Mutation Analysis (MutSig v2.0)
Kidney Renal Papillary Cell Carcinoma (Primary solid tumor)
21 August 2015  |  analyses__2015_08_21
Maintainer Information
Citation Information
doi:10.7908/C11V5D6J
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/C11V5D6J
Overview
Introduction

This report serves to describe the mutational landscape and properties of a given individual set, as well as rank genes and genesets according to mutational significance. MutSig v2.0 was used to generate the results found in this report.

  • Working with individual set: KIRP-TP

  • Number of patients in set: 161

Input

The input for this pipeline is a set of individuals with the following files associated for each:

  1. An annotated .maf file describing the mutations called for the respective individual, and their properties.

  2. A .wig file that contains information about the coverage of the sample.

Summary

  • MAF used for this analysis:KIRP-TP.final_analysis_set.maf

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

  • Significantly mutated genes (q ≤ 0.1): 23

  • Mutations seen in COSMIC: 56

  • Significantly mutated genes in COSMIC territory: 4

  • Significantly mutated genesets: 0

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

Mutation Preprocessing

  • Read 161 MAFs of type "maf1"

  • Total number of mutations in input MAFs: 15585

  • After removing 512 blacklisted mutations: 15073

  • After removing 403 noncoding mutations: 14670

  • After collapsing adjacent/redundant mutations: 14636

Mutation Filtering

  • Number of mutations before filtering: 14636

  • After removing 901 mutations outside gene set: 13735

  • After removing 38 mutations outside category set: 13697

  • After removing 1 "impossible" mutations in

  • gene-patient-category bins of zero coverage: 12757

Results
Breakdown of Mutations by Type

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

type count
De_novo_Start_OutOfFrame 1
Frame_Shift_Del 832
Frame_Shift_Ins 297
In_Frame_Del 181
In_Frame_Ins 45
Missense_Mutation 8110
Nonsense_Mutation 439
Nonstop_Mutation 14
Silent 3151
Splice_Site 604
Start_Codon_Del 1
Start_Codon_SNP 19
Stop_Codon_Del 2
Stop_Codon_Ins 1
Total 13697
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 840 272587938 3.1e-06 3.1 1.4 2.1
*Cp(A/C/T)->T 1417 2212498207 6.4e-07 0.64 0.3 1.7
A->G 1549 2375760574 6.5e-07 0.65 0.3 2.3
transver 4322 4860846719 8.9e-07 0.89 0.41 5
indel+null 2380 4860846719 4.9e-07 0.49 0.23 NaN
double_null 37 4860846719 7.6e-09 0.0076 0.0035 NaN
Total 10545 4860846719 2.2e-06 2.2 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: KIRP-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_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: 23. 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 MUC2 mucin 2, oligomeric mucus/gel-forming 1079801 25 19 23 18 3 7 3 11 1 0 1 0.98 0 0.98 0 <1.00e-15 <3.68e-12
2 NEFH neurofilament, heavy polypeptide 200kDa 349554 14 10 6 1 0 7 0 2 5 0 1.6e-09 0.1 0 0.96 0 <1.00e-15 <3.68e-12
3 ZNF598 zinc finger protein 598 321927 10 10 1 1 0 0 10 0 0 0 8.3e-11 0.26 0 0.99 0 <1.00e-15 <3.68e-12
4 SKI v-ski sarcoma viral oncogene homolog (avian) 202848 6 6 1 1 0 0 0 6 0 0 8.5e-06 0.48 0 0.98 0 <1.00e-15 <3.68e-12
5 KCNK5 potassium channel, subfamily K, member 5 234136 3 3 3 0 0 0 0 0 3 0 0.0044 0.33 0.055 0 0 <1.00e-15 <3.68e-12
6 HNRNPM heterogeneous nuclear ribonucleoprotein M 322264 10 10 2 0 1 0 0 0 9 0 3e-10 0.12 1e-06 0.39 7.6e-06 7.78e-14 2.16e-10
7 MET met proto-oncogene (hepatocyte growth factor receptor) 690142 16 15 14 0 0 4 4 7 1 0 1.7e-11 0.012 0.00084 0.0066 0.00014 8.20e-14 2.16e-10
8 ZNF814 zinc finger protein 814 330143 14 8 8 2 0 8 1 2 3 0 2.1e-06 0.23 6e-07 0.88 0.000012 6.36e-10 1.46e-06
9 NF2 neurofibromin 2 (merlin) 274845 10 10 10 1 0 0 0 1 9 0 4.7e-10 0.47 0.21 0.94 0.37 4.06e-09 8.31e-06
10 ACTB actin, beta 180747 6 6 6 0 0 0 4 2 0 0 4.4e-07 0.39 0.32 0.72 0.44 3.20e-06 0.00589
11 SAV1 salvador homolog 1 (Drosophila) 186449 5 5 5 0 0 2 0 0 3 0 5.3e-06 0.55 0.038 0.98 0.082 6.80e-06 0.0114
12 YBX1 Y box binding protein 1 133192 3 3 2 0 0 2 0 0 1 0 0.00041 0.37 0.00071 0.69 0.0027 1.65e-05 0.0253
13 NFE2L2 nuclear factor (erythroid-derived 2)-like 2 288984 4 4 4 0 0 0 1 3 0 0 0.0026 0.39 0.0029 0.0016 0.00055 2.02e-05 0.0272
14 UBXN11 UBX domain protein 11 244452 4 3 3 1 1 0 2 0 1 0 0.0028 0.74 8e-05 0.91 0.00051 2.07e-05 0.0272
15 LGI4 leucine-rich repeat LGI family, member 4 143767 4 4 4 0 0 1 1 2 0 0 0.000067 0.28 0.26 0.013 0.025 2.36e-05 0.0290
16 BHMT betaine-homocysteine methyltransferase 201128 5 5 5 0 0 1 2 0 2 0 0.000018 0.2 0.15 0.07 0.11 2.67e-05 0.0307
17 SF3B1 splicing factor 3b, subunit 1, 155kDa 647600 9 9 9 1 1 1 2 5 0 0 3.1e-06 0.24 0.62 0.62 0.82 3.56e-05 0.0386
18 IDUA iduronidase, alpha-L- 181170 5 5 2 0 0 0 0 5 0 0 0.000069 0.36 0.026 0.99 0.047 4.44e-05 0.0437
19 TDG thymine-DNA glycosylase 202647 5 5 3 0 0 1 0 0 4 0 0.000012 0.41 0.2 0.068 0.26 4.52e-05 0.0437
20 ATP1B1 ATPase, Na+/K+ transporting, beta 1 polypeptide 150057 5 5 5 0 0 0 1 1 3 0 4.4e-06 0.61 0.81 0.32 0.8 4.84e-05 0.0437
21 CSGALNACT2 chondroitin sulfate N-acetylgalactosaminyltransferase 2 266675 5 5 2 1 1 0 0 4 0 0 0.00021 0.71 0.0085 0.62 0.018 4.99e-05 0.0437
22 CUL3 cullin 3 376822 7 5 7 0 0 1 1 2 3 0 0.00065 0.21 0.0035 1 0.0072 6.17e-05 0.0516
23 CDC27 cell division cycle 27 homolog (S. cerevisiae) 396405 5 5 5 0 1 0 2 1 1 0 0.00032 0.17 0.013 0.4 0.02 8.12e-05 0.0650
24 OR2L8 olfactory receptor, family 2, subfamily L, member 8 151700 4 4 2 1 0 1 0 0 3 0 0.000089 0.83 0.084 0.94 0.22 0.000234 0.163
25 HOXD8 homeobox D8 99500 4 4 3 0 0 0 0 2 2 0 4e-05 0.71 0.27 0.93 0.53 0.000246 0.163
26 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 197053 5 5 5 0 0 0 2 0 3 0 0.000039 0.3 0.33 0.75 0.56 0.000255 0.163
27 NACA2 nascent polypeptide-associated complex alpha subunit 2 104972 3 3 1 2 0 3 0 0 0 0 0.06 0.8 0.00023 0.99 0.00037 0.000260 0.163
28 FAT1 FAT tumor suppressor homolog 1 (Drosophila) 2217821 14 13 14 1 1 2 2 4 4 1 0.00043 0.22 0.054 0.18 0.052 0.000261 0.163
29 B3GNT6 UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 6 (core 3 synthase) 97140 3 3 2 0 0 0 1 0 2 0 0.00016 0.6 0.032 0.96 0.15 0.000265 0.163
30 CHCHD3 coiled-coil-helix-coiled-coil-helix domain containing 3 105858 4 4 4 0 0 1 0 2 1 0 0.000032 0.45 0.53 0.46 0.71 0.000266 0.163
31 KDM6A lysine (K)-specific demethylase 6A 652356 7 7 7 0 0 0 0 0 6 1 0.000078 0.43 0.24 0.56 0.34 0.000306 0.182
32 MAST4 microtubule associated serine/threonine kinase family member 4 1097366 6 6 6 1 0 1 1 3 1 0 0.028 0.57 0.00089 0.04 0.0012 0.000372 0.214
33 KRTAP1-3 keratin associated protein 1-3 81787 4 3 3 1 0 0 0 4 0 0 0.00017 0.84 0.12 0.91 0.21 0.000404 0.225
34 KLRK1 killer cell lectin-like receptor subfamily K, member 1 106633 3 3 3 0 0 1 1 0 1 0 0.0003 0.38 0.052 0.9 0.13 0.000433 0.234
35 MKL1 megakaryoblastic leukemia (translocation) 1 410567 6 6 6 1 3 1 0 1 1 0 0.00016 0.3 0.17 0.97 0.26 0.000455 0.239
MUC2

Figure S1.  This figure depicts the distribution of mutations and mutation types across the MUC2 significant gene.

NEFH

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

ZNF598

Figure S3.  This figure depicts the distribution of mutations and mutation types across the ZNF598 significant gene.

SKI

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

KCNK5

Figure S5.  This figure depicts the distribution of mutations and mutation types across the KCNK5 significant gene.

HNRNPM

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

MET

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

ZNF814

Figure S8.  This figure depicts the distribution of mutations and mutation types across the ZNF814 significant gene.

NF2

Figure S9.  This figure depicts the distribution of mutations and mutation types across the NF2 significant gene.

ACTB

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

SAV1

Figure S11.  This figure depicts the distribution of mutations and mutation types across the SAV1 significant gene.

YBX1

Figure S12.  This figure depicts the distribution of mutations and mutation types across the YBX1 significant gene.

NFE2L2

Figure S13.  This figure depicts the distribution of mutations and mutation types across the NFE2L2 significant gene.

UBXN11

Figure S14.  This figure depicts the distribution of mutations and mutation types across the UBXN11 significant gene.

LGI4

Figure S15.  This figure depicts the distribution of mutations and mutation types across the LGI4 significant gene.

BHMT

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

SF3B1

Figure S17.  This figure depicts the distribution of mutations and mutation types across the SF3B1 significant gene.

IDUA

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

TDG

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

ATP1B1

Figure S20.  This figure depicts the distribution of mutations and mutation types across the ATP1B1 significant gene.

CSGALNACT2

Figure S21.  This figure depicts the distribution of mutations and mutation types across the CSGALNACT2 significant gene.

CUL3

Figure S22.  This figure depicts the distribution of mutations and mutation types across the CUL3 significant gene.

CDC27

Figure S23.  This figure depicts the distribution of mutations and mutation types across the CDC27 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: 4. Number of genes displayed: 10

rank gene description n cos n_cos N_cos cos_ev p q
1 MET met proto-oncogene (hepatocyte growth factor receptor) 16 34 7 5474 27 1.2e-13 5.4e-10
2 NF2 neurofibromin 2 (merlin) 10 550 7 88550 39 1.6e-09 3.7e-06
3 FGFR3 fibroblast growth factor receptor 3 (achondroplasia, thanatophoric dwarfism) 6 62 3 9982 1469 1.7e-06 0.0025
4 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 5 767 5 123487 42 9.2e-06 0.01
5 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 2 52 2 8372 29208 0.00016 0.14
6 TP53 tumor protein p53 4 356 3 57316 418 0.00029 0.14
7 CDCA8 cell division cycle associated 8 1 1 1 161 1 0.00035 0.14
8 FLCN folliculin 1 1 1 161 1 0.00035 0.14
9 NKX2-1 NK2 homeobox 1 1 1 1 161 1 0.00035 0.14
10 PHF10 PHD finger protein 10 1 1 1 161 1 0.00035 0.14

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: 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 CBLPATHWAY Activated EGF receptors undergo endocytosis into clathrin-coated vesicles, where they are recycled to the membrane or ubiquitinated by Cbl. CBL, CSF1R, EGF, EGFR, GRB2, MET, PDGFRA, PRKCA, PRKCB1, SH3GLB1, SH3GLB2, SH3KBP1, SRC 12 CBL(1), CSF1R(1), EGF(1), MET(16), PDGFRA(1), SH3KBP1(2), SRC(1) 4697422 23 20 21 1 1 5 4 11 2 0 0.016 0.0011 0.66
2 MTORPATHWAY Mammalian target of rapamycin (mTOR) senses mitogenic factors and nutrients, including ATP, and induces cell proliferation. AKT1, EIF3S10, EIF4A1, EIF4A2, EIF4B, EIF4E, EIF4EBP1, EIF4G1, EIF4G2, EIF4G3, FKBP1A, FRAP1, MKNK1, PDK2, PDPK1, PIK3CA, PIK3R1, PPP2CA, PTEN, RPS6, RPS6KB1, TSC1, TSC2 21 AKT1(1), EIF4A1(1), EIF4A2(1), EIF4B(2), EIF4EBP1(1), EIF4G1(1), EIF4G2(1), EIF4G3(4), PIK3CA(2), PIK3R1(2), PTEN(5), TSC1(2), TSC2(4) 6716562 27 24 27 2 2 6 4 6 9 0 0.023 0.01 1
3 NUCLEOTIDE_GPCRS ADORA1, ADORA2A, ADORA2B, ADORA3, GPR23, LTB4R, P2RY1, P2RY2, P2RY5, P2RY6 8 ADORA2A(2), ADORA3(1), P2RY1(2), P2RY2(1), P2RY6(2) 1424191 8 8 8 0 1 1 2 4 0 0 0.094 0.01 1
4 ERBB4PATHWAY ErbB4 (aka HER4) is a receptor tyrosine kinase that binds neuregulins as well as members of the EGF family, which also target EGF receptors. ADAM17, ERBB4, NRG2, NRG3, PRKCA, PRKCB1, PSEN1 6 ADAM17(2), ERBB4(3), NRG2(1), NRG3(3) 2177146 9 9 9 0 2 1 1 4 1 0 0.085 0.022 1
5 HSA00550_PEPTIDOGLYCAN_BIOSYNTHESIS Genes involved in peptidoglycan biosynthesis GLUL, PGLYRP2 2 GLUL(2), PGLYRP2(1) 433960 3 3 3 1 1 0 1 1 0 0 0.77 0.024 1
6 KREBPATHWAY The Krebs (citric acid) cycle takes place in mitochondria, where it extracts energy in the form of electron carriers NADH and FADH2, which drive the electron transport chain. ACO2, CS, FH, IDH2, MDH1, OGDH, SDHA, SUCLA2 8 FH(2), IDH2(1), MDH1(1), OGDH(5), SDHA(2), SUCLA2(1) 2277788 12 11 12 2 0 3 0 4 5 0 0.29 0.029 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 AKT1(1), AKT2(2), AKT3(2), PIK3CA(2), PIK3CD(1), PTEN(5), RBL2(2), SOS1(3) 4925268 18 16 18 1 2 3 3 3 7 0 0.03 0.032 1
8 HSA00480_GLUTATHIONE_METABOLISM Genes involved in glutathione metabolism ANPEP, G6PD, GCLC, GCLM, GGT1, GGTL3, GGTL4, GPX1, GPX2, GPX3, GPX4, GPX5, GPX6, GPX7, GSR, GSS, GSTA1, GSTA2, GSTA3, GSTA4, GSTA5, GSTK1, GSTM1, GSTM2, GSTM3, GSTM4, GSTM5, GSTO2, GSTP1, GSTT1, GSTT2, GSTZ1, IDH1, IDH2, MGST1, MGST2, MGST3, OPLAH, TXNDC12 37 ANPEP(2), GCLC(3), GGT1(1), GSTA1(1), GSTA2(1), GSTK1(1), GSTM1(1), GSTM4(1), GSTP1(2), GSTT1(2), IDH2(1), OPLAH(3) 5431281 19 17 19 0 2 2 5 6 4 0 0.0049 0.038 1
9 RABPATHWAY Rab family GTPases regulate vesicle transport, endocytosis and exocytosis, and vesicle docking via interactions with the rabphilins. ACTA1, MEL, RAB11A, RAB1A, RAB2, RAB27A, RAB3A, RAB4A, RAB5A, RAB6A, RAB7, RAB9A 9 ACTA1(1), RAB11A(1), RAB1A(1), RAB3A(1), RAB6A(1) 1030751 5 5 5 1 0 1 1 2 1 0 0.68 0.04 1
10 ACE_INHIBITOR_PATHWAY_PHARMGKB ACE, AGT, AGTR1, AGTR2, BDKRB2, KNG1, NOS3, REN 8 ACE(3), AGT(3), AGTR2(1), KNG1(2), NOS3(1) 2443240 10 10 10 1 1 1 1 6 1 0 0.23 0.042 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 MTORPATHWAY Mammalian target of rapamycin (mTOR) senses mitogenic factors and nutrients, including ATP, and induces cell proliferation. AKT1, EIF3S10, EIF4A1, EIF4A2, EIF4B, EIF4E, EIF4EBP1, EIF4G1, EIF4G2, EIF4G3, FKBP1A, FRAP1, MKNK1, PDK2, PDPK1, PIK3CA, PIK3R1, PPP2CA, PTEN, RPS6, RPS6KB1, TSC1, TSC2 21 AKT1(1), EIF4A1(1), EIF4A2(1), EIF4B(2), EIF4EBP1(1), EIF4G1(1), EIF4G2(1), EIF4G3(4), PIK3CA(2), PIK3R1(2), PTEN(5), TSC1(2), TSC2(4) 6716562 27 24 27 2 2 6 4 6 9 0 0.023 0.01 1
2 NUCLEOTIDE_GPCRS ADORA1, ADORA2A, ADORA2B, ADORA3, GPR23, LTB4R, P2RY1, P2RY2, P2RY5, P2RY6 8 ADORA2A(2), ADORA3(1), P2RY1(2), P2RY2(1), P2RY6(2) 1424191 8 8 8 0 1 1 2 4 0 0 0.094 0.01 1
3 ERBB4PATHWAY ErbB4 (aka HER4) is a receptor tyrosine kinase that binds neuregulins as well as members of the EGF family, which also target EGF receptors. ADAM17, ERBB4, NRG2, NRG3, PRKCA, PRKCB1, PSEN1 6 ADAM17(2), ERBB4(3), NRG2(1), NRG3(3) 2177146 9 9 9 0 2 1 1 4 1 0 0.085 0.022 1
4 HSA00550_PEPTIDOGLYCAN_BIOSYNTHESIS Genes involved in peptidoglycan biosynthesis GLUL, PGLYRP2 2 GLUL(2), PGLYRP2(1) 433960 3 3 3 1 1 0 1 1 0 0 0.77 0.024 1
5 KREBPATHWAY The Krebs (citric acid) cycle takes place in mitochondria, where it extracts energy in the form of electron carriers NADH and FADH2, which drive the electron transport chain. ACO2, CS, FH, IDH2, MDH1, OGDH, SDHA, SUCLA2 8 FH(2), IDH2(1), MDH1(1), OGDH(5), SDHA(2), SUCLA2(1) 2277788 12 11 12 2 0 3 0 4 5 0 0.29 0.029 1
6 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), PIK3CA(2), PIK3CD(1), PTEN(5), RBL2(2), SOS1(3) 4925268 18 16 18 1 2 3 3 3 7 0 0.03 0.032 1
7 HSA00480_GLUTATHIONE_METABOLISM Genes involved in glutathione metabolism ANPEP, G6PD, GCLC, GCLM, GGT1, GGTL3, GGTL4, GPX1, GPX2, GPX3, GPX4, GPX5, GPX6, GPX7, GSR, GSS, GSTA1, GSTA2, GSTA3, GSTA4, GSTA5, GSTK1, GSTM1, GSTM2, GSTM3, GSTM4, GSTM5, GSTO2, GSTP1, GSTT1, GSTT2, GSTZ1, IDH1, IDH2, MGST1, MGST2, MGST3, OPLAH, TXNDC12 37 ANPEP(2), GCLC(3), GGT1(1), GSTA1(1), GSTA2(1), GSTK1(1), GSTM1(1), GSTM4(1), GSTP1(2), GSTT1(2), IDH2(1), OPLAH(3) 5431281 19 17 19 0 2 2 5 6 4 0 0.0049 0.038 1
8 RABPATHWAY Rab family GTPases regulate vesicle transport, endocytosis and exocytosis, and vesicle docking via interactions with the rabphilins. ACTA1, MEL, RAB11A, RAB1A, RAB2, RAB27A, RAB3A, RAB4A, RAB5A, RAB6A, RAB7, RAB9A 9 ACTA1(1), RAB11A(1), RAB1A(1), RAB3A(1), RAB6A(1) 1030751 5 5 5 1 0 1 1 2 1 0 0.68 0.04 1
9 ACE_INHIBITOR_PATHWAY_PHARMGKB ACE, AGT, AGTR1, AGTR2, BDKRB2, KNG1, NOS3, REN 8 ACE(3), AGT(3), AGTR2(1), KNG1(2), NOS3(1) 2443240 10 10 10 1 1 1 1 6 1 0 0.23 0.042 1
10 UBIQUINONE_BIOSYNTHESIS NDUFA1, NDUFA10, NDUFA11, NDUFA4, NDUFA5, NDUFA8, NDUFB2, NDUFB4, NDUFB5, NDUFB6, NDUFB7, NDUFS1, NDUFS2, NDUFV1, NDUFV2 15 NDUFA11(2), NDUFB2(1), NDUFB4(1), NDUFB5(2), NDUFB7(1), NDUFS1(1), NDUFV1(1) 1698697 9 9 8 2 0 0 1 2 6 0 0.75 0.042 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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