4, AKR1D1, ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, ALDH2, ALDH3A1, ALDH3A2, ALDH9A1, BAAT, CEL, CYP27A1, CYP7A1, HADHB, SOAT2, SRD5A1, SRD5A2 27 ADH1B(1), ADH4(1), AKR1C4(1), ALDH1A1(1), ALDH1B1(1), ALDH3A1(2), BAAT(2), CEL(3), CYP7A1(2), SOAT2(1) 5259287 15 14 15 1 4 10 0 1 0 0 0.035 0.031 1
10 IFNAPATHWAY Interferon alpha, active in the immune response, binds to the IFN receptor and activates Jak1 and Tyk2, which phosphorylate Stat1 and Stat2. IFNA1, IFNAR1, IFNAR2, IFNB1, ISGF3G, JAK1, STAT1, STAT2, TYK2 8 IFNAR1(1), IFNAR2(1), JAK1(1), STAT1(2), TYK2(3) 2481181 8 8 8 0 1 5 1 0 1 0 0.098 0.031 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.

References
[1] TCGA, Integrated genomic analyses of ovarian carcinoma, Nature 474:609 - 615 (2011)
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