Mutation Analysis (MutSig v2.0)
Lung Adenocarcinoma (MOLECULAR_NONSMOKER)
07 February 2013  |  awg_luad__2013_02_07
Maintainer Information
Citation Information
Maintained by Dan DiCara (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Mutation Analysis (MutSig v2.0). Broad Institute of MIT and Harvard. doi:10.7908/C1SB43VM
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: MOLECULAR_NONSMOKER

  • Number of patients in set: 50

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:MOLECULAR_NONSMOKER.final_analysis_set.maf

  • Significantly mutated genes (q ≤ 0.1): 11

  • Mutations seen in COSMIC: 75

  • Significantly mutated genes in COSMIC territory: 11

  • Genes with clustered mutations (≤ 3 aa apart): 21

  • Significantly mutated genesets: 32

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

Mutation Preprocessing
  • Read 50 MAFs of type "Broad"

  • Total number of mutations in input MAFs: 15943

  • After removing 3 mutations outside chr1-24: 15940

  • After removing 217 blacklisted mutations: 15723

  • After removing 8240 noncoding mutations: 7483

  • After collapsing adjacent/redundant mutations: 6362

Mutation Filtering
  • Number of mutations before filtering: 6362

  • After removing 71 mutations outside gene set: 6291

  • After removing 3 mutations outside category set: 6288

Results
Breakdown of Mutations by Type

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

type count
Frame_Shift_Del 100
Frame_Shift_Ins 52
In_Frame_Del 36
In_Frame_Ins 6
Missense_Mutation 4048
Nonsense_Mutation 304
Nonstop_Mutation 5
Silent 1616
Splice_Site 116
Translation_Start_Site 5
Total 6288
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->mut 912 82813800 0.000011 11 3.5 2.5
Tp*Cp(A/C/T)->mut 1295 179865450 7.2e-06 7.2 2.3 3.3
(A/C/G)p*Cp(A/C/T)->mut 1079 498848200 2.2e-06 2.2 0.69 3.3
A->mut 767 732518300 1e-06 1 0.33 3.9
indel+null 616 1494045750 4.1e-07 0.41 0.13 NaN
double_null 3 1494045750 2e-09 0.002 0.00064 NaN
Total 4672 1494045750 3.1e-06 3.1 1 3.5
Target Coverage for Each Individual

The x axis represents the samples. The y axis represents the exons, one row per exon, and they are sorted by average coverage across samples. For exons with exactly the same average coverage, they are sorted next by the %GC of the exon. (The secondary sort is especially useful for the zero-coverage exons at the bottom).

Figure 1. 

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

Figure 2.  Patients counts and rates file used to generate this plot: MOLECULAR_NONSMOKER.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: *CpG->mut

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

  • n3 = number of nonsilent mutations of type: (A/C/G)p*Cp(A/C/T)->mut

  • n4 = number of nonsilent mutations of type: A->mut

  • 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: 11. 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 TP53 tumor protein p53 62900 19 17 17 0 2 2 2 2 11 0 1.1e-14 0.017 NaN NaN 1.1e-14 2e-10
2 EGFR epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian) 200450 12 10 7 0 0 0 2 6 4 0 1e-11 0.2 NaN NaN 1e-11 9.1e-08
3 CDKN2A cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) 49350 5 5 5 0 0 0 1 1 3 0 5.4e-08 0.51 NaN NaN 5.4e-08 0.00033
4 SMAD4 SMAD family member 4 85150 5 5 5 0 2 1 0 0 2 0 1.6e-07 0.31 NaN NaN 1.6e-07 0.00072
5 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 35350 4 4 2 0 0 0 4 0 0 0 3.7e-07 0.54 NaN NaN 3.7e-07 0.0013
6 KEAP1 kelch-like ECH-associated protein 1 91450 6 6 6 0 3 1 0 1 1 0 5.9e-07 0.16 NaN NaN 5.9e-07 0.0018
7 CSMD3 CUB and Sushi multiple domains 3 573500 10 10 10 0 1 2 4 3 0 0 1e-06 0.11 NaN NaN 1e-06 0.0027
8 BRAF v-raf murine sarcoma viral oncogene homolog B1 111550 5 5 4 0 0 2 0 3 0 0 0.000018 0.29 NaN NaN 0.000018 0.041
9 SPTA1 spectrin, alpha, erythrocytic 1 (elliptocytosis 2) 373400 7 7 6 1 0 1 5 0 1 0 0.000034 0.46 NaN NaN 0.000034 0.063
10 STK11 serine/threonine kinase 11 43500 3 3 3 0 0 0 1 1 1 0 0.000035 0.44 NaN NaN 0.000035 0.063
11 OR4A5 olfactory receptor, family 4, subfamily A, member 5 47600 3 3 3 0 1 0 1 1 0 0 0.000055 0.38 NaN NaN 0.000055 0.09
12 SETD2 SET domain containing 2 319150 6 5 6 0 0 0 0 1 4 1 0.000071 0.31 NaN NaN 0.000071 0.11
13 MGAT4C mannosyl (alpha-1,3-)-glycoprotein beta-1,4-N-acetylglucosaminyltransferase, isozyme C (putative) 72450 3 3 3 0 2 0 0 1 0 0 0.000084 0.59 NaN NaN 0.000084 0.11
14 CDH10 cadherin 10, type 2 (T2-cadherin) 120550 4 4 4 0 2 0 2 0 0 0 0.000089 0.37 NaN NaN 0.000089 0.11
15 KRTAP4-11 keratin associated protein 4-11 27950 2 2 2 0 0 1 1 0 0 0 0.000093 0.58 NaN NaN 0.000093 0.11
16 U2AF2 U2 small nuclear RNA auxiliary factor 2 71100 3 3 3 0 0 0 1 1 1 0 0.00014 0.62 NaN NaN 0.00014 0.16
17 CRIPAK cysteine-rich PAK1 inhibitor 61350 3 3 2 1 1 0 0 0 2 0 0.00024 0.9 NaN NaN 0.00024 0.24
18 FAM5C family with sequence similarity 5, member C 116450 4 4 4 1 1 1 0 1 1 0 0.00026 0.7 NaN NaN 0.00026 0.24
19 GRM1 glutamate receptor, metabotropic 1 184100 5 5 5 0 2 3 0 0 0 0 0.00026 0.15 NaN NaN 0.00026 0.24
20 HSD3B1 hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1 56700 3 3 3 0 0 1 1 1 0 0 0.00029 0.42 NaN NaN 0.00029 0.26
21 OR2W5 olfactory receptor, family 2, subfamily W, member 5 48350 3 3 3 0 1 0 2 0 0 0 0.0003 0.43 NaN NaN 0.0003 0.26
22 OR2M4 olfactory receptor, family 2, subfamily M, member 4 46950 3 3 3 0 0 1 1 1 0 0 0.00034 0.41 NaN NaN 0.00034 0.28
23 FRMD8 FERM domain containing 8 51200 3 3 3 0 1 0 1 0 1 0 0.00036 0.34 NaN NaN 0.00036 0.28
24 PAK1IP1 PAK1 interacting protein 1 60950 3 3 3 0 1 1 0 0 1 0 0.00038 0.37 NaN NaN 0.00038 0.28
25 OR2C3 olfactory receptor, family 2, subfamily C, member 3 48350 3 3 3 0 0 2 1 0 0 0 0.00039 0.22 NaN NaN 0.00039 0.28
26 ASCL3 achaete-scute complex homolog 3 (Drosophila) 27500 2 2 2 0 0 0 0 1 1 0 0.00043 0.63 NaN NaN 0.00043 0.29
27 FMO3 flavin containing monooxygenase 3 81550 3 3 3 0 0 0 0 3 0 0 0.00043 0.53 NaN NaN 0.00043 0.29
28 PBX2 pre-B-cell leukemia homeobox 2 59050 3 3 3 0 1 0 1 0 1 0 0.00045 0.53 NaN NaN 0.00045 0.29
29 MET met proto-oncogene (hepatocyte growth factor receptor) 215350 4 4 4 0 0 0 0 1 3 0 0.00048 0.51 NaN NaN 0.00048 0.29
30 SKIV2L2 superkiller viralicidic activity 2-like 2 (S. cerevisiae) 161850 4 4 4 1 1 1 1 0 1 0 0.00048 0.8 NaN NaN 0.00048 0.29
31 G3BP1 GTPase activating protein (SH3 domain) binding protein 1 72250 3 3 3 0 0 0 2 1 0 0 0.00053 0.51 NaN NaN 0.00053 0.31
32 CST5 cystatin D 22050 2 2 2 0 0 1 0 1 0 0 0.00057 0.56 NaN NaN 0.00057 0.32
33 CTNNB1 catenin (cadherin-associated protein), beta 1, 88kDa 120100 3 3 3 0 0 2 0 1 0 0 0.0007 0.48 NaN NaN 0.0007 0.36
34 DCAF4L2 DDB1 and CUL4 associated factor 4-like 2 59600 3 3 3 0 1 1 0 1 0 0 0.0007 0.4 NaN NaN 0.0007 0.36
35 DNAJB7 DnaJ (Hsp40) homolog, subfamily B, member 7 46700 2 2 2 0 2 0 0 0 0 0 0.00072 0.66 NaN NaN 0.00072 0.36
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 TP53 tumor protein p53 19 356 18 17800 2191 0 0
2 EGFR epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian) 12 293 12 14650 5627 0 0
3 BRAF v-raf murine sarcoma viral oncogene homolog B1 5 89 5 4450 28829 4.2e-12 6.3e-09
4 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 4 52 4 2600 57936 1.8e-10 2e-07
5 CDKN2A cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) 5 332 5 16600 93 3e-09 2.7e-06
6 SMAD4 SMAD family member 4 5 159 4 7950 17 1.6e-08 0.000012
7 MET met proto-oncogene (hepatocyte growth factor receptor) 4 34 3 1700 9 2.5e-08 0.000016
8 CTNNB1 catenin (cadherin-associated protein), beta 1, 88kDa 3 138 3 6900 1551 1.6e-06 0.00093
9 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 3 220 3 11000 1965 6.6e-06 0.0033
10 APOBEC3G apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3G 1 1 1 50 1 0.00016 0.064

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
958 EGFR epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian) 12 0 10 10 10 10 10 10
1667 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 4 0 6 6 6 6 6 6
3278 TP53 tumor protein p53 19 0 2 6 22 2 6 22
3040 SPTA1 spectrin, alpha, erythrocytic 1 (elliptocytosis 2) 7 0 1 2 2 1 2 2
303 BRAF v-raf murine sarcoma viral oncogene homolog B1 5 0 1 1 3 1 1 3
485 CBWD1 COBW domain containing 1 2 0 1 1 1 1 1 1
2971 SMAD4 SMAD family member 4 5 0 1 1 1 1 1 1
3116 TACC2 transforming, acidic coiled-coil containing protein 2 2 0 1 1 1 1 1 1
262 BAIAP3 BAI1-associated protein 3 2 1 0 1 1 0 1 1
476 CARM1 coactivator-associated arginine methyltransferase 1 2 1 0 1 1 0 1 1

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: 32. 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 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 CCND1(1), CDK4(1), CDKN2A(5), TP53(19) 646050 26 18 24 1 4 2 3 3 14 0 0.016 <1.00e-15 <6.16e-13
2 RNAPATHWAY dsRNA-activated protein kinase phosphorylates elF2a, which generally inhibits translation, and activates NF-kB to provoke inflammation. CHUK, DNAJC3, EIF2S1, EIF2S2, MAP3K14, NFKB1, NFKBIA, PRKR, RELA, TP53 9 NFKB1(2), TP53(19) 736450 21 18 19 1 3 2 3 2 11 0 0.05 2.34e-14 7.22e-12
3 PLK3PATHWAY Active Plk3 phosphorylates CDC25c, blocking the G2/M transition, and phosphorylates p53 to induce apoptosis. ATM, ATR, CDC25C, CHEK1, CHEK2, CNK, TP53, YWHAH 7 ATM(2), ATR(2), TP53(19) 1204700 23 19 21 1 3 4 2 3 11 0 0.058 1.17e-12 2.15e-10
4 RBPATHWAY The ATM protein kinase recognizes DNA damage and blocks cell cycle progression by phosphorylating chk1 and p53, which normally inhibits Rb to allow G1/S transitions. ATM, CDC2, CDC25A, CDC25B, CDC25C, CDK2, CDK4, CHEK1, MYT1, RB1, TP53, WEE1, YWHAH 12 ATM(2), CDK4(1), RB1(1), TP53(19) 1325400 23 20 21 1 4 2 2 3 12 0 0.038 1.39e-12 2.15e-10
5 TERTPATHWAY hTERC, the RNA subunit of telomerase, and hTERT, the catalytic protein subunit, are required for telomerase activity and are overexpressed in many cancers. HDAC1, MAX, MYC, SP1, SP3, TP53, WT1, ZNF42 7 MAX(1), TP53(19) 530100 20 18 18 3 2 2 2 2 12 0 0.3 2.33e-12 2.87e-10
6 TELPATHWAY Telomerase is a ribonucleotide protein that adds telomeric repeats to the 3' ends of chromosomes. AKT1, BCL2, EGFR, G22P1, HSPCA, IGF1R, KRAS2, MYC, POLR2A, PPP2CA, PRKCA, RB1, TEP1, TERF1, TERT, TNKS, TP53, XRCC5 15 EGFR(12), IGF1R(2), POLR2A(2), PRKCA(1), RB1(1), TEP1(2), TP53(19), XRCC5(2) 2114100 41 24 34 1 2 3 8 10 18 0 0.00098 3.22e-12 3.31e-10
7 PMLPATHWAY Ring-shaped PML nuclear bodies regulate transcription and are required co-activators in p53- and DAXX-mediated apoptosis. CREBBP, DAXX, HRAS, PAX3, PML, PRAM-1, RARA, RB1, SIRT1, SP100, TNF, TNFRSF1A, TNFRSF1B, TNFRSF6, TNFSF6, TP53, UBL1 13 CREBBP(2), RARA(1), RB1(1), SP100(1), TP53(19) 1445900 24 20 22 0 2 2 4 3 13 0 0.0032 1.31e-11 1.15e-09
8 TIDPATHWAY On ligand binding, interferon gamma receptors stimulate JAK2 kinase to phosphorylate STAT transcription factors, which promote expression of interferon responsive genes. DNAJA3, HSPA1A, IFNG, IFNGR1, IFNGR2, IKBKB, JAK2, LIN7A, NFKB1, NFKBIA, RB1, RELA, TIP-1, TNF, TNFRSF1A, TNFRSF1B, TP53, USH1C, WT1 18 IKBKB(1), NFKB1(2), RB1(1), TP53(19) 1382600 23 20 21 1 3 3 3 2 12 0 0.022 1.72e-11 1.32e-09
9 P53HYPOXIAPATHWAY Hypoxia induces p53 accumulation and consequent apoptosis with p53-mediated cell cycle arrest, which is present under conditions of DNA damage. ABCB1, AKT1, ATM, BAX, CDKN1A, CPB2, CSNK1A1, CSNK1D, FHL2, GADD45A, HIC1, HIF1A, HSPA1A, HSPCA, IGFBP3, MAPK8, MDM2, NFKBIB, NQO1, TP53 19 ATM(2), BAX(1), MAPK8(1), TP53(19) 1566000 23 19 21 1 3 3 3 3 11 0 0.035 2.31e-10 1.58e-08
10 P53PATHWAY p53 induces cell cycle arrest or apoptosis under conditions of DNA damage. APAF1, ATM, BAX, BCL2, CCND1, CCNE1, CDK2, CDK4, CDKN1A, E2F1, GADD45A, MDM2, PCNA, RB1, TIMP3, TP53 16 ATM(2), BAX(1), CCND1(1), CDK4(1), RB1(1), TP53(19) 1368250 25 21 23 3 5 2 3 3 12 0 0.14 7.70e-10 4.75e-08

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 NFATPATHWAY Cardiac hypertrophy is induced by NF-ATc4 and GATA4, which are stimulated through calcineurin activated by CaMK. ACTA1, AGT, AKT1, CALM1, CALM2, CALM3, CALR, CAMK1, CAMK1G, CAMK4, CREBBP, CSNK1A1, CTF1, DTR, EDN1, ELSPBP1, F2, FGF2, FKBP1A, GATA4, GSK3B, HAND1, HAND2, HRAS, IGF1, LIF, MAP2K1, MAPK1, MAPK14, MAPK3, MAPK8, MEF2C, MYH2, NFATC1, NFATC2, NFATC3, NFATC4, NKX2-5, NPPA, PIK3CA, PIK3R1, PPP3CA, PPP3CB, PPP3CC, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, RAF1, RPS6KB1, SYT1 51 CAMK1(1), CAMK4(1), CREBBP(2), IGF1(1), LIF(1), MAPK8(1), MYH2(1), NFATC2(1), NFATC3(1), NFATC4(1), NKX2-5(1), NPPA(1), PIK3CA(3), PPP3CA(2), PPP3CB(1), PPP3CC(1) 3808800 20 20 20 1 1 8 6 2 3 0 0.034 0.00044 0.27
2 CK1PATHWAY Caseine kinase 1 (CK1) and cdk5 phosphorylate DARPP32 in the dopamine signaling pathway. CDK5, CDK5R1, CSNK1D, DRD1, DRD2, GRM1, PLCB1, PPP1CA, PPP1R1B, PPP2CA, PPP3CA, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B 17 DRD2(2), GRM1(5), PPP1R1B(1), PPP3CA(2) 1211600 10 9 10 0 2 3 3 2 0 0 0.058 0.0046 1
3 GSK3PATHWAY Bacterial lipopolysaccharide activates AKT to promote the survival and activation of macrophages and inhibits Gsk3-beta to promote beta-catenin accumulation in the nucleus. AKT1, APC, AXIN1, CCND1, CD14, CTNNB1, DVL1, FZD1, GJA1, GNAI1, GSK3B, IRAK1, LBP, LEF1, LY96, MYD88, NFKB1, PDPK1, PIK3CA, PIK3R1, PPP2CA, PRKR, RELA, TIRAP, TLR4, TOLLIP, WNT1 26 APC(1), CCND1(1), CD14(1), CTNNB1(3), LEF1(1), MYD88(1), NFKB1(2), PIK3CA(3), TLR4(3) 2310000 16 12 16 1 4 5 2 4 1 0 0.076 0.015 1
4 UREACYCLEPATHWAY Ammonia released from amino acid deamination is used to produce carbamoyl phosphate, which is used to convert ornithine to citrulline, from which urea is eventually formed. ARG1, ASL, ASS, CPS1, GLS, GLUD1, GOT1 6 ASL(1), CPS1(3), GOT1(1) 584650 5 5 5 1 1 1 2 0 1 0 0.59 0.017 1
5 RANKLPATHWAY RANK is a TNF-type receptor that promotes osteoclast differentiation and consequent bone resorbtion on binding RANK ligand produced by osteoblasts. FOS, FOSL1, FOSL2, IFNAR1, IFNAR2, IFNB1, ISGF3G, MAPK8, NFKB1, PRKR, RELA, TNFRSF11A, TNFSF11, TRAF6 12 FOSL1(1), MAPK8(1), NFKB1(2), TNFRSF11A(2), TRAF6(1) 834150 7 6 7 0 2 2 2 0 1 0 0.13 0.018 1
6 FLUMAZENILPATHWAY Flumazenil is a benzodiazepine receptor antagonist that may induce protective preconditioning in ischemic cardiomyocytes. GABRA1, GABRA2, GABRA3, GABRA4, GABRA5, GABRA6, GPX1, PRKCE, SOD1 9 GABRA1(1), GABRA2(2), GABRA5(1), PRKCE(1) 596250 5 5 5 1 1 0 1 2 1 0 0.58 0.019 1
7 TOLLPATHWAY Toll-like receptors are activated by bacterial lipoproteins, lipopolysaccharides, and other surface molecules, and activate pro-inflammatory factors such as NF-kB. CD14, CHUK, ELK1, FOS, IKBKB, IKBKG, IRAK1, JUN, LY96, MAP2K3, MAP2K4, MAP2K6, MAP3K1, MAP3K14, MAP3K7, MAP3K7IP1, MAP3K7IP2, MAPK14, MAPK8, MYD88, NFKB1, NFKBIA, PGLYRP, PPARA, PRKR, RELA, SITPEC, TIRAP, TLR10, TLR2, TLR3, TLR4, TLR6, TLR7, TLR9, TOLLIP, TRAF6 31 CD14(1), IKBKB(1), MAP2K3(1), MAP3K1(1), MAP3K7(1), MAPK8(1), MYD88(1), NFKB1(2), TLR4(3), TLR6(1), TLR7(3), TRAF6(1) 2736100 17 14 17 2 3 3 7 3 1 0 0.17 0.023 1
8 TOB1PATHWAY TGF-beta signaling activates SMADs, which interact with intracellular Tob to maintain unstimulated T cells by repressing IL-2 expression. CD28, CD3D, CD3E, CD3G, CD3Z, IFNG, IL2, IL2RA, IL4, MADH3, MADH4, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2, TGFBR3, TOB1, TOB2, TRA@, TRB@ 16 TGFBR1(1), TGFBR3(2), TOB1(1), TOB2(1) 796550 5 5 5 1 0 2 1 0 2 0 0.64 0.029 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 ARPC2(1), ARPC3(1), CDC42(1), PDGFRA(1), PIK3CA(3) 1004800 7 7 7 0 1 5 0 1 0 0 0.18 0.031 1
10 RIBOFLAVIN_METABOLISM ACP1, ACP2, ACP5, ACPP, ACPT, ENPP1, ENPP3, FLAD1, RFK, TYR 10 ACP1(1), ACP2(1), ENPP1(1), ENPP3(1), TYR(1) 729400 5 5 5 1 0 1 1 1 2 0 0.6 0.032 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. ##REF##99

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.

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