Mutation Analysis (MutSig v2.0)
Uterine Corpus Endometrioid Carcinoma (Primary solid tumor)
16 April 2014  |  analyses__2014_04_16
Maintainer Information
Citation Information
doi:10.7908/C1MW2FTH
Maintained by Dan DiCara (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2014): Mutation Analysis (MutSig v2.0). Broad Institute of MIT and Harvard. doi:10.7908/C1MW2FTH
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: UCEC-TP

  • Number of patients in set: 248

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:UCEC-TP.final_analysis_set.maf

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

  • Significantly mutated genes (q ≤ 0.1): 32

  • Mutations seen in COSMIC: 995

  • Significantly mutated genes in COSMIC territory: 44

  • Significantly mutated genesets: 68

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

Mutation Preprocessing

  • Read 248 MAFs of type "WashU"

  • Total number of mutations in input MAFs: 184861

  • After removing 118 mutations outside chr1-24: 184743

  • After removing 1172 blacklisted mutations: 183571

  • After removing 1874 noncoding mutations: 181697

  • After collapsing adjacent/redundant mutations: 181695

Mutation Filtering

  • Number of mutations before filtering: 181695

  • After removing 15833 mutations outside gene set: 165862

  • After removing 1020 mutations outside category set: 164842

  • After removing 27 "impossible" mutations in

  • gene-patient-category bins of zero coverage: 147962

Results
Breakdown of Mutations by Type

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

type count
Frame_Shift_Del 952
Frame_Shift_Ins 419
In_Frame_Del 595
In_Frame_Ins 85
Missense_Mutation 110235
Nonsense_Mutation 11503
Nonstop_Mutation 126
Silent 38390
Splice_Site 2537
Total 164842
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 37261 363920417 0.0001 100 5.6 2.2
*Cp(A/C/T)->mut 48789 3147487610 0.000016 16 0.85 3.4
A->mut 23124 3458111551 6.7e-06 6.7 0.37 3.8
*CpG->(G/A) 1045 363920417 2.9e-06 2.9 0.16 2.7
indel+null 15351 6969519578 2.2e-06 2.2 0.12 NaN
double_null 865 6969519578 1.2e-07 0.12 0.0068 NaN
Total 126435 6969519578 0.000018 18 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: UCEC-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)->mut

  • n3 = number of nonsilent mutations of type: A->mut

  • n4 = number of nonsilent mutations of type: *CpG->(G/A)

  • 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: 32. 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 FBXW7 F-box and WD repeat domain containing 7 638720 46 39 30 1 22 12 2 1 8 1 5.66e-15 0.00048 0.0005 0.0086 0.00016 0.000 0.000
2 SPOP speckle-type POZ protein 287083 23 21 18 0 5 8 6 0 4 0 9.99e-15 0.0041 0.0034 0.035 0.0013 5.55e-16 1.70e-12
3 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 306286 228 161 134 5 20 29 21 33 98 27 2.00e-15 3.7e-12 0 0.82 0 <1.00e-15 <1.70e-12
4 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 813637 172 132 76 3 31 61 68 3 9 0 4.33e-15 2.1e-11 0 0 0 <1.00e-15 <1.70e-12
5 PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (alpha) 581125 100 83 77 2 4 4 13 1 63 15 1.55e-15 0.0021 0 0.44 0 <1.00e-15 <1.70e-12
6 CTNNB1 catenin (cadherin-associated protein), beta 1, 88kDa 592248 80 74 25 7 5 61 14 0 0 0 1.11e-15 0.0034 0 0 0 <1.00e-15 <1.70e-12
7 TP53 tumor protein p53 317550 74 69 50 2 23 18 15 1 17 0 <1.00e-15 2.1e-06 0 4e-07 0 <1.00e-15 <1.70e-12
8 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 175322 53 53 11 2 1 47 4 1 0 0 2.44e-15 0.0059 0 0.00012 0 <1.00e-15 <1.70e-12
9 PPP2R1A protein phosphatase 2 (formerly 2A), regulatory subunit A , alpha isoform 434902 30 27 18 3 10 17 1 0 2 0 2.70e-14 0.0026 0 0.14 0 <1.00e-15 <1.70e-12
10 PRKAR1B protein kinase, cAMP-dependent, regulatory, type I, beta 242642 4 4 4 3 2 0 0 1 1 0 0.987 0.8 0.0051 0 0 <1.00e-15 <1.70e-12
11 CTCF CCCTC-binding factor (zinc finger protein) 547098 48 44 38 1 8 4 7 0 26 3 4.88e-15 0.00095 0.012 0.08 0.022 4.11e-15 6.34e-12
12 FGFR2 fibroblast growth factor receptor 2 (bacteria-expressed kinase, keratinocyte growth factor receptor, craniofacial dysostosis 1, Crouzon syndrome, Pfeiffer syndrome, Jackson-Weiss syndrome) 687457 34 31 19 3 3 5 13 9 3 1 6.22e-15 0.0097 0.022 0.3 0.045 1.02e-14 1.44e-11
13 P2RY11 purinergic receptor P2Y, G-protein coupled, 11 4342 7 9 9 1 1 4 0 1 1 0 4.85e-14 0.19 NaN NaN NaN 4.85e-14 6.34e-11
14 ARID1A AT rich interactive domain 1A (SWI-like) 1412380 93 83 78 5 2 7 5 1 64 14 4.33e-15 0.00015 0.97 0.79 1 1.48e-13 1.79e-10
15 CCND1 cyclin D1 154874 14 14 12 1 1 7 3 0 3 0 1.40e-10 0.083 0.0009 0.15 0.0017 7.04e-12 7.97e-09
16 CHD4 chromodomain helicase DNA binding protein 4 1452335 43 35 38 2 16 16 8 0 2 1 3.08e-11 0.0045 0.014 0.59 0.034 3.00e-11 3.18e-08
17 NFE2L2 nuclear factor (erythroid-derived 2)-like 2 446498 15 15 12 0 2 3 5 3 2 0 2.94e-08 0.018 0.000085 0.031 0.000083 6.79e-11 6.78e-08
18 SOX17 SRY (sex determining region Y)-box 17 77226 7 7 3 0 0 6 0 0 1 0 5.57e-08 0.13 0.13 0.069 0.02 2.42e-08 2.28e-05
19 FOXA2 forkhead box A2 222670 13 12 13 1 1 3 3 0 6 0 1.92e-08 0.26 0.1 0.23 0.16 6.44e-08 5.75e-05
20 FAM9A family with sequence similarity 9, member A 249932 20 14 20 1 2 12 1 0 4 1 9.74e-08 0.1 0.12 0.99 0.2 3.63e-07 0.000308
21 MAX MYC associated factor X 205913 12 11 8 0 3 3 5 0 1 0 1.46e-05 0.05 0.16 0.014 0.037 8.38e-06 0.00677
22 ING1 inhibitor of growth family, member 1 255446 13 13 10 2 4 1 0 1 7 0 0.000625 0.082 0.0014 0.063 0.0017 1.55e-05 0.0117
23 DNER delta/notch-like EGF repeat containing 485604 21 18 20 0 4 9 5 0 3 0 0.000203 0.0019 0.28 0.0024 0.0053 1.59e-05 0.0117
24 ABI1 abl-interactor 1 390369 5 4 2 5 0 5 0 0 0 0 1.000 1 8e-07 1 2.8e-06 3.86e-05 0.0273
25 NRAS neuroblastoma RAS viral (v-ras) oncogene homolog 145328 9 9 6 2 1 4 3 0 1 0 0.000351 0.48 0.08 0.015 0.014 6.36e-05 0.0432
26 ARID5B AT rich interactive domain 5B (MRF1-like) 886908 34 29 34 8 5 5 8 2 13 1 4.54e-05 0.47 0.064 0.96 0.15 8.59e-05 0.0561
27 SGK1 serum/glucocorticoid regulated kinase 1 469608 16 15 14 3 2 5 1 1 7 0 0.000251 0.52 0.39 0.0069 0.03 9.76e-05 0.0609
28 RASA1 RAS p21 protein activator (GTPase activating protein) 1 776972 30 22 28 3 5 9 4 0 11 1 0.000153 0.094 0.08 0.035 0.052 0.000100 0.0609
29 ZNF267 zinc finger protein 267 555952 22 16 19 1 10 5 3 1 3 0 1.85e-05 0.13 0.29 0.65 0.5 0.000117 0.0683
30 TPTE transmembrane phosphatase with tensin homology 431520 32 15 28 3 9 11 9 1 2 0 0.000905 0.032 0.014 0.032 0.013 0.000144 0.0793
31 CYLC1 cylicin, basic protein of sperm head cytoskeleton 1 477704 27 18 27 2 0 16 7 0 4 0 2.46e-05 0.13 0.79 0.13 0.48 0.000145 0.0793
32 DYRK1A dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A 599522 12 12 11 1 5 2 1 1 2 1 0.00589 0.22 0.0025 0.073 0.0021 0.000153 0.0812
33 UPF3B UPF3 regulator of nonsense transcripts homolog B (yeast) 370922 20 16 20 1 4 8 6 0 2 0 0.000260 0.084 0.22 0.024 0.064 0.000200 0.102
34 METTL14 methyltransferase like 14 349596 11 10 8 0 1 2 1 4 3 0 0.000357 0.13 0.026 0.88 0.048 0.000205 0.102
35 SIN3A SIN3 homolog A, transcription regulator (yeast) 966485 29 21 27 3 5 7 7 0 10 0 0.00127 0.13 0.026 0.067 0.016 0.000239 0.116
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: 44. Number of genes displayed: 10

rank gene description n cos n_cos N_cos cos_ev p q
1 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 228 767 219 190216 15125 0 0
2 PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (alpha) 100 33 39 8184 111 2.6e-13 4.1e-10
3 FGFR2 fibroblast growth factor receptor 2 (bacteria-expressed kinase, keratinocyte growth factor receptor, craniofacial dysostosis 1, Crouzon syndrome, Pfeiffer syndrome, Jackson-Weiss syndrome) 34 51 24 12648 113 3.7e-13 4.1e-10
4 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 53 52 49 12896 556649 3.8e-13 4.1e-10
5 FBXW7 F-box and WD repeat domain containing 7 46 91 29 22568 852 5.5e-13 4.1e-10
6 TP53 tumor protein p53 74 356 72 88288 24186 6.6e-13 4.1e-10
7 CTNNB1 catenin (cadherin-associated protein), beta 1, 88kDa 80 138 67 34224 23813 6.8e-13 4.1e-10
8 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 172 220 150 54560 35669 7.5e-13 4.1e-10
9 NRAS neuroblastoma RAS viral (v-ras) oncogene homolog 9 33 6 8184 6490 1.3e-08 6.3e-06
10 RB1 retinoblastoma 1 (including osteosarcoma) 26 267 11 66216 30 6.3e-08 0.000027

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: 68. 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 EIF4PATHWAY The eIF-4F complex recognizes 5' mRNA caps, recruits RNA helicases, and maintains mRNA-ribosome bridging. AKT1, EIF4A1, EIF4A2, EIF4E, EIF4EBP1, EIF4G1, EIF4G2, EIF4G3, FRAP1, GHR, IRS1, MAPK1, MAPK14, MAPK3, MKNK1, PABPC1, PDK2, PDPK1, PIK3CA, PIK3R1, PRKCA, PRKCB1, PTEN, RPS6KB1 22 AKT1(4), EIF4A1(5), EIF4A2(9), EIF4E(2), EIF4G1(15), EIF4G2(7), EIF4G3(24), GHR(8), IRS1(13), MAPK1(2), MAPK14(4), MAPK3(3), MKNK1(3), PABPC1(10), PDK2(5), PDPK1(3), PIK3CA(172), PIK3R1(100), PRKCA(10), PTEN(228), RPS6KB1(5) 10144798 632 216 417 49 92 134 132 39 191 44 <1.00e-15 <1.00e-15 <4.76e-14
2 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(4), AKT2(6), AKT3(11), BPNT1(3), GRB2(3), ILK(5), MAPK1(2), MAPK3(3), PDK1(2), PIK3CA(172), PIK3CD(12), PTEN(228), PTK2B(16), RBL2(19), SHC1(7), SOS1(13) 7243620 506 208 307 39 92 126 107 36 117 28 <1.00e-15 <1.00e-15 <4.76e-14
3 SIG_IL4RECEPTOR_IN_B_LYPHOCYTES Genes related to IL4 rceptor signaling in B lymphocytes AKT1, AKT2, AKT3, BAD, BCL2, GRB2, GSK3A, GSK3B, IL4R, IRS1, IRS2, JAK1, JAK3, MAP4K1, MAPK1, MAPK3, PDK1, PIK3CA, PIK3CD, PIK3R1, PPP1R13B, RAF1, SHC1, SOCS1, SOS1, SOS2, STAT6 25 AKT1(4), AKT2(6), AKT3(11), BAD(2), GRB2(3), GSK3A(10), GSK3B(13), IL4R(6), IRS1(13), JAK1(20), JAK3(10), MAP4K1(11), MAPK1(2), MAPK3(3), PDK1(2), PIK3CA(172), PIK3CD(12), PIK3R1(100), PPP1R13B(9), RAF1(8), SHC1(7), SOS1(13), SOS2(17), STAT6(10) 12574116 464 202 337 55 106 123 119 5 95 16 9.87e-11 <1.00e-15 <4.76e-14
4 HCMVPATHWAY Cytomegalovirus activates MAP kinase pathways in the host cell, inducing transcription of viral genes. AKT1, CREB1, MAP2K1, MAP2K2, MAP2K3, MAP2K6, MAP3K1, MAPK1, MAPK14, MAPK3, NFKB1, PIK3CA, PIK3R1, RB1, RELA, SP1 16 AKT1(4), CREB1(6), MAP2K1(2), MAP2K2(5), MAP2K3(7), MAP2K6(10), MAP3K1(30), MAPK1(2), MAPK14(4), MAPK3(3), NFKB1(10), PIK3CA(172), PIK3R1(100), RB1(26), RELA(6), SP1(7) 7166136 394 200 272 31 63 112 107 4 89 19 2.19e-12 <1.00e-15 <4.76e-14
5 IL7PATHWAY IL-7 is required for B and T cell development and proliferation and may contribute to activation of VDJ recombination. BCL2, CREBBP, EP300, FYN, IL2RG, IL7, IL7R, JAK1, JAK3, LCK, NMI, PIK3CA, PIK3R1, PTK2B, STAT5A, STAT5B 16 CREBBP(32), EP300(32), FYN(7), IL2RG(13), IL7(1), IL7R(12), JAK1(20), JAK3(10), LCK(5), NMI(3), PIK3CA(172), PIK3R1(100), PTK2B(16), STAT5A(5), STAT5B(7) 10213532 435 200 312 56 77 121 115 6 100 16 3.60e-08 <1.00e-15 <4.76e-14
6 PAR1PATHWAY Activated extracellular thrombin cleaves and activates the G-protein coupled receptors PAR1 and PAR4, which activate platelets. ADCY1, ARHA, ARHGEF1, F2, F2R, F2RL3, GNA12, GNA13, GNAI1, GNAQ, GNB1, GNGT1, MAP3K7, PIK3CA, PIK3R1, PLCB1, PPP1R12B, PRKCA, PRKCB1, PTK2B, ROCK1 19 ADCY1(21), ARHGEF1(12), F2(8), F2R(6), GNA12(8), GNA13(7), GNAI1(5), GNAQ(3), GNB1(2), GNGT1(1), MAP3K7(9), PIK3CA(172), PIK3R1(100), PLCB1(5), PPP1R12B(20), PRKCA(10), PTK2B(16), ROCK1(22) 9289594 427 199 304 63 96 111 112 7 84 17 2.95e-06 <1.00e-15 <4.76e-14
7 ACHPATHWAY Nicotinic acetylcholine receptors are ligand-gated ion channels that primarily mediate neuromuscular signaling and may inhibit neuronal apoptosis via the AKT pathway. AKT1, BAD, CHRNB1, CHRNG, FOXO3A, MUSK, PIK3CA, PIK3R1, PTK2, PTK2B, RAPSN, SRC, TERT, TNFSF6, YWHAH 13 AKT1(4), BAD(2), CHRNB1(2), CHRNG(4), MUSK(15), PIK3CA(172), PIK3R1(100), PTK2(12), PTK2B(16), RAPSN(2), SRC(3), TERT(4), YWHAH(3) 5901003 339 197 220 43 57 93 94 4 76 15 2.46e-06 <1.00e-15 <4.76e-14
8 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 AKT1(4), BAD(2), BCL2L1(4), CASP9(3), CDC42(4), CHUK(8), ELK1(3), H2AFX(1), HRAS(1), MAP2K1(2), MAPK3(3), NFKB1(10), PIK3CA(172), PIK3R1(100), RAC1(1), RAF1(8), RALA(6), RALBP1(6), RALGDS(9), RELA(6), RHOA(3) 6942603 356 197 235 28 56 106 95 4 78 17 4.18e-12 <1.00e-15 <4.76e-14
9 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 B2M(3), HLA-A(1), IL18(2), ITGB1(8), KLRC1(7), KLRC2(3), KLRC3(1), KLRC4(5), KLRD1(3), MAP2K1(2), MAPK3(3), PAK1(3), PIK3CA(172), PIK3R1(100), PTK2B(16), PTPN6(6), RAC1(1), SYK(4), VAV1(12) 6852023 352 196 232 34 59 99 93 5 81 15 2.61e-09 <1.00e-15 <4.76e-14
10 CTLA4PATHWAY T cell activation requires interaction with an antigen-MHC-I complex on an antigen-presenting cell (APC), as well as CD28 interaction with the APC's CD80 or 86. CD28, CD3D, CD3E, CD3G, CD3Z, CD80, CD86, CTLA4, GRB2, HLA-DRA, HLA-DRB1, ICOS, ICOSL, IL2, ITK, LCK, PIK3CA, PIK3R1, PTPN11, TRA@, TRB@ 17 CD28(3), CD3D(6), CD3E(2), CD3G(3), CD80(5), CD86(5), CTLA4(2), GRB2(3), HLA-DRA(1), ICOS(3), IL2(2), ITK(7), LCK(5), PIK3CA(172), PIK3R1(100), PTPN11(8) 4602586 327 194 208 19 48 91 88 5 80 15 1.67e-12 <1.00e-15 <4.76e-14

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 HSA00627_1,4_DICHLOROBENZENE_DEGRADATION Genes involved in 1,4-dichlorobenzene degradation CMBL 1 CMBL(3) 187727 3 3 3 1 0 1 0 1 1 0 0.81 0.21 1
2 TCAPOPTOSISPATHWAY HIV infection upregulates Fas ligand in macrophages and CD4 in helper T cells, leading to widespread Fas-induced T cell apoptosis. CCR5, CD28, CD3D, CD3E, CD3G, CD3Z, CD4, TNFRSF6, TNFSF6, TRA@, TRB@ 6 CCR5(6), CD28(3), CD3D(6), CD3E(2), CD3G(3), CD4(6) 1210424 26 16 26 5 3 16 0 0 7 0 0.16 0.24 1
3 PEPIPATHWAY Proepithelin (PEPI) induces epithelial cells to secrete IL-8, which promotes elastase secretion by neutrophils. ELA1, ELA2, ELA2A, ELA2B, ELA3B, GRN, IL8, SLPI 3 GRN(5), IL8(3), SLPI(2) 572860 10 10 9 0 2 5 2 0 1 0 0.057 0.27 1
4 HSA00472_D_ARGININE_AND_D_ORNITHINE_METABOLISM Genes involved in D-arginine and D-ornithine metabolism DAO 1 DAO(8) 264662 8 6 8 1 2 4 2 0 0 0 0.3 0.35 1
5 TCRMOLECULE T Cell Receptor and CD3 Complex CD3D, CD3E, CD3G, CD3Z, TRA@, TRB@ 3 CD3D(6), CD3E(2), CD3G(3) 433293 11 7 11 1 1 7 0 0 3 0 0.18 0.43 1
6 LDLPATHWAY Low density lipoproteins (LDL) are present in blood plasma, contain cholesterol and triglycerides, and contribute to atherogenic plaque formation. ACAT1, CCL2, CSF1, IL6, LDLR, LPL 6 ACAT1(6), CSF1(6), IL6(5), LDLR(6), LPL(16) 1914084 39 23 39 7 10 15 9 0 5 0 0.057 0.44 1
7 IL17PATHWAY Activated T cells secrete IL-17, which stimulates fibroblasts and other cells to secrete inflammatory and hematopoietic cytokines. CD2, CD34, CD3D, CD3E, CD3G, CD3Z, CD4, CD58, CD8A, CSF3, IL17, IL3, IL6, IL8, KITLG, TRA@, TRB@ 13 CD2(4), CD34(1), CD3D(6), CD3E(2), CD3G(3), CD4(6), CD58(2), CD8A(2), CSF3(1), IL3(2), IL6(5), IL8(3), KITLG(3) 2309359 40 27 40 9 6 20 4 0 10 0 0.18 0.47 1
8 HSA00643_STYRENE_DEGRADATION Genes involved in styrene degradation FAH, GSTZ1, HGD 3 FAH(6), GSTZ1(5), HGD(4) 822142 15 12 15 2 5 4 4 0 2 0 0.11 0.5 1
9 HSA00031_INOSITOL_METABOLISM Genes involved in inositol metabolism ALDH6A1, TPI1 2 ALDH6A1(6), TPI1(2) 582980 8 7 8 1 0 3 1 0 4 0 0.27 0.56 1
10 HSA00401_NOVOBIOCIN_BIOSYNTHESIS Genes involved in novobiocin biosynthesis GOT1, GOT2, TAT 3 GOT1(9), GOT2(3), TAT(7) 959929 19 13 19 2 7 6 5 1 0 0 0.088 0.63 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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