Mutation Analysis (MutSig v2.0)
Breast Invasive Carcinoma (Primary solid tumor)
23 May 2013  |  analyses__2013_05_23
Maintainer Information
Citation Information
doi:10.7908/C1J38QJZ
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/C1J38QJZ
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: BRCA-TP

  • Number of patients in set: 772

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:BRCA-TP.final_analysis_set.maf

  • Significantly mutated genes (q ≤ 0.1): 76

  • Mutations seen in COSMIC: 727

  • Significantly mutated genes in COSMIC territory: 16

  • Genes with clustered mutations (≤ 3 aa apart): 270

  • Significantly mutated genesets: 123

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

Mutation Preprocessing

  • Read 772 MAFs of type "WashU"

  • Total number of mutations in input MAFs: 47116

  • After removing 330 mutations outside chr1-24: 46786

  • After removing 559 blacklisted mutations: 46227

  • After removing 1703 noncoding mutations: 44524

  • After collapsing adjacent/redundant mutations: 44522

Mutation Filtering

  • Number of mutations before filtering: 44522

  • After removing 4090 mutations outside gene set: 40432

  • After removing 85 mutations outside category set: 40347

  • After removing 11 "impossible" mutations in

  • gene-patient-category bins of zero coverage: 36161

Results
Breakdown of Mutations by Type

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

type count
Frame_Shift_Del 1246
Frame_Shift_Ins 704
In_Frame_Del 687
In_Frame_Ins 233
Missense_Mutation 25869
Nonsense_Mutation 1984
Nonstop_Mutation 38
Silent 8733
Splice_Site 853
Total 40347
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 5166 1101604176 4.7e-06 4.7 3.2 2.2
*Cp(A/C/T)->T 5793 9664813395 6e-07 0.6 0.41 1.7
C->(G/A) 9406 10766417571 8.7e-07 0.87 0.59 4.9
A->mut 5498 10671091617 5.2e-07 0.52 0.35 3.8
indel+null 5666 21437509188 2.6e-07 0.26 0.18 NaN
double_null 79 21437509188 3.7e-09 0.0037 0.0025 NaN
Total 31608 21437509188 1.5e-06 1.5 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: BRCA-TP.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->T

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

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

  • 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: 76. 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 DSPP dentin sialophosphoprotein 2697497 30 26 17 0 0 11 4 8 7 0 5.00e-15 0.00226 0.95 0.0002 0.000 0.000
2 PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (alpha) 1797680 21 21 20 1 0 3 2 3 13 0 5.88e-15 0.352 0.081 6.2e-06 0.000 0.000
3 NCOR2 nuclear receptor co-repressor 2 3826500 29 29 7 1 1 0 2 0 26 0 2.89e-12 0.731 1 5.2e-06 5.55e-16 1.06e-12
4 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 2526504 287 261 49 4 5 101 11 154 16 0 2.66e-15 <1.00e-15 0 0 <1.00e-15 <1.06e-12
5 TP53 tumor protein p53 974889 261 257 145 3 35 28 32 62 104 0 2.11e-15 <1.00e-15 0 0 <1.00e-15 <1.06e-12
6 GATA3 GATA binding protein 3 764273 84 81 50 1 0 1 1 4 77 1 <1.00e-15 0.473 0.61 0 <1.00e-15 <1.06e-12
7 NCOA3 nuclear receptor coactivator 3 3363126 30 29 12 0 1 2 3 2 22 0 6.33e-15 0.156 1 0 <1.00e-15 <1.06e-12
8 AKT1 v-akt murine thymoma viral oncogene homolog 1 951700 19 19 2 1 0 18 0 1 0 0 7.99e-15 7.29e-05 0.000052 0 <1.00e-15 <1.06e-12
9 AOAH acyloxyacyl hydrolase (neutrophil) 1514305 19 19 1 3 0 0 0 0 19 0 4.45e-14 1.000 1 0 <1.00e-15 <1.06e-12
10 MAP3K4 mitogen-activated protein kinase kinase kinase 4 3667040 18 18 5 2 0 1 0 0 17 0 1.03e-05 0.877 0.74 0 <1.00e-15 <1.06e-12
11 NR1H2 nuclear receptor subfamily 1, group H, member 2 802056 18 18 5 0 2 0 0 1 15 0 5.55e-15 0.390 1 0 <1.00e-15 <1.06e-12
12 MEF2A myocyte enhancer factor 2A 1255054 14 14 3 0 0 0 0 1 13 0 2.04e-09 0.745 0 0 <1.00e-15 <1.06e-12
13 ZNF384 zinc finger protein 384 1360722 14 14 1 1 0 0 0 0 14 0 9.65e-09 1.000 1 0 <1.00e-15 <1.06e-12
14 RBMX RNA binding motif protein, X-linked 966111 13 13 2 1 0 0 0 0 13 0 5.28e-10 1.000 0.37 0 <1.00e-15 <1.06e-12
15 TPRX1 tetra-peptide repeat homeobox 1 736132 8 7 4 0 0 0 0 4 4 0 0.000108 0.180 0.91 0 <1.00e-15 <1.06e-12
16 DCP1B DCP1 decapping enzyme homolog B (S. cerevisiae) 1373345 5 5 1 1 0 0 0 0 5 0 0.0237 1.000 0.98 0 <1.00e-15 <1.06e-12
17 RUNX1 runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene) 794236 25 25 23 3 0 2 1 4 17 1 4.33e-15 0.530 0.36 0.011 1.89e-15 1.88e-12
18 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 956652 29 29 26 0 1 0 3 4 20 1 5.55e-15 0.0931 0.27 0.087 1.75e-14 1.65e-11
19 TBX3 T-box 3 (ulnar mammary syndrome) 991293 18 18 17 0 0 3 1 1 13 0 1.21e-14 0.0585 0.86 0.045 1.98e-14 1.76e-11
20 CBFB core-binding factor, beta subunit 359167 16 16 16 1 0 4 3 4 5 0 6.99e-15 0.142 0.34 0.13 3.16e-14 2.68e-11
21 MAP2K4 mitogen-activated protein kinase kinase 4 863577 32 32 28 0 3 2 5 2 20 0 6.22e-15 0.0109 0.25 0.16 3.63e-14 2.92e-11
22 CDH1 cadherin 1, type 1, E-cadherin (epithelial) 1998729 56 55 49 2 2 4 2 1 47 0 1.55e-15 0.00243 0.51 1 5.45e-14 4.19e-11
23 MAP3K1 mitogen-activated protein kinase kinase kinase 1 3179186 69 57 65 3 0 1 6 9 37 16 3.77e-15 0.0748 0.32 0.64 8.34e-14 6.13e-11
24 FOXA1 forkhead box A1 763360 15 15 15 0 1 3 2 4 5 0 2.14e-13 0.0368 0.13 0.012 9.04e-14 6.37e-11
25 MLL3 myeloid/lymphoid or mixed-lineage leukemia 3 11396219 58 56 56 1 2 10 6 4 34 2 1.24e-14 0.00186 0.41 0.38 1.61e-13 1.09e-10
26 ATN1 atrophin 1 2206723 18 17 9 1 0 5 2 0 11 0 2.55e-08 0.248 0.98 0.00058 3.84e-10 2.50e-07
27 SF3B1 splicing factor 3b, subunit 1, 155kDa 3111950 14 14 7 0 0 1 0 12 1 0 1.12e-05 0.0132 0.065 5.2e-06 1.43e-09 8.95e-07
28 CCDC144NL coiled-coil domain containing 144 family, N-terminal like 495337 8 8 3 0 1 0 0 0 7 0 4.15e-07 0.576 1 0.00015 1.51e-09 9.13e-07
29 MUC12 mucin 12, cell surface associated 6560731 50 44 38 8 12 7 13 9 8 1 3.93e-10 0.0268 0.97 0.33 3.11e-09 1.82e-06
30 KRTAP4-7 keratin associated protein 4-7 345100 7 7 2 1 0 0 1 6 0 0 1.56e-07 0.638 0.96 0.0036 1.27e-08 7.17e-06
31 ZFP36L1 zinc finger protein 36, C3H type-like 1 695039 10 10 10 0 0 1 1 1 7 0 4.99e-08 0.306 0.83 0.043 4.52e-08 2.47e-05
32 NCOR1 nuclear receptor co-repressor 1 5748805 31 31 31 2 0 2 5 2 21 1 4.67e-09 0.0529 0.65 0.64 6.18e-08 3.26e-05
33 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 544372 6 6 3 0 0 1 4 0 1 0 3.51e-06 0.517 0.15 0.0016 1.16e-07 5.93e-05
34 PHLDA1 pleckstrin homology-like domain, family A, member 1 522212 9 9 5 0 0 0 4 0 5 0 2.99e-07 0.410 0.88 0.022 1.34e-07 6.65e-05
35 VEZF1 vascular endothelial zinc finger 1 1198490 8 8 3 0 0 0 1 0 7 0 0.000127 0.835 1 0.000056 1.41e-07 6.81e-05
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: 16. Number of genes displayed: 10

rank gene description n cos n_cos N_cos cos_ev p q
1 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 287 220 268 169840 161927 0 0
2 TP53 tumor protein p53 261 356 248 274832 47662 0 0
3 CDH1 cadherin 1, type 1, E-cadherin (epithelial) 56 185 23 142820 37 0 0
4 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 29 767 29 592124 1024 0 0
5 MAP2K4 mitogen-activated protein kinase kinase 4 32 15 6 11580 10 3.4e-13 3e-10
6 PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (alpha) 21 33 12 25476 20 6.6e-13 4.2e-10
7 GATA3 GATA binding protein 3 84 34 32 26248 212 6.8e-13 4.2e-10
8 ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian) 12 42 8 32424 50 8.3e-13 4.5e-10
9 RUNX1 runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene) 25 178 17 137416 57 3e-12 1.5e-09
10 FGFR2 fibroblast growth factor receptor 2 (bacteria-expressed kinase, keratinocyte growth factor receptor, craniofacial dysostosis 1, Crouzon syndrome, Pfeiffer syndrome, Jackson-Weiss syndrome) 7 51 5 39372 21 5.2e-09 2.3e-06

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
7343 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 287 0 8908 11422 12316 8908 11422 12316
10236 TP53 tumor protein p53 261 0 439 1192 2731 439 1192 2731
353 AKT1 v-akt murine thymoma viral oncogene homolog 1 19 0 153 153 153 153 153 153
8775 SF3B1 splicing factor 3b, subunit 1, 155kDa 14 0 28 28 29 28 28 29
6263 MUC12 mucin 12, cell surface associated 50 0 26 32 39 26 32 39
2803 DSPP dentin sialophosphoprotein 30 0 18 39 52 18 39 52
5343 KRTAP4-7 keratin associated protein 4-7 7 0 15 15 15 15 15 15
1688 CDH1 cadherin 1, type 1, E-cadherin (epithelial) 56 0 11 13 18 11 13 18
2672 DNAH14 dynein, axonemal, heavy chain 14 11 0 10 10 10 10 10 10
5269 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 6 0 10 10 10 10 10 10

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: 123. 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 HSA04620_TOLL_LIKE_RECEPTOR_SIGNALING_PATHWAY Genes involved in Toll-like receptor signaling pathway AKT1, AKT2, AKT3, CASP8, CCL3, CCL4, CCL5, CD14, CD40, CD80, CD86, CHUK, CXCL10, CXCL11, CXCL9, FADD, FOS, IFNA1, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA2, IFNA21, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNAR1, IFNAR2, IFNB1, IKBKB, IKBKE, IKBKG, IL12A, IL12B, IL1B, IL6, IL8, IRAK1, IRAK4, IRF3, IRF5, IRF7, JUN, LBP, LY96, MAP2K1, MAP2K2, MAP2K3, MAP2K4, MAP2K6, MAP2K7, MAP3K7, MAP3K7IP1, MAP3K7IP2, MAP3K8, MAPK1, MAPK10, MAPK11, MAPK12, MAPK13, MAPK14, MAPK3, MAPK8, MAPK9, MYD88, NFKB1, NFKB2, NFKBIA, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, RAC1, RELA, RIPK1, SPP1, STAT1, TBK1, TICAM1, TICAM2, TIRAP, TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TNF, TOLLIP, TRAF3, TRAF6 98 AKT1(19), AKT2(3), AKT3(4), CASP8(10), CD14(2), CD40(1), CD86(2), CHUK(1), IFNA1(1), IFNA10(1), IFNA13(1), IFNA14(2), IFNA16(1), IFNA17(1), IFNA2(3), IFNA21(1), IFNA4(1), IFNA6(2), IFNAR1(1), IFNAR2(1), IFNB1(1), IKBKB(4), IKBKE(2), IL12A(1), IL12B(1), IL6(2), IRAK1(2), IRAK4(3), IRF3(3), IRF5(1), IRF7(1), JUN(3), LBP(1), MAP2K1(1), MAP2K2(1), MAP2K3(2), MAP2K4(32), MAP2K6(1), MAP2K7(1), MAP3K7(1), MAP3K8(2), MAPK1(1), MAPK10(2), MAPK13(1), MAPK14(2), MAPK3(1), MAPK8(2), NFKB1(4), NFKB2(3), NFKBIA(1), PIK3CA(287), PIK3CB(6), PIK3CD(4), PIK3CG(3), PIK3R1(21), PIK3R3(2), RELA(1), RIPK1(3), SPP1(2), STAT1(1), TBK1(1), TICAM1(5), TIRAP(1), TLR1(1), TLR2(1), TLR3(5), TLR4(13), TLR5(2), TLR7(8), TLR8(3), TLR9(1), TRAF3(2), TRAF6(3) 97377478 517 400 253 42 27 160 56 187 85 2 <1.00e-15 <1.00e-15 <1.76e-14
2 HSA04012_ERBB_SIGNALING_PATHWAY Genes involved in ErbB signaling pathway ABL1, ABL2, AKT1, AKT2, AKT3, ARAF, AREG, BAD, BRAF, BTC, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CBL, CBLB, CBLC, CDKN1A, CDKN1B, CRK, CRKL, EGF, EGFR, EIF4EBP1, ELK1, ERBB2, ERBB3, ERBB4, EREG, FRAP1, GAB1, GRB2, GSK3B, HBEGF, HRAS, JUN, KRAS, MAP2K1, MAP2K2, MAP2K4, MAP2K7, MAPK1, MAPK10, MAPK3, MAPK8, MAPK9, MYC, NCK1, NCK2, NRAS, NRG1, NRG2, NRG3, NRG4, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PLCG1, PLCG2, PRKCA, PRKCB1, PRKCG, PTK2, RAF1, RPS6KB1, RPS6KB2, SHC1, SHC2, SHC3, SHC4, SOS1, SOS2, SRC, STAT5A, STAT5B, TGFA 85 ABL1(5), ABL2(4), AKT1(19), AKT2(3), AKT3(4), ARAF(4), AREG(1), BRAF(3), BTC(1), CAMK2A(2), CAMK2D(4), CAMK2G(1), CBL(4), CBLB(10), CBLC(2), CDKN1B(7), CRK(1), CRKL(1), EGF(3), EGFR(5), ELK1(2), ERBB2(12), ERBB3(11), ERBB4(6), GAB1(2), GRB2(1), JUN(3), KRAS(6), MAP2K1(1), MAP2K2(1), MAP2K4(32), MAP2K7(1), MAPK1(1), MAPK10(2), MAPK3(1), MAPK8(2), MYC(1), NCK1(1), NCK2(1), NRAS(1), NRG1(2), NRG3(4), PAK1(2), PAK2(2), PAK3(2), PAK4(1), PAK6(1), PAK7(2), PIK3CA(287), PIK3CB(6), PIK3CD(4), PIK3CG(3), PIK3R1(21), PIK3R3(2), PLCG1(6), PLCG2(3), PRKCG(2), PTK2(5), RAF1(1), RPS6KB1(2), RPS6KB2(4), SHC1(1), SHC2(1), SHC3(1), SHC4(2), SOS1(4), SOS2(4), STAT5A(4), STAT5B(5), TGFA(1) 112604599 557 393 289 53 39 160 78 197 83 0 <1.00e-15 <1.00e-15 <1.76e-14
3 PPARAPATHWAY Peroxisome proliferators regulate gene expression via PPAR/RXR heterodimers which bind to peroxisome-proliferator response elements (PPREs). ACOX1, APOA1, APOA2, CD36, CITED2, CPT1B, CREBBP, DUSP1, DUT, EHHADH, EP300, FABP1, FAT, FRA8B, HSD17B4, HSPA1A, HSPCA, INS, JUN, LPL, MAPK1, MAPK3, ME1, MRPL11, MYC, NCOA1, NCOR1, NCOR2, NFKBIA, NOS2A, NR0B2, NR1H3, NR2F1, NRIP1, PDGFA, PIK3CA, PIK3R1, PPARA, PPARBP, PPARGC1, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, PRKCA, PRKCB1, PTGS2, RB1, RELA, RXRA, SP1, SRA1, STAT5A, STAT5B, TNF 49 ACOX1(2), CD36(1), CITED2(2), CPT1B(2), CREBBP(7), EHHADH(3), EP300(7), FABP1(1), HSD17B4(6), JUN(3), LPL(1), MAPK1(1), MAPK3(1), MRPL11(1), MYC(1), NCOA1(2), NCOR1(31), NCOR2(29), NFKBIA(1), NR0B2(2), NR2F1(1), NRIP1(3), PIK3CA(287), PIK3R1(21), PPARA(2), PRKACG(1), PRKAR1A(4), PRKAR2A(1), PRKAR2B(1), PTGS2(2), RB1(16), RELA(1), RXRA(1), SP1(3), SRA1(1), STAT5A(4), STAT5B(5) 68924350 458 361 195 30 20 120 40 172 105 1 <1.00e-15 <1.00e-15 <1.76e-14
4 APOPTOSIS_GENMAPP APAF1, BAK1, BCL2L7P1, BAX, BCL2, BCL2L1, BID, BIRC2, BIRC3, BIRC4, CASP2, CASP3, CASP6, CASP7, CASP8, CASP9, CYCS, FADD, FAS, FASLG, GZMB, IKBKG, JUN, MAP2K4, MAP3K1, MAP3K14, MAPK10, MCL1, MDM2, MYC, NFKB1, NFKBIA, PARP1, PRF1, RELA, RIPK1, TNF, TNFRSF1A, TNFRSF1B, TNFSF10, TP53, TRADD, TRAF1, TRAF2 40 APAF1(3), BAK1(2), BAX(2), BID(4), BIRC3(1), CASP2(3), CASP6(2), CASP7(1), CASP8(10), CASP9(1), FAS(1), FASLG(2), JUN(3), MAP2K4(32), MAP3K1(69), MAPK10(2), MCL1(1), MDM2(2), MYC(1), NFKB1(4), NFKBIA(1), PARP1(3), PRF1(2), RELA(1), RIPK1(3), TNFRSF1A(1), TP53(261), TRAF1(1) 40657541 419 357 294 14 51 46 53 78 175 16 <1.00e-15 <1.00e-15 <1.76e-14
5 GLEEVECPATHWAY The drug Gleevec specifically targets the abnormal bcr-abl protein, an apoptosis inhibitor present in chronic myeloid leukemia. AKT1, BCL2, BCR, CRKL, FOS, GRB2, HRAS, JAK2, JUN, MAP2K1, MAP2K4, MAP3K1, MAPK3, MAPK8, MYC, PIK3CA, PIK3R1, RAF1, SOS1, STAT1, STAT5A, STAT5B 22 AKT1(19), BCR(3), CRKL(1), GRB2(1), JAK2(5), JUN(3), MAP2K1(1), MAP2K4(32), MAP3K1(69), MAPK3(1), MAPK8(2), MYC(1), PIK3CA(287), PIK3R1(21), RAF1(1), SOS1(4), STAT1(1), STAT5A(4), STAT5B(5) 30563652 461 355 197 16 15 129 31 173 97 16 <1.00e-15 <1.00e-15 <1.76e-14
6 TCRPATHWAY T cell receptors bind to foreign peptides presented by MHC molecules and induce T cell activation. CALM1, CALM2, CALM3, CD3D, CD3E, CD3G, CD3Z, ELK1, FOS, FYN, GRB2, HRAS, JUN, LAT, LCK, MAP2K1, MAP2K4, MAP3K1, MAPK3, MAPK8, NFATC1, NFATC2, NFATC3, NFATC4, NFKB1, NFKBIA, PIK3CA, PIK3R1, PLCG1, PPP3CA, PPP3CB, PPP3CC, PRKCA, PRKCB1, PTPN7, RAC1, RAF1, RASA1, RELA, SHC1, SOS1, SYT1, TRA@, TRB@, VAV1, ZAP70 42 CD3E(2), CD3G(2), ELK1(2), GRB2(1), JUN(3), LAT(1), LCK(1), MAP2K1(1), MAP2K4(32), MAP3K1(69), MAPK3(1), MAPK8(2), NFATC2(2), NFATC3(4), NFATC4(5), NFKB1(4), NFKBIA(1), PIK3CA(287), PIK3R1(21), PLCG1(6), PPP3CA(4), PPP3CB(3), PTPN7(2), RAF1(1), RASA1(2), RELA(1), SHC1(1), SOS1(4), VAV1(4), ZAP70(2) 52467488 471 355 224 29 20 123 40 176 96 16 <1.00e-15 <1.00e-15 <1.76e-14
7 HSA04370_VEGF_SIGNALING_PATHWAY Genes involved in VEGF signaling pathway AKT1, AKT2, AKT3, BAD, CASP9, CDC42, CHP, HRAS, KDR, KRAS, MAP2K1, MAP2K2, MAPK1, MAPK11, MAPK12, MAPK13, MAPK14, MAPK3, MAPKAPK2, MAPKAPK3, NFAT5, NFATC1, NFATC2, NFATC3, NFATC4, NOS3, NRAS, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PLA2G10, PLA2G12A, PLA2G12B, PLA2G1B, PLA2G2A, PLA2G2D, PLA2G2E, PLA2G2F, PLA2G3, PLA2G4A, PLA2G5, PLA2G6, PLCG1, PLCG2, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRKCA, PRKCB1, PRKCG, PTGS2, PTK2, PXN, RAC1, RAC2, RAC3, RAF1, SH2D2A, SHC2, SPHK1, SPHK2, SRC, VEGFA 69 AKT1(19), AKT2(3), AKT3(4), CASP9(1), KDR(2), KRAS(6), MAP2K1(1), MAP2K2(1), MAPK1(1), MAPK13(1), MAPK14(2), MAPK3(1), MAPKAPK2(1), MAPKAPK3(1), NFAT5(6), NFATC2(2), NFATC3(4), NFATC4(5), NOS3(3), NRAS(1), PIK3CA(287), PIK3CB(6), PIK3CD(4), PIK3CG(3), PIK3R1(21), PIK3R3(2), PLA2G12A(1), PLA2G2D(1), PLA2G2E(1), PLA2G2F(1), PLA2G3(2), PLA2G4A(7), PLA2G6(2), PLCG1(6), PLCG2(3), PPP3CA(4), PPP3CB(3), PPP3R1(1), PRKCG(2), PTGS2(2), PTK2(5), RAF1(1), SH2D2A(1), SHC2(1), SPHK2(2) 77057103 434 354 175 44 18 150 48 173 45 0 <1.00e-15 <1.00e-15 <1.76e-14
8 SIG_BCR_SIGNALING_PATHWAY Members of the BCR signaling pathway AKT1, AKT2, AKT3, BAD, BCL2, BCR, BLNK, BTK, CD19, CD22, CD81, CR2, CSK, DAG1, FLOT1, FLOT2, GRB2, GSK3A, GSK3B, INPP5D, ITPR1, ITPR2, ITPR3, LYN, MAP4K1, MAPK1, MAPK3, NFATC1, NFATC2, NR0B2, PDK1, PIK3CA, PIK3CD, PIK3R1, PLCG2, PPP1R13B, PPP3CA, PPP3CB, PPP3CC, PTPRC, RAF1, SHC1, SOS1, SOS2, SYK, VAV1 46 AKT1(19), AKT2(3), AKT3(4), BCR(3), BLNK(1), BTK(4), CD19(3), CD22(1), CR2(4), DAG1(1), FLOT1(1), FLOT2(2), GRB2(1), GSK3A(3), INPP5D(4), ITPR1(10), ITPR2(7), ITPR3(6), LYN(4), MAP4K1(4), MAPK1(1), MAPK3(1), NFATC2(2), NR0B2(2), PDK1(1), PIK3CA(287), PIK3CD(4), PIK3R1(21), PLCG2(3), PPP1R13B(3), PPP3CA(4), PPP3CB(3), PTPRC(3), RAF1(1), SHC1(1), SOS1(4), SOS2(4), SYK(2), VAV1(4) 80779691 436 353 180 38 23 147 45 179 42 0 <1.00e-15 <1.00e-15 <1.76e-14
9 HSA04150_MTOR_SIGNALING_PATHWAY Genes involved in mTOR signaling pathway AKT1, AKT2, AKT3, BRAF, CAB39, DDIT4, EIF4B, EIF4EBP1, FIGF, FRAP1, GBL, HIF1A, IGF1, INS, KIAA1303, LYK5, MAPK1, MAPK3, PDPK1, PGF, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PRKAA1, PRKAA2, RHEB, RICTOR, RPS6, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KA6, RPS6KB1, RPS6KB2, STK11, TSC1, TSC2, ULK1, ULK2, ULK3, VEGFA, VEGFB, VEGFC 44 AKT1(19), AKT2(3), AKT3(4), BRAF(3), EIF4B(1), FIGF(2), HIF1A(1), IGF1(1), MAPK1(1), MAPK3(1), PIK3CA(287), PIK3CB(6), PIK3CD(4), PIK3CG(3), PIK3R1(21), PIK3R3(2), PRKAA1(1), PRKAA2(3), RHEB(1), RICTOR(3), RPS6(2), RPS6KA1(2), RPS6KA2(4), RPS6KA3(4), RPS6KA6(3), RPS6KB1(2), RPS6KB2(4), STK11(2), TSC1(4), TSC2(2), ULK1(1), ULK2(4), ULK3(2) 57150754 403 341 147 27 17 142 31 172 41 0 <1.00e-15 <1.00e-15 <1.76e-14
10 RAC1PATHWAY Rac-1 is a Rho family G protein that stimulates formation of actin-dependent structures such as filopodia and lamellopodia. ARFIP2, CDK5, CDK5R1, CFL1, CHN1, LIMK1, MAP3K1, MYL2, MYLK, NCF2, PAK1, PDGFRA, PIK3CA, PIK3R1, PLD1, PPP1R12B, RAC1, RALBP1, RPS6KB1, TRIO, VAV1, WASF1 22 CDK5(1), CHN1(3), LIMK1(4), MAP3K1(69), MYLK(8), NCF2(4), PAK1(2), PDGFRA(3), PIK3CA(287), PIK3R1(21), PLD1(5), PPP1R12B(1), RALBP1(1), RPS6KB1(2), TRIO(5), VAV1(4), WASF1(5) 39907968 425 336 182 27 10 119 35 175 70 16 <1.00e-15 <1.00e-15 <1.76e-14

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 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(3), CD34(2), CD3E(2), CD3G(2), CD4(4), CD58(1), CD8A(2), IL6(2), KITLG(3) 7120299 21 21 21 3 0 7 5 4 5 0 0.12 0.022 1
2 FBW7PATHWAY Cyclin E interacts with cell cycle checkpoint kinase cdk2 to allow transcription of genes required for S phase, including transcription of additional cyclin E. CCNE1, CDC34, CDK2, CUL1, E2F1, FBXW7, RB1, SKP1A, TFDP1 7 CCNE1(1), CDK2(1), CUL1(2), E2F1(4), FBXW7(6), TFDP1(2) 7497996 16 16 15 1 5 3 2 3 3 0 0.051 0.042 1
3 METHIONINEPATHWAY Catabolic Pathways for Methionine, Isoleucine, Threonine and Valine BCKDHB, BCKDK, CBS, CTH, MUT 5 BCKDK(5), CBS(2), CTH(3), MUT(3) 5387362 13 13 13 0 2 3 2 2 4 0 0.028 0.049 1
4 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(2), CD28(1), CD3E(2), CD3G(2), CD4(4) 3744423 11 11 11 2 1 4 2 1 3 0 0.31 0.094 1
5 TCRMOLECULE T Cell Receptor and CD3 Complex CD3D, CD3E, CD3G, CD3Z, TRA@, TRB@ 3 CD3E(2), CD3G(2) 1346070 4 4 4 0 0 3 0 1 0 0 0.21 0.12 1
6 IL18PATHWAY Pro-inflammatory IL-18 is activated in macrophages by caspase-1 cleavage and, in conjunction with IL-12, stimulates Th1 cell differentiation. CASP1, IFNG, IL12A, IL12B, IL18, IL2 6 CASP1(1), IFNG(2), IL12A(1), IL12B(1), IL18(1), IL2(1) 3530673 7 7 7 1 1 0 1 4 1 0 0.55 0.13 1
7 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(2), RAB11A(2), RAB1A(2), RAB27A(1), RAB3A(2), RAB6A(1) 4901601 10 10 10 1 0 4 3 0 3 0 0.19 0.13 1
8 SA_PROGRAMMED_CELL_DEATH Programmed cell death, or apoptosis, eliminates damaged or unneeded cells. APAF1, BAD, BAK1, BAX, BCL10, BCL2, BCL2L1, BCL2L11, BID, CASP8AP2, CASP9, CES1 11 APAF1(3), BAK1(2), BAX(2), BCL10(1), BCL2L11(4), BID(4), CASP9(1), CES1(2) 8480554 19 19 18 2 4 5 4 2 4 0 0.13 0.17 1
9 CREMPATHWAY The transcription factor CREM activates a post-meiotic transcriptional cascade culminating in spermatogenesis. ADCY1, CREM, FHL5, FSHB, FSHR, GNAS, XPO1 7 ADCY1(3), CREM(2), FHL5(2), FSHR(4), GNAS(5), XPO1(4) 10143105 20 20 19 2 4 4 4 5 3 0 0.1 0.18 1
10 ATMPATHWAY The tumor-suppressing protein kinase ATM responds to radiation-induced DNA damage by blocking cell-cycle progression and activating DNA repair. ABL1, ATM, BRCA1, CDKN1A, CHEK1, CHEK2, GADD45A, JUN, MAPK8, MDM2, MRE11A, NBS1, NFKB1, NFKBIA, RAD50, RAD51, RBBP8, RELA, TP53, TP73 18 ABL1(5), ATM(18), BRCA1(12), CHEK2(3), JUN(3), MAPK8(2), MDM2(2), MRE11A(2), NFKB1(4), NFKBIA(1), RAD50(2), RAD51(2), RBBP8(4), RELA(1), TP73(1) 31833859 62 57 62 5 7 10 15 9 21 0 0.0046 0.22 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

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)
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