Breast Invasive Carcinoma: Mutation Analysis (MutSig v2.0)
Maintained by Dan DiCara (Broad Institute)
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

- Number of patients in set: 507

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.final_analysis_set.maf

- Significantly mutated genes (q ≤ 0.1): 41

- Mutations seen in COSMIC: 500

- Significantly mutated genes in COSMIC territory: 16

- Genes with clustered mutations (≤ 3 aa apart): 273

- Significantly mutated genesets: 115

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

Mutation Preprocessing

- Read 507 MAFs of type "WashU"

- Total number of mutations in input MAFs: 33982

- After removing 41 mutations outside chr1-24: 33941

- After removing 1665 noncoding mutations: 32276

- After collapsing adjacent/redundant mutations: 31999

Mutation Filtering

- Number of mutations before filtering: 31999

- After removing 1528 mutations outside gene set: 30471

- After removing 148 mutations outside category set: 30323

Results
Breakdown of Mutations by Type

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

type | count
--- | ---
Frame_Shift_Del | 958
Frame_Shift_Ins | 311
In_Frame_Del | 388
In_Frame_Ins | 74
Missense_Mutation | 19287
Nonsense_Mutation | 1398
Nonstop_Mutation | 34
Silent | 7287
Splice_Site | 586
Total | 30323

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 | 3903 | 836685876 | 4.7e-06 | 4.7 | 3.1 | 2.1
*Cp(A/C/T)->T | 4294 | 7060503801 | 6.1e-07 | 0.61 | 0.41 | 1.7
C->(G/A) | 6959 | 7897189677 | 8.8e-07 | 0.88 | 0.59 | 4.8
A->mut | 4125 | 7654859394 | 5.4e-07 | 0.54 | 0.36 | 3.9
indel+null | 3696 | 15552049071 | 2.4e-07 | 0.24 | 0.16 | NaN
double_null | 59 | 15552049071 | 3.8e-09 | 0.0038 | 0.0026 | NaN
Total | 23036 | 15552049071 | 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.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_ks = p-value for clustering of mutations (Kolmogorov-Smirnoff test)

- 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: 41. 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_ks | p_cons | p_joint | p | q
--- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | ---
1 | RUNX1 | runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene) | 630708 | 18 | 18 | 17 | 1 | 0 | 2 | 1 | 3 | 12 | 0 | 7.99e-15 | 0.225 | 0.00023 | 0.26 | 0.00047 | 1.11e-16 | 2.03e-12
2 | MAP2K4 | mitogen-activated protein kinase kinase 4 | 570375 | 20 | 20 | 19 | 0 | 3 | 2 | 2 | 1 | 12 | 0 | 3.66e-15 | 0.0346 | 0.0077 | 0.042 | 0.0071 | 9.99e-16 | 2.29e-12
3 | TP53 | tumor protein p53 | 649467 | 187 | 184 | 113 | 3 | 29 | 23 | 23 | 39 | 73 | 0 | <1.00e-15 | 3.33e-15 | 2e-07 | 2e-07 | 0 | <1.00e-15 | <2.29e-12
4 | PIK3CA | phosphoinositide-3-kinase, catalytic, alpha polypeptide | 1666509 | 194 | 178 | 32 | 3 | 3 | 70 | 8 | 105 | 8 | 0 | <1.00e-15 | <1.00e-15 | 2e-07 | 2e-07 | 0 | <1.00e-15 | <2.29e-12
5 | GATA3 | GATA binding protein 3 | 574431 | 56 | 54 | 34 | 1 | 0 | 1 | 0 | 3 | 51 | 1 | 1.44e-15 | 0.519 | 2e-07 | 0.058 | 0 | <1.00e-15 | <2.29e-12
6 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | 757965 | 12 | 12 | 2 | 1 | 0 | 11 | 0 | 1 | 0 | 0 | 3.23e-10 | 0.00521 | 2e-07 | 0.000036 | 0 | <1.00e-15 | <2.29e-12
7 | OR10J5 | olfactory receptor, family 10, subfamily J, member 5 | 472524 | 2 | 2 | 2 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0.0294 | 0.415 | 0.023 | 0.0015 | 0 | <1.00e-15 | <2.29e-12
8 | ZNF283 | zinc finger protein 283 | 978003 | 2 | 2 | 2 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0.313 | 0.586 | 0.022 | 0.0013 | 0 | <1.00e-15 | <2.29e-12
9 | CDH1 | cadherin 1, type 1, E-cadherin (epithelial) | 1347099 | 33 | 33 | 30 | 1 | 0 | 3 | 1 | 0 | 29 | 0 | 3.00e-15 | 0.0312 | 0.2 | 0.33 | 0.24 | 2.53e-14 | 5.14e-11
10 | MAP3K1 | mitogen-activated protein kinase kinase kinase 1 | 2095431 | 46 | 38 | 45 | 3 | 0 | 0 | 2 | 5 | 24 | 15 | 5.66e-15 | 0.271 | 0.4 | 0.092 | 0.25 | 4.93e-14 | 9.01e-11
11 | PIK3R1 | phosphoinositide-3-kinase, regulatory subunit 1 (alpha) | 1196520 | 14 | 14 | 13 | 1 | 0 | 2 | 2 | 1 | 9 | 0 | 7.16e-11 | 0.610 | 0.000011 | 0.11 | 0.000025 | 6.21e-14 | 9.66e-11
12 | PTEN | phosphatase and tensin homolog (mutated in multiple advanced cancers 1) | 632736 | 17 | 17 | 16 | 0 | 1 | 0 | 2 | 2 | 11 | 1 | 1.40e-14 | 0.181 | 0.082 | 0.3 | 0.13 | 6.34e-14 | 9.66e-11
13 | TBX3 | T-box 3 (ulnar mammary syndrome) | 709800 | 13 | 13 | 13 | 0 | 0 | 2 | 1 | 0 | 10 | 0 | 1.98e-11 | 0.176 | 0.00085 | 0.65 | 0.0019 | 1.21e-12 | 1.71e-09
14 | MLL3 | myeloid/lymphoid or mixed-lineage leukemia 3 | 7571538 | 38 | 37 | 38 | 2 | 0 | 8 | 4 | 3 | 23 | 0 | 8.82e-12 | 0.121 | 0.38 | 0.14 | 0.25 | 6.16e-11 | 8.04e-08
15 | CBFB | core-binding factor, beta subunit | 246909 | 8 | 8 | 8 | 1 | 0 | 4 | 0 | 1 | 3 | 0 | 1.18e-10 | 0.339 | 0.14 | 0.066 | 0.1 | 3.15e-10 | 3.84e-07
16 | CTCF | CCCTC-binding factor (zinc finger protein) | 1127568 | 13 | 13 | 11 | 2 | 1 | 1 | 2 | 2 | 7 | 0 | 1.24e-06 | 0.494 | 0.029 | 0.00038 | 0.00098 | 2.63e-08 | 3.00e-05
17 | SF3B1 | splicing factor 3b, subunit 1, 155kDa | 2047773 | 10 | 10 | 6 | 0 | 0 | 1 | 0 | 8 | 1 | 0 | 0.000133 | 0.0496 | 0.000032 | 0.11 | 1e-05 | 2.85e-08 | 3.07e-05
18 | FOXA1 | forkhead box A1 | 603330 | 8 | 8 | 7 | 0 | 1 | 3 | 2 | 1 | 1 | 0 | 4.12e-06 | 0.0502 | 0.00025 | 0.26 | 0.0004 | 3.46e-08 | 3.51e-05
19 | KLRG2 | killer cell lectin-like receptor subfamily G, member 2 | 228150 | 3 | 3 | 1 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 0.00302 | 0.502 | 2.2e-06 | 0.41 | 1.4e-06 | 8.58e-08 | 8.26e-05
20 | C9orf102 | chromosome 9 open reading frame 102 | 1098162 | 5 | 5 | 3 | 1 | 0 | 3 | 0 | 2 | 0 | 0 | 0.00388 | 0.552 | 3e-06 | 1 | 9.6e-06 | 6.74e-07 | 0.000617
21 | VASN | vasorin | 348309 | 6 | 6 | 3 | 0 | 0 | 0 | 1 | 4 | 1 | 0 | 5.59e-06 | 0.384 | 0.0067 | 0.9 | 0.017 | 1.61e-06 | 0.00140
22 | C1orf65 | chromosome 1 open reading frame 65 | 581529 | 7 | 7 | 5 | 0 | 1 | 4 | 1 | 1 | 0 | 0 | 2.27e-05 | 0.0373 | 0.0048 | 0.67 | 0.014 | 4.88e-06 | 0.00406
23 | TBL1XR1 | transducin (beta)-like 1 X-linked receptor 1 | 811707 | 8 | 8 | 7 | 0 | 0 | 0 | 1 | 1 | 4 | 2 | 7.32e-07 | 0.445 | 0.44 | 0.69 | 0.6 | 6.83e-06 | 0.00543
24 | DALRD3 | DALR anticodon binding domain containing 3 | 649467 | 6 | 6 | 6 | 0 | 1 | 0 | 2 | 0 | 3 | 0 | 0.000363 | 0.276 | 0.058 | 0.0024 | 0.0027 | 1.45e-05 | 0.0110
25 | NCOR1 | nuclear receptor co-repressor 1 | 3804021 | 17 | 17 | 17 | 1 | 0 | 1 | 1 | 1 | 13 | 1 | 2.70e-06 | 0.128 | 0.51 | 0.22 | 0.41 | 1.64e-05 | 0.0120
26 | AFF2 | AF4/FMR2 family, member 2 | 2066025 | 13 | 13 | 13 | 1 | 2 | 1 | 6 | 1 | 3 | 0 | 4.77e-06 | 0.235 | 0.14 | 0.68 | 0.25 | 1.75e-05 | 0.0123
27 | ERBB2 | v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian) | 1902264 | 8 | 7 | 6 | 1 | 2 | 0 | 3 | 3 | 0 | 0 | 0.00982 | 0.391 | 0.00059 | 0.00072 | 0.00014 | 1.95e-05 | 0.0132
28 | ZFP36L1 | zinc finger protein 36, C3H type-like 1 | 519675 | 7 | 7 | 7 | 0 | 0 | 1 | 1 | 1 | 4 | 0 | 8.32e-06 | 0.305 | 0.073 | 0.91 | 0.17 | 2.08e-05 | 0.0136
29 | GPS2 | G protein pathway suppressor 2 | 518661 | 6 | 6 | 6 | 1 | 0 | 0 | 0 | 0 | 6 | 0 | 3.65e-05 | 0.921 | 0.037 | 0.08 | 0.044 | 2.31e-05 | 0.0146
30 | MYB | v-myb myeloblastosis viral oncogene homolog (avian) | 1177761 | 8 | 8 | 8 | 0 | 1 | 1 | 1 | 1 | 4 | 0 | 6.64e-05 | 0.214 | 0.17 | 0.019 | 0.041 | 3.73e-05 | 0.0227
31 | PRRX1 | paired related homeobox 1 | 402051 | 5 | 5 | 5 | 0 | 3 | 0 | 1 | 0 | 1 | 0 | 0.000612 | 0.121 | 0.13 | 0.0044 | 0.0091 | 7.29e-05 | 0.0430
32 | RPGR | retinitis pigmentosa GTPase regulator | 1930149 | 10 | 10 | 10 | 0 | 1 | 2 | 1 | 0 | 6 | 0 | 4.65e-05 | 0.271 | 0.32 | 0.062 | 0.14 | 8.40e-05 | 0.0480
33 | CDKN1B | cyclin-dependent kinase inhibitor 1B (p27, Kip1) | 272259 | 5 | 5 | 4 | 0 | 0 | 0 | 0 | 0 | 5 | 0 | 2.47e-05 | 0.673 | 0.29 | 0.32 | 0.34 | 0.000106 | 0.0575
34 | AVPI1 | arginine vasopressin-induced 1 | 186069 | 4 | 4 | 3 | 0 | 1 | 0 | 3 | 0 | 0 | 0 | 0.000131 | 0.434 | 0.026 | 0.68 | 0.064 | 0.000107 | 0.0575
35 | GPR32 | G protein-coupled receptor 32 | 544518 | 5 | 5 | 3 | 1 | 1 | 0 | 1 | 3 | 0 | 0 | 0.000654 | 0.636 | 0.0057 | 0.81 | 0.016 | 0.000132 | 0.0689

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 | TP53 | tumor protein p53 | 187 | 308 | 180 | 156156 | 37514 | 0 | 0
2 | PIK3R1 | phosphoinositide-3-kinase, regulatory subunit 1 (alpha) | 14 | 33 | 7 | 16731 | 8 | 4.5e-13 | 6.9e-10
3 | GATA3 | GATA binding protein 3 | 56 | 34 | 21 | 17238 | 155 | 4.6e-13 | 6.9e-10
4 | ERBB2 | v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian) | 8 | 41 | 6 | 20787 | 44 | 1.7e-12 | 1.4e-09
5 | RUNX1 | runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene) | 18 | 175 | 14 | 88725 | 54 | 2.1e-12 | 1.4e-09
6 | PIK3CA | phosphoinositide-3-kinase, catalytic, alpha polypeptide | 194 | 184 | 184 | 93288 | 113646 | 2.2e-12 | 1.4e-09
7 | CDH1 | cadherin 1, type 1, E-cadherin (epithelial) | 33 | 184 | 15 | 93288 | 27 | 2.2e-12 | 1.4e-09
8 | PTEN | phosphatase and tensin homolog (mutated in multiple advanced cancers 1) | 17 | 728 | 17 | 369096 | 712 | 5.8e-12 | 3.3e-09
9 | PTPN22 | protein tyrosine phosphatase, non-receptor type 22 (lymphoid) | 8 | 5 | 2 | 2535 | 2 | 7e-06 | 0.0035
10 | FGFR2 | fibroblast growth factor receptor 2 (bacteria-expressed kinase, keratinocyte growth factor receptor, craniofacial dysostosis 1, Crouzon syndrome, Pfeiffer syndrome, Jackson-Weiss syndrome) | 4 | 49 | 3 | 24843 | 15 | 8.1e-06 | 0.0036

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
--- | --- | --- | --- | --- | --- | --- | --- | --- | --- | ---
6944 | PIK3CA | phosphoinositide-3-kinase, catalytic, alpha polypeptide | 194 | 0 | 4345 | 5558 | 5984 | 4345 | 5558 | 5984
9414 | TP53 | tumor protein p53 | 187 | 0 | 237 | 643 | 1330 | 237 | 643 | 1330
311 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | 12 | 0 | 55 | 55 | 55 | 55 | 55 | 55
8171 | SF3B1 | splicing factor 3b, subunit 1, 155kDa | 10 | 0 | 10 | 10 | 10 | 10 | 10 | 10
6285 | OBSCN | obscurin, cytoskeletal calmodulin and titin-interacting RhoGEF | 27 | 0 | 7 | 7 | 8 | 7 | 7 | 8
9873 | VASN | vasorin | 6 | 0 | 6 | 6 | 6 | 6 | 6 | 6
1755 | CDH1 | cadherin 1, type 1, E-cadherin (epithelial) | 33 | 0 | 5 | 5 | 6 | 5 | 5 | 6
2275 | CTCF | CCCTC-binding factor (zinc finger protein) | 13 | 0 | 3 | 7 | 7 | 3 | 7 | 7
3858 | GPR32 | G protein-coupled receptor 32 | 5 | 0 | 3 | 4 | 4 | 3 | 4 | 4
3009 | ERBB2 | v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian) | 8 | 0 | 3 | 3 | 4 | 3 | 3 | 4

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: 115. 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 | HSA04210_APOPTOSIS | Genes involved in apoptosis | AIFM1, AKT1, AKT2, AKT3, APAF1, ATM, BAD, BAX, BCL2, BCL2L1, BID, BIRC2, BIRC3, BIRC4, CAPN1, CAPN2, CASP10, CASP3, CASP6, CASP7, CASP8, CASP9, CFLAR, CHP, CHUK, CSF2RB, CYCS, DFFA, DFFB, ENDOG, FADD, FAS, FASLG, IKBKB, IKBKG, IL1A, IL1B, IL1R1, IL1RAP, IL3, IL3RA, IRAK1, IRAK2, IRAK3, IRAK4, MAP3K14, MYD88, NFKB1, NFKB2, NFKBIA, NGFB, NTRK1, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PPP3CA, PPP3CB, PPP3CC, PPP3R1, PPP3R2, PRKACA, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, RELA, RIPK1, TNF, TNFRSF10A, TNFRSF10B, TNFRSF10C, TNFRSF10D, TNFRSF1A, TNFSF10, TP53, TRADD, TRAF2 | 81 | AKT1(12), AKT2(1), AKT3(3), APAF1(1), ATM(12), BAD(1), BID(4), CAPN1(3), CAPN2(2), CASP6(2), CASP8(3), CSF2RB(2), DFFB(2), FAS(1), FASLG(1), IKBKB(3), IL1A(1), IL1R1(1), IL1RAP(2), IL3RA(1), IRAK1(1), IRAK2(3), IRAK3(1), IRAK4(2), NFKB1(1), NFKB2(3), NFKBIA(1), NTRK1(3), PIK3CA(194), PIK3CB(4), PIK3CG(2), PIK3R1(14), PIK3R3(1), PPP3CA(3), PPP3CB(3), PRKACA(1), PRKAR1A(1), PRKAR2A(1), PRKAR2B(1), RELA(1), RIPK1(3), TNFRSF10D(1), TNFRSF1A(1), TP53(187) | 64465557 | 491 | 359 | 244 | 28 | 43 | 129 | 50 | 162 | 106 | 1 | <1.00e-15 | <1.00e-15 | <1.43e-14
2 | ARFPATHWAY | Cyclin-dependent kinase inhibitor 2A is a tumor suppressor that induces G1 arrest and can activate the p53 pathway, leading to G2/M arrest. | ABL1, CDKN2A, E2F1, MDM2, MYC, PIK3CA, PIK3R1, POLR1A, POLR1B, POLR1C, POLR1D, RAC1, RB1, TBX2, TP53, TWIST1 | 16 | ABL1(4), E2F1(2), MDM2(2), MYC(1), PIK3CA(194), PIK3R1(14), POLR1A(2), POLR1B(2), POLR1C(2), POLR1D(2), RB1(10), TP53(187) | 14816568 | 422 | 334 | 185 | 11 | 35 | 97 | 37 | 151 | 102 | 0 | <1.00e-15 | <1.00e-15 | <1.43e-14
3 | 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 | 99 | AKT1(12), AKT2(1), AKT3(3), CASP8(3), CD14(1), CD40(1), CD86(2), IFNA1(1), IFNA10(1), IFNA13(1), IFNA14(2), IFNA16(1), IFNA2(2), IFNA4(1), IFNA7(1), IFNAR1(1), IFNAR2(1), IFNB1(1), IKBKB(3), IKBKE(1), IL12A(1), IL12B(1), IL6(2), IRAK1(1), IRAK4(2), IRF3(2), JUN(1), LBP(1), MAP2K1(1), MAP2K2(1), MAP2K3(1), MAP2K4(20), MAP2K7(1), MAP3K7(1), MAP3K8(2), MAPK1(1), MAPK10(1), MAPK14(1), MAPK3(1), MAPK8(2), NFKB1(1), NFKB2(3), NFKBIA(1), PIK3CA(194), PIK3CB(4), PIK3CG(2), PIK3R1(14), PIK3R3(1), RELA(1), RIPK1(3), SPP1(2), STAT1(1), TBK1(1), TICAM1(2), TIRAP(2), TLR1(1), TLR2(1), TLR3(1), TLR4(8), TLR5(1), TLR7(5), TLR8(3), TLR9(1), TRAF3(1), TRAF6(2) | 67859415 | 340 | 267 | 165 | 40 | 20 | 108 | 32 | 126 | 53 | 1 | 1.50e-13 | <1.00e-15 | <1.43e-14
4 | ST_JNK_MAPK_PATHWAY | JNKs are MAP kinases regulated by several levels of kinases (MAPKK, MAPKKK) and phosphorylate transcription factors and regulatory proteins. | AKT1, ATF2, CDC42, DLD, DUSP10, DUSP4, DUSP8, GAB1, GADD45A, GCK, IL1R1, JUN, MAP2K4, MAP2K5, MAP2K7, MAP3K1, MAP3K10, MAP3K11, MAP3K12, MAP3K13, MAP3K2, MAP3K3, MAP3K4, MAP3K5, MAP3K7, MAP3K7IP1, MAP3K7IP2, MAP3K9, MAPK10, MAPK7, MAPK8, MAPK9, MYEF2, NFATC3, NR2C2, PAPPA, SHC1, TP53, TRAF6, ZAK | 38 | AKT1(12), ATF2(2), DLD(1), DUSP10(1), DUSP4(1), GAB1(1), GCK(2), IL1R1(1), JUN(1), MAP2K4(20), MAP2K5(2), MAP2K7(1), MAP3K1(46), MAP3K10(4), MAP3K11(1), MAP3K12(2), MAP3K13(5), MAP3K4(4), MAP3K5(2), MAP3K7(1), MAP3K9(3), MAPK10(1), MAPK8(2), MYEF2(2), NFATC3(3), NR2C2(1), PAPPA(4), SHC1(1), TP53(187), TRAF6(2), ZAK(1) | 38087868 | 317 | 263 | 230 | 21 | 42 | 46 | 38 | 51 | 125 | 15 | 4.52e-13 | <1.00e-15 | <1.43e-14
5 | SIG_PIP3_SIGNALING_IN_CARDIAC_MYOCTES | Genes related to PIP3 signaling in cardiac myocytes | AKT1, AKT2, AKT3, BAD, BCL2L1, CDC42, CDK2, CDKN1B, CDKN2A, CREB1, CREB3, CREB5, EBP, ERBB4, F2RL2, FOXO3A, FRAP1, GAB1, GADD45A, GRB2, GSK3A, GSK3B, IFI27, IGF1, IGFBP1, INPPL1, IRS1, IRS2, IRS4, MET, MYC, NOLC1, P101-PI3K, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PARD3, PARD6A, PDK1, PIK3CA, PIK3CD, PPP1R13B, PREX1, PSCD3, PTEN, PTK2, PTPN1, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KB1, SFN, SHC1, SLC2A4, SOS1, SOS2, TSC1, TSC2, YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ, YWHAZ | 62 | AKT1(12), AKT2(1), AKT3(3), BAD(1), CDK2(1), CDKN1B(5), CREB1(1), CREB3(1), EBP(1), ERBB4(6), F2RL2(1), GAB1(1), GRB2(1), GSK3A(1), IGF1(1), INPPL1(2), IRS1(1), IRS4(4), MET(5), MYC(1), NOLC1(2), PAK1(2), PAK2(1), PAK3(2), PAK6(1), PAK7(1), PARD3(3), PDK1(1), PIK3CA(194), PPP1R13B(2), PREX1(8), PTEN(17), PTK2(3), RPS6KA1(1), RPS6KA2(2), RPS6KA3(2), SHC1(1), SLC2A4(1), SOS1(4), SOS2(2), TSC1(3), TSC2(2), YWHAB(1) | 57138393 | 306 | 247 | 132 | 28 | 18 | 98 | 38 | 117 | 34 | 1 | 2.78e-15 | <1.00e-15 | <1.43e-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(1), CD3G(1), ELK1(2), GRB2(1), JUN(1), LAT(1), MAP2K1(1), MAP2K4(20), MAP3K1(46), MAPK3(1), MAPK8(2), NFATC1(1), NFATC2(1), NFATC3(3), NFATC4(3), NFKB1(1), NFKBIA(1), PIK3CA(194), PIK3R1(14), PLCG1(5), PPP3CA(3), PPP3CB(3), PTPN7(2), RAF1(1), RASA1(2), RELA(1), SHC1(1), SOS1(4), VAV1(2), ZAP70(1) | 35946807 | 320 | 241 | 155 | 21 | 15 | 85 | 26 | 119 | 60 | 15 | <1.00e-15 | <1.00e-15 | <1.43e-14
7 | ST_B_CELL_ANTIGEN_RECEPTOR | B cell receptors bind antigens and promote B cell activation. | AKT1, AKT2, AKT3, BAD, BCR, BLNK, BTK, CD19, CSK, DAG1, EPHB2, GRB2, ITPKA, ITPKB, LYN, MAP2K1, MAP2K2, MAPK1, NFAT5, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, NFKBIL1, NFKBIL2, PAG, PI3, PIK3CA, PIK3CD, PIK3R1, PLCG2, PPP1R13B, RAF1, SERPINA4, SHC1, SOS1, SOS2, SYK, VAV1 | 38 | AKT1(12), AKT2(1), AKT3(3), BAD(1), BCR(1), BLNK(1), BTK(3), CD19(2), DAG1(1), EPHB2(2), GRB2(1), ITPKA(1), ITPKB(8), LYN(4), MAP2K1(1), MAP2K2(1), MAPK1(1), NFAT5(3), NFKB1(1), NFKB2(3), NFKBIA(1), NFKBIE(1), PI3(1), PIK3CA(194), PIK3R1(14), PLCG2(2), PPP1R13B(2), RAF1(1), SERPINA4(3), SHC1(1), SOS1(4), SOS2(2), SYK(2), VAV1(2) | 39742716 | 281 | 240 | 108 | 15 | 18 | 96 | 25 | 115 | 26 | 1 | <1.00e-15 | <1.00e-15 | <1.43e-14
8 | 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(12), AKT2(1), AKT3(3), BRAF(3), EIF4B(1), FIGF(2), HIF1A(1), IGF1(1), MAPK1(1), MAPK3(1), PIK3CA(194), PIK3CB(4), PIK3CG(2), PIK3R1(14), PIK3R3(1), PRKAA1(1), PRKAA2(3), RHEB(1), RICTOR(3), RPS6(2), RPS6KA1(1), RPS6KA2(2), RPS6KA3(2), RPS6KA6(3), RPS6KB2(4), TSC1(3), TSC2(2), ULK1(2), ULK2(1) | 41043171 | 271 | 234 | 98 | 23 | 11 | 96 | 24 | 117 | 23 | 0 | 5.11e-15 | <1.00e-15 | <1.43e-14
9 | 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 | 52 | ACTA1(1), AGT(3), AKT1(12), CALR(1), CAMK1(2), CAMK1G(1), CREBBP(2), EDN1(2), F2(3), HAND2(2), IGF1(1), LIF(3), MAP2K1(1), MAPK1(1), MAPK14(1), MAPK3(1), MAPK8(2), MEF2C(2), MYH2(2), NFATC1(1), NFATC2(1), NFATC3(3), NFATC4(3), NPPA(1), PIK3CA(194), PIK3R1(14), PPP3CA(3), PPP3CB(3), PRKAR1A(1), PRKAR2A(1), PRKAR2B(1), RAF1(1) | 38119302 | 270 | 232 | 97 | 24 | 7 | 90 | 33 | 119 | 21 | 0 | 4.46e-14 | <1.00e-15 | <1.43e-14
10 | ST_DIFFERENTIATION_PATHWAY_IN_PC12_CELLS | Rat-derived PC12 cells respond to nerve growth factor (NGF) and PACAP to differentiate into neuronal cells. | AKT1, ASAH1, ATF1, BRAF, CAMP, CREB1, CREB3, CREB5, CREBBP, CRKL, DAG1, EGR1, EGR2, EGR3, EGR4, ELK1, FRS2, GAS, GNAQ, GRF2, JUN, MAP1B, MAP2K4, MAP2K7, MAPK1, MAPK10, MAPK3, MAPK8, MAPK8IP1, MAPK8IP2, MAPK8IP3, MAPK9, NTRK1, OPN1LW, PACAP, PIK3C2G, PIK3CA, PIK3CD, PIK3R1, PTPN11, RPS6KA3, SH2B, SHC1, SRC, TERF2IP, TH, TUBA3 | 42 | AKT1(12), ASAH1(1), BRAF(3), CREB1(1), CREB3(1), CREBBP(2), CRKL(1), DAG1(1), EGR1(1), EGR2(1), EGR3(3), ELK1(2), GNAQ(1), JUN(1), MAP1B(1), MAP2K4(20), MAP2K7(1), MAPK1(1), MAPK10(1), MAPK3(1), MAPK8(2), MAPK8IP1(1), MAPK8IP2(2), MAPK8IP3(4), NTRK1(3), OPN1LW(1), PIK3C2G(2), PIK3CA(194), PIK3R1(14), PTPN11(1), RPS6KA3(2), SHC1(1), TERF2IP(2) | 39579462 | 285 | 232 | 111 | 18 | 15 | 90 | 25 | 116 | 39 | 0 | <1.00e-15 | <1.00e-15 | <1.43e-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 | EOSINOPHILSPATHWAY | Recruitment of eosinophils in the inflammatory response observed in asthma occurs via the chemoattractant eotaxin binding to the CCR3 receptor. | CCL11, CCL5, CCR3, CSF2, HLA-DRA, HLA-DRB1, IL3, IL5 | 7 | CCL11(1), CCR3(1), HLA-DRB1(4) | 1828749 | 6 | 6 | 6 | 1 | 0 | 1 | 1 | 2 | 2 | 0 | 0.43 | 0.017 | 1
2 | STILBENE_COUMARINE_AND_LIGNIN_BIOSYNTHESIS |  | EPX, GBA3, LPO, MPO, PRDX1, PRDX2, PRDX5, PRDX6, TPO, TYR | 10 | EPX(1), LPO(5), MPO(2), PRDX1(1), PRDX5(1), TPO(6), TYR(4) | 7428057 | 20 | 20 | 20 | 2 | 6 | 2 | 5 | 3 | 4 | 0 | 0.067 | 0.019 | 1
3 | ST_PAC1_RECEPTOR_PATHWAY | The signaling peptide PACAP binds to its receptor, PAC1R, which activates adenylyl cyclase and phospholipase C. | ASAH1, CAMP, DAG1, GAS, GNAQ, ITPKA, ITPKB, PACAP | 6 | ASAH1(1), DAG1(1), GNAQ(1), ITPKA(1), ITPKB(8) | 4432701 | 12 | 12 | 12 | 0 | 2 | 1 | 3 | 4 | 2 | 0 | 0.04 | 0.023 | 1
4 | HSA00601_GLYCOSPHINGOLIPID_BIOSYNTHESIS_LACTOSERIES | Genes involved in glycosphingolipid biosynthesis - lactoseries | ABO, B3GALT1, B3GALT2, B3GALT5, B3GNT5, FUT1, FUT2, FUT3, ST3GAL3, ST3GAL4 | 10 | ABO(4), B3GALT1(1), B3GALT2(1), B3GALT5(1), FUT2(2), FUT3(4), ST3GAL3(1), ST3GAL4(1) | 5407662 | 15 | 15 | 14 | 2 | 4 | 5 | 2 | 2 | 2 | 0 | 0.05 | 0.034 | 1
5 | 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(1), FSHR(4), GNAS(5), XPO1(3) | 6833346 | 18 | 18 | 18 | 2 | 4 | 4 | 3 | 5 | 2 | 0 | 0.13 | 0.043 | 1
6 | BLOOD_GROUP_GLYCOLIPID_BIOSYNTHESIS_LACTOSERIES |  | ABO, FUT1, FUT2, FUT3, FUT5, FUT6, SIAT6, ST3GAL3 | 7 | ABO(4), FUT2(2), FUT3(4), FUT5(1), ST3GAL3(1) | 3810105 | 12 | 12 | 11 | 2 | 4 | 3 | 1 | 2 | 2 | 0 | 0.096 | 0.065 | 1
7 | HSA00940_PHENYLPROPANOID_BIOSYNTHESIS | Genes involved in phenylpropanoid biosynthesis | EPX, GBA, GBA3, LPO, MPO, PRDX6, TPO | 7 | EPX(1), LPO(5), MPO(2), TPO(6) | 6402396 | 14 | 14 | 14 | 0 | 6 | 1 | 2 | 2 | 3 | 0 | 0.012 | 0.081 | 1
8 | INOSITOL_METABOLISM |  | ALDH6A1, ALDOA, ALDOB, ALDOC, TPI1 | 5 | ALDOA(4), ALDOB(2), TPI1(2) | 2928939 | 8 | 8 | 8 | 0 | 0 | 4 | 3 | 0 | 1 | 0 | 0.051 | 0.088 | 1
9 | METHIONINEPATHWAY | Catabolic Pathways for Methionine, Isoleucine, Threonine and Valine | BCKDHB, BCKDK, CBS, CTH, MUT | 5 | BCKDK(2), CBS(2), CTH(3), MUT(1) | 3739125 | 8 | 8 | 8 | 0 | 1 | 1 | 1 | 1 | 4 | 0 | 0.14 | 0.12 | 1
10 | SA_DIACYLGLYCEROL_SIGNALING | DAG (diacylglycerol) signaling activity | ESR1, ESR2, ITPKA, PDE1A, PDE1B, PLCB1, PLCB2, PRL, TRH, VIP | 10 | ESR1(2), ESR2(2), ITPKA(1), PDE1A(2), PDE1B(2), PLCB1(4), PLCB2(2), VIP(1) | 8374626 | 16 | 16 | 16 | 2 | 2 | 6 | 3 | 3 | 2 | 0 | 0.12 | 0.16 | 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.

- Analysis Results (MD5 checksum)

- Auxiliary Data (MD5 checksum)

- MAGE-TAB File (MD5 checksum)

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