Uterine Corpus Endometrioid 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: UCEC

- 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.final_analysis_set.maf

- Significantly mutated genes (q ≤ 0.1): 82

- Mutations seen in COSMIC: 1008

- Significantly mutated genes in COSMIC territory: 47

- Genes with clustered mutations (≤ 3 aa apart): 4501

- Significantly mutated genesets: 69

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

Mutation Preprocessing

- Read 248 MAFs of type "WashU"

- Total number of mutations in input MAFs: 184824

- After removing 118 mutations outside chr1-24: 184706

- After removing 1940 noncoding mutations: 182766

- After collapsing adjacent/redundant mutations: 182636

Mutation Filtering

- Number of mutations before filtering: 182636

- After removing 8680 mutations outside gene set: 173956

- After removing 1038 mutations outside category set: 172918

Results
Breakdown of Mutations by Type

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

type | count
--- | ---
Frame_Shift_Del | 1070
Frame_Shift_Ins | 474
In_Frame_Del | 765
In_Frame_Ins | 148
Missense_Mutation | 115613
Nonsense_Mutation | 11935
Nonstop_Mutation | 138
Silent | 40121
Splice_Site | 2654
Total | 172918

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 | 38721 | 409266464 | 0.000095 | 95 | 5.4 | 2.1
*Cp(A/C/T)->mut | 51454 | 3453658664 | 0.000015 | 15 | 0.85 | 3.3
A->mut | 24344 | 3744388816 | 6.5e-06 | 6.5 | 0.37 | 3.9
*CpG->(G/A) | 1084 | 409266464 | 2.6e-06 | 2.6 | 0.15 | 2.7
indel+null | 16310 | 7607313944 | 2.1e-06 | 2.1 | 0.12 | NaN
double_null | 884 | 7607313944 | 1.2e-07 | 0.12 | 0.0067 | NaN
Total | 132797 | 7607313944 | 0.000017 | 17 | 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: UCEC.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)->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_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: 82. 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 | PTEN | phosphatase and tensin homolog (mutated in multiple advanced cancers 1) | 309504 | 227 | 161 | 134 | 5 | 19 | 29 | 21 | 33 | 98 | 27 | 1.11e-15 | 4.9e-12 | 2e-07 | 0.71 | 0.000023 | 0.000 | 0.000
2 | FBXW7 | F-box and WD repeat domain containing 7 | 640832 | 46 | 39 | 30 | 1 | 22 | 12 | 2 | 1 | 8 | 1 | 3.77e-15 | 0.00048 | 0.00054 | 0.0046 | 0.00011 | 0.000 | 0.000
3 | SPOP | speckle-type POZ protein | 287928 | 23 | 21 | 18 | 0 | 5 | 8 | 6 | 0 | 4 | 0 | 5.66e-15 | 0.0041 | 0.0029 | 0.022 | 0.00068 | 1.11e-16 | 6.77e-13
4 | CTCF | CCCTC-binding factor (zinc finger protein) | 551552 | 49 | 45 | 39 | 1 | 8 | 4 | 7 | 0 | 28 | 2 | 1.89e-15 | 0.00095 | 0.0061 | 0.052 | 0.0059 | 4.44e-16 | 1.31e-12
5 | PIK3CA | phosphoinositide-3-kinase, catalytic, alpha polypeptide | 815176 | 172 | 132 | 76 | 3 | 31 | 61 | 68 | 3 | 9 | 0 | <1.00e-15 | 2.1e-11 | 2e-07 | 2e-07 | 0 | <1.00e-15 | <1.31e-12
6 | PIK3R1 | phosphoinositide-3-kinase, regulatory subunit 1 (alpha) | 585280 | 100 | 83 | 77 | 2 | 4 | 4 | 13 | 1 | 63 | 15 | 6.00e-15 | 0.0021 | 2e-07 | 0.38 | 0 | <1.00e-15 | <1.31e-12
7 | CTNNB1 | catenin (cadherin-associated protein), beta 1, 88kDa | 595696 | 80 | 74 | 25 | 7 | 5 | 61 | 14 | 0 | 0 | 0 | <1.00e-15 | 0.0034 | 2e-07 | 2e-07 | 0 | <1.00e-15 | <1.31e-12
8 | TP53 | tumor protein p53 | 317688 | 74 | 69 | 50 | 2 | 23 | 18 | 15 | 1 | 17 | 0 | 1.55e-15 | 2.8e-06 | 2e-07 | 2e-07 | 0 | <1.00e-15 | <1.31e-12
9 | KRAS | v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog | 175336 | 53 | 53 | 12 | 1 | 2 | 46 | 4 | 1 | 0 | 0 | 3.44e-15 | 0.0012 | 2e-07 | 0.00023 | 0 | <1.00e-15 | <1.31e-12
10 | PPP2R1A | protein phosphatase 2 (formerly 2A), regulatory subunit A , alpha isoform | 453840 | 30 | 27 | 18 | 3 | 10 | 17 | 1 | 0 | 2 | 0 | 6.38e-14 | 0.0023 | 2e-07 | 0.098 | 0 | <1.00e-15 | <1.31e-12
11 | PRKAR1B | protein kinase, cAMP-dependent, regulatory, type I, beta | 286192 | 4 | 4 | 4 | 3 | 2 | 0 | 0 | 1 | 1 | 0 | 0.993 | 0.82 | 0.0055 | 6.6e-06 | 0 | <1.00e-15 | <1.31e-12
12 | HMGN1 | high-mobility group nucleosome binding domain 1 | 76384 | 2 | 2 | 2 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0.178 | 0.67 | 0.1 | 0.0047 | 0 | <1.00e-15 | <1.31e-12
13 | IL10 | interleukin 10 | 138136 | 3 | 2 | 3 | 3 | 1 | 1 | 0 | 0 | 1 | 0 | 0.709 | 0.98 | 0.14 | 0.0046 | 0 | <1.00e-15 | <1.31e-12
14 | NMD3 | NMD3 homolog (S. cerevisiae) | 389856 | 2 | 2 | 2 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0.949 | 0.63 | 0.27 | 0.081 | 0 | <1.00e-15 | <1.31e-12
15 | FGFR2 | fibroblast growth factor receptor 2 (bacteria-expressed kinase, keratinocyte growth factor receptor, craniofacial dysostosis 1, Crouzon syndrome, Pfeiffer syndrome, Jackson-Weiss syndrome) | 691920 | 34 | 31 | 19 | 3 | 3 | 5 | 13 | 9 | 3 | 1 | 6.77e-15 | 0.0097 | 0.018 | 0.24 | 0.031 | 7.77e-15 | 9.47e-12
16 | ARID1A | AT rich interactive domain 1A (SWI-like) | 1428976 | 94 | 83 | 79 | 5 | 2 | 7 | 5 | 1 | 65 | 14 | 1.78e-15 | 0.00014 | 0.17 | 0.42 | 0.3 | 1.90e-14 | 2.17e-11
17 | CHD4 | chromodomain helicase DNA binding protein 4 | 1460720 | 43 | 35 | 38 | 2 | 16 | 16 | 8 | 0 | 2 | 1 | 1.55e-11 | 0.0046 | 0.011 | 0.55 | 0.022 | 1.02e-11 | 1.10e-08
18 | NFE2L2 | nuclear factor (erythroid-derived 2)-like 2 | 449872 | 15 | 15 | 12 | 0 | 2 | 3 | 5 | 3 | 2 | 0 | 2.78e-08 | 0.016 | 0.000068 | 0.028 | 0.000025 | 1.98e-11 | 2.01e-08
19 | P2RY11 | purinergic receptor P2Y, G-protein coupled, 11 | 5704 | 9 | 9 | 9 | 3 | 3 | 4 | 0 | 1 | 1 | 0 | 2.23e-11 | 0.3 | NaN | NaN | NaN | 2.23e-11 | 2.15e-08
20 | CCND1 | cyclin D1 | 222952 | 15 | 15 | 13 | 1 | 1 | 7 | 3 | 0 | 4 | 0 | 7.63e-09 | 0.084 | 0.00013 | 0.23 | 0.00022 | 4.65e-11 | 4.25e-08
21 | SOX17 | SRY (sex determining region Y)-box 17 | 91512 | 7 | 7 | 3 | 0 | 0 | 6 | 0 | 0 | 1 | 0 | 4.35e-07 | 0.15 | 0.0048 | 0.013 | 0.00078 | 7.78e-09 | 6.78e-06
22 | FOXA2 | forkhead box A2 | 227912 | 12 | 12 | 12 | 1 | 1 | 3 | 2 | 0 | 6 | 0 | 3.75e-08 | 0.27 | 0.097 | 0.11 | 0.086 | 6.63e-08 | 5.51e-05
23 | FAM9A | family with sequence similarity 9, member A | 255688 | 20 | 14 | 20 | 1 | 2 | 12 | 1 | 0 | 4 | 1 | 7.46e-08 | 0.096 | 0.1 | 1 | 0.21 | 3.03e-07 | 0.000241
24 | DNER | delta/notch-like EGF repeat containing | 492528 | 21 | 18 | 20 | 1 | 4 | 9 | 5 | 0 | 3 | 0 | 0.000159 | 0.01 | 0.043 | 0.0001 | 0.00032 | 8.99e-07 | 0.000685
25 | SMTNL2 | smoothelin-like 2 | 223944 | 9 | 9 | 3 | 2 | 0 | 2 | 0 | 0 | 7 | 0 | 0.00174 | 0.37 | 6.6e-06 | 0.48 | 0.000058 | 1.72e-06 | 0.00125
26 | RBMX | RNA binding motif protein, X-linked | 313224 | 14 | 13 | 8 | 0 | 1 | 4 | 2 | 0 | 7 | 0 | 2.89e-05 | 0.3 | 0.0044 | 0.15 | 0.0042 | 2.05e-06 | 0.00144
27 | PGR | progesterone receptor | 393328 | 13 | 12 | 11 | 2 | 3 | 3 | 2 | 1 | 4 | 0 | 0.00771 | 0.33 | 0.00026 | 0.00072 | 0.000023 | 2.98e-06 | 0.00202
28 | TNFAIP6 | tumor necrosis factor, alpha-induced protein 6 | 212784 | 12 | 12 | 8 | 0 | 2 | 4 | 0 | 0 | 6 | 0 | 3.44e-06 | 0.18 | 0.21 | 0.97 | 0.3 | 1.54e-05 | 0.0101
29 | SGK1 | serum/glucocorticoid regulated kinase 1 | 480376 | 16 | 15 | 14 | 3 | 2 | 5 | 1 | 1 | 7 | 0 | 0.000234 | 0.52 | 0.49 | 0.0012 | 0.0048 | 1.65e-05 | 0.0104
30 | PDE8B | phosphodiesterase 8B | 595944 | 19 | 16 | 19 | 1 | 7 | 5 | 6 | 0 | 1 | 0 | 0.0265 | 0.018 | 0.0035 | 0.00022 | 0.000047 | 1.81e-05 | 0.0110
31 | HPD | 4-hydroxyphenylpyruvate dioxygenase | 307024 | 7 | 7 | 3 | 0 | 0 | 0 | 1 | 0 | 6 | 0 | 0.0315 | 0.64 | 0.0069 | 0.00018 | 0.000057 | 2.55e-05 | 0.0149
32 | RPL14 | ribosomal protein L14 | 168392 | 8 | 7 | 4 | 0 | 0 | 1 | 0 | 2 | 5 | 0 | 0.000151 | 0.36 | 0.0064 | 0.94 | 0.012 | 2.60e-05 | 0.0149
33 | TAP1 | transporter 1, ATP-binding cassette, sub-family B (MDR/TAP) | 150784 | 8 | 8 | 8 | 0 | 2 | 3 | 0 | 0 | 3 | 0 | 0.00403 | 0.12 | 0.00035 | 0.12 | 0.0005 | 2.85e-05 | 0.0158
34 | MAX | MYC associated factor X | 209064 | 12 | 11 | 8 | 0 | 3 | 3 | 5 | 0 | 1 | 0 | 1.23e-05 | 0.048 | 0.26 | 0.065 | 0.17 | 2.97e-05 | 0.0160
35 | ZNF286A | zinc finger protein 286A | 393328 | 16 | 12 | 14 | 1 | 3 | 6 | 6 | 0 | 1 | 0 | 0.00104 | 0.12 | 0.0012 | 0.59 | 0.0027 | 3.85e-05 | 0.0201

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: 47. 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) | 227 | 728 | 218 | 180544 | 14940 | 0 | 0
2 | PIK3R1 | phosphoinositide-3-kinase, regulatory subunit 1 (alpha) | 100 | 33 | 39 | 8184 | 111 | 2.5e-13 | 4e-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 | 49 | 24 | 12152 | 113 | 3.4e-13 | 4e-10
4 | KRAS | v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog | 53 | 51 | 49 | 12648 | 556649 | 3.5e-13 | 4e-10
5 | FBXW7 | F-box and WD repeat domain containing 7 | 46 | 91 | 29 | 22568 | 852 | 5.3e-13 | 4e-10
6 | CTNNB1 | catenin (cadherin-associated protein), beta 1, 88kDa | 80 | 101 | 67 | 25048 | 23813 | 5.6e-13 | 4e-10
7 | TP53 | tumor protein p53 | 74 | 308 | 72 | 76384 | 24186 | 7e-13 | 4e-10
8 | PIK3CA | phosphoinositide-3-kinase, catalytic, alpha polypeptide | 172 | 184 | 150 | 45632 | 35669 | 7.2e-13 | 4e-10
9 | NRAS | neuroblastoma RAS viral (v-ras) oncogene homolog | 9 | 28 | 6 | 6944 | 6490 | 4e-09 | 2e-06
10 | RB1 | retinoblastoma 1 (including osteosarcoma) | 26 | 267 | 11 | 66216 | 30 | 4.3e-08 | 0.000019

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
--- | --- | --- | --- | --- | --- | --- | --- | --- | --- | ---
11548 | PTEN | phosphatase and tensin homolog (mutated in multiple advanced cancers 1) | 226 | 0 | 1515 | 1989 | 2858 | 1515 | 1989 | 2858
7589 | KRAS | v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog | 52 | 0 | 661 | 949 | 994 | 661 | 949 | 994
10791 | PIK3CA | phosphoinositide-3-kinase, catalytic, alpha polypeptide | 172 | 0 | 573 | 1075 | 1553 | 573 | 1075 | 1553
3515 | CTNNB1 | catenin (cadherin-associated protein), beta 1, 88kDa | 80 | 0 | 434 | 1165 | 2176 | 434 | 1165 | 2176
14926 | TP53 | tumor protein p53 | 74 | 0 | 89 | 167 | 417 | 89 | 167 | 417
5242 | FGFR2 | fibroblast growth factor receptor 2 (bacteria-expressed kinase, keratinocyte growth factor receptor, craniofacial dysostosis 1, Crouzon syndrome, Pfeiffer syndrome, Jackson-Weiss syndrome) | 34 | 0 | 56 | 56 | 78 | 56 | 56 | 78
5153 | FBXW7 | F-box and WD repeat domain containing 7 | 46 | 0 | 50 | 53 | 68 | 50 | 53 | 68
11060 | POLE | polymerase (DNA directed), epsilon | 47 | 0 | 39 | 42 | 60 | 39 | 42 | 60
11230 | PPP2R1A | protein phosphatase 2 (formerly 2A), regulatory subunit A , alpha isoform | 30 | 0 | 37 | 48 | 77 | 37 | 48 | 77
15262 | TTN | titin | 524 | 0 | 35 | 53 | 103 | 35 | 53 | 103

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: 69. 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 | 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(8), CDKN2A(2), E2F1(9), MDM2(4), MYC(8), PIK3CA(172), PIK3R1(100), POLR1A(16), POLR1B(16), POLR1C(2), POLR1D(3), RAC1(1), RB1(26), TBX2(2), TP53(74), TWIST1(1) | 7247552 | 444 | 223 | 300 | 50 | 87 | 115 | 119 | 6 | 99 | 18 | 3.94e-10 | <1.00e-15 | <3.99e-14
2 | MTORPATHWAY | Mammalian target of rapamycin (mTOR) senses mitogenic factors and nutrients, including ATP, and induces cell proliferation. | AKT1, EIF3S10, EIF4A1, EIF4A2, EIF4B, EIF4E, EIF4EBP1, EIF4G1, EIF4G2, EIF4G3, FKBP1A, FRAP1, MKNK1, PDK2, PDPK1, PIK3CA, PIK3R1, PPP2CA, PTEN, RPS6, RPS6KB1, TSC1, TSC2 | 21 | AKT1(4), EIF4A1(5), EIF4A2(9), EIF4B(7), EIF4E(2), EIF4G1(15), EIF4G2(7), EIF4G3(24), FKBP1A(1), MKNK1(3), PDK2(5), PDPK1(3), PIK3CA(172), PIK3R1(100), PPP2CA(6), PTEN(227), RPS6(7), RPS6KB1(5), TSC1(13), TSC2(15) | 10458408 | 630 | 218 | 417 | 44 | 90 | 141 | 126 | 38 | 191 | 44 | <1.00e-15 | <1.00e-15 | <3.99e-14
3 | IGF1MTORPATHWAY | Growth factor IGF-1 activates AKT, Gsk3-beta, and mTOR to promote muscle hypertrophy. | AKT1, EIF2B5, EIF2S1, EIF2S2, EIF2S3, EIF4E, EIF4EBP1, FRAP1, GSK3B, IGF1, IGF1R, INPPL1, PDK2, PDPK1, PIK3CA, PIK3R1, PPP2CA, PTEN, RPS6, RPS6KB1 | 19 | AKT1(4), EIF2B5(5), EIF2S1(2), EIF2S2(9), EIF2S3(6), EIF4E(2), GSK3B(13), IGF1(5), IGF1R(13), INPPL1(19), PDK2(5), PDPK1(3), PIK3CA(172), PIK3R1(100), PPP2CA(6), PTEN(227), RPS6(7), RPS6KB1(5) | 7335096 | 603 | 217 | 388 | 46 | 79 | 131 | 117 | 40 | 194 | 42 | <1.00e-15 | <1.00e-15 | <3.99e-14
4 | SIG_INSULIN_RECEPTOR_PATHWAY_IN_CARDIAC_MYOCYTES | Genes related to the insulin receptor pathway | AKT1, AKT2, AKT3, BRD4, CAP1, CBL, CDC42, CDKN2A, F2RL2, FLOT1, FLOT2, FOXO1A, GRB2, GSK3A, GSK3B, IGFBP1, INPPL1, IRS1, IRS2, IRS4, LNPEP, MAPK1, MAPK3, PARD3, PARD6A, PDK1, PIK3CA, PIK3CD, PIK3R1, PPYR1, PSCD3, PTEN, PTPN1, RAF1, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KB1, SERPINB6, SFN, SHC1, SLC2A4, SORBS1, SOS1, SOS2, YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ, YWHAZ | 47 | AKT1(4), AKT2(6), AKT3(11), BRD4(10), CAP1(7), CBL(12), CDC42(4), CDKN2A(2), F2RL2(2), FLOT2(2), GRB2(3), GSK3A(10), GSK3B(13), IGFBP1(4), INPPL1(19), IRS1(13), IRS4(21), LNPEP(10), MAPK1(2), MAPK3(3), PARD3(19), PDK1(2), PIK3CA(172), PIK3CD(12), PIK3R1(100), PPYR1(8), PTEN(227), PTPN1(5), RAF1(8), RPS6KA1(1), RPS6KA2(14), RPS6KA3(19), RPS6KB1(5), SERPINB6(3), SHC1(7), SLC2A4(9), SORBS1(18), SOS1(13), SOS2(17), YWHAE(4), YWHAG(3), YWHAH(3), YWHAQ(1), YWHAZ(1) | 21082232 | 829 | 217 | 605 | 120 | 160 | 197 | 174 | 40 | 214 | 44 | 5.04e-12 | <1.00e-15 | <3.99e-14
5 | SIG_PIP3_SIGNALING_IN_B_LYMPHOCYTES | Genes related to PIP3 signaling in B lymphocytes | AKT1, AKT2, AKT3, BCR, BTK, CD19, CDKN2A, DAPP1, FLOT1, FLOT2, FOXO3A, GAB1, ITPR1, ITPR2, ITPR3, LYN, NR0B2, P101-PI3K, PDK1, PHF11, PIK3CA, PITX2, PLCG2, PPP1R13B, PREX1, PSCD3, PTEN, PTPRC, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KB1, SAG, SYK, TEC, VAV1 | 32 | AKT1(4), AKT2(6), AKT3(11), BCR(6), BTK(12), CD19(4), CDKN2A(2), DAPP1(9), FLOT2(2), GAB1(8), ITPR1(36), ITPR2(35), ITPR3(21), LYN(9), NR0B2(2), PDK1(2), PHF11(5), PIK3CA(172), PITX2(12), PLCG2(29), PPP1R13B(9), PREX1(25), PTEN(227), PTPRC(17), RPS6KA1(1), RPS6KA2(14), RPS6KA3(19), RPS6KB1(5), SAG(10), SYK(4), TEC(8), VAV1(12) | 20541344 | 738 | 212 | 540 | 128 | 147 | 231 | 144 | 38 | 149 | 29 | 5.04e-10 | <1.00e-15 | <3.99e-14
6 | ST_PHOSPHOINOSITIDE_3_KINASE_PATHWAY | The phosphoinositide-3 kinase pathway produces the lipid second messenger PIP3 and regulates cell growth, survival, and movement. | A1BG, AKT1, AKT2, AKT3, BAD, BTK, CDKN2A, CSL4, DAF, DAPP1, FOXO1A, GRB2, GSK3A, GSK3B, IARS, IGFBP1, INPP5D, P14, PDK1, PIK3CA, PPP1R13B, PSCD3, PTEN, RPS6KA1, RPS6KA2, RPS6KA3, RPS6KB1, SFN, SHC1, SOS1, SOS2, TEC, YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ, YWHAZ | 33 | A1BG(3), AKT1(4), AKT2(6), AKT3(11), BAD(2), BTK(12), CDKN2A(2), DAPP1(9), GRB2(3), GSK3A(10), GSK3B(13), IARS(8), IGFBP1(4), INPP5D(9), PDK1(2), PIK3CA(172), PPP1R13B(9), PTEN(227), RPS6KA1(1), RPS6KA2(14), RPS6KA3(19), RPS6KB1(5), SHC1(7), SOS1(13), SOS2(17), TEC(8), YWHAE(4), YWHAG(3), YWHAH(3), YWHAQ(1), YWHAZ(1) | 13352320 | 602 | 211 | 404 | 65 | 112 | 161 | 131 | 37 | 133 | 28 | 1.22e-15 | <1.00e-15 | <3.99e-14
7 | 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 | AKT1(4), APC(56), AXIN1(9), CCND1(15), CD14(2), CTNNB1(80), DVL1(3), FZD1(3), GJA1(5), GNAI1(5), GSK3B(13), IRAK1(4), LBP(3), LEF1(9), LY96(4), MYD88(3), NFKB1(10), PDPK1(3), PIK3CA(172), PIK3R1(100), PPP2CA(6), RELA(6), TIRAP(2), TLR4(17), TOLLIP(1), WNT1(1) | 11218032 | 536 | 210 | 356 | 58 | 77 | 201 | 122 | 6 | 110 | 20 | 9.76e-14 | <1.00e-15 | <3.99e-14
8 | 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(5), AGT(8), AKT1(4), CALM1(2), CALM2(4), CALR(3), CAMK1(2), CAMK1G(5), CAMK4(5), CREBBP(32), CSNK1A1(4), EDN1(4), ELSPBP1(5), F2(8), FKBP1A(1), GATA4(3), GSK3B(13), HAND1(6), HRAS(1), IGF1(5), LIF(3), MAP2K1(2), MAPK1(2), MAPK14(4), MAPK3(3), MAPK8(10), MEF2C(11), MYH2(43), NFATC1(10), NFATC2(13), NFATC3(12), NFATC4(7), NKX2-5(2), NPPA(2), PIK3CA(172), PIK3R1(100), PPP3CA(4), PPP3CB(5), PPP3CC(6), PRKACB(3), PRKACG(9), PRKAR1A(4), PRKAR1B(4), PRKAR2A(4), PRKAR2B(3), RAF1(8), RPS6KB1(5), SYT1(4) | 18646128 | 575 | 207 | 445 | 97 | 126 | 176 | 137 | 5 | 113 | 18 | 3.38e-08 | <1.00e-15 | <3.99e-14
9 | IL2RBPATHWAY | The beta subunit of the IL-2 receptor is required for IL-2 and IL-15 signal recognition and activates JAK kinase on ligand binding. | AKT1, BAD, BCL2, BCL2L1, CBL, CFLAR, CRKL, E2F1, FOS, GRB2, HRAS, IL2RA, IL2RB, IL2RG, IRS1, JAK1, JAK3, MAPK1, MAPK3, MYC, NMI, PIK3CA, PIK3R1, PPIA, PTPN6, RAF1, RPS6KB1, SHC1, SOCS1, SOCS3, SOS1, STAT5A, STAT5B, SYK, TNFRSF6, TNFSF6, ZNFN1A3 | 33 | AKT1(4), BAD(2), BCL2L1(4), CBL(12), CFLAR(6), CRKL(6), E2F1(9), FOS(3), GRB2(3), HRAS(1), IL2RA(4), IL2RB(3), IL2RG(13), IRS1(13), JAK1(20), JAK3(10), MAPK1(2), MAPK3(3), MYC(8), NMI(3), PIK3CA(172), PIK3R1(100), PPIA(1), PTPN6(6), RAF1(8), RPS6KB1(5), SHC1(7), SOS1(13), STAT5A(5), STAT5B(7), SYK(4) | 13344136 | 457 | 203 | 334 | 55 | 84 | 140 | 122 | 5 | 91 | 15 | 1.67e-10 | <1.00e-15 | <3.99e-14
10 | AKTPATHWAY | Second messenger PIP3 promotes cell survival by activating the anti-apoptotic kinase AKT. | AKT1, BAD, CASP9, CHUK, FOXO1A, FOXO3A, GH1, GHR, HSPCA, MLLT7, NFKB1, NFKBIA, PDPK1, PIK3CA, PIK3R1, PPP2CA, RELA, TNFSF6, YWHAH | 14 | AKT1(4), BAD(2), CASP9(3), CHUK(8), GH1(3), GHR(8), NFKB1(10), NFKBIA(3), PDPK1(3), PIK3CA(172), PIK3R1(100), PPP2CA(6), RELA(6), YWHAH(3) | 5298520 | 331 | 199 | 212 | 19 | 49 | 93 | 92 | 4 | 78 | 15 | 3.56e-13 | <1.00e-15 | <3.99e-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 | HSA00627_1,4_DICHLOROBENZENE_DEGRADATION | Genes involved in 1,4-dichlorobenzene degradation | CMBL | 1 | CMBL(3) | 187984 | 3 | 3 | 3 | 1 | 0 | 1 | 0 | 1 | 1 | 0 | 0.81 | 0.18 | 1
2 | 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) | 635128 | 10 | 10 | 9 | 0 | 2 | 5 | 2 | 0 | 1 | 0 | 0.057 | 0.32 | 1
3 | HSA00472_D_ARGININE_AND_D_ORNITHINE_METABOLISM | Genes involved in D-arginine and D-ornithine metabolism | DAO | 1 | DAO(8) | 268832 | 8 | 6 | 8 | 1 | 2 | 4 | 2 | 0 | 0 | 0 | 0.3 | 0.33 | 1
4 | TCRMOLECULE | T Cell Receptor and CD3 Complex | CD3D, CD3E, CD3G, CD3Z, TRA@, TRB@ | 3 | CD3D(6), CD3E(2), CD3G(3) | 437720 | 11 | 7 | 11 | 1 | 1 | 7 | 0 | 0 | 3 | 0 | 0.18 | 0.41 | 1
5 | 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) | 1950272 | 39 | 23 | 39 | 7 | 10 | 15 | 9 | 0 | 5 | 0 | 0.057 | 0.42 | 1
6 | 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) | 2324752 | 40 | 27 | 40 | 9 | 6 | 20 | 4 | 0 | 10 | 0 | 0.18 | 0.42 | 1
7 | P27PATHWAY | p27 blocks the G1/S transition by inhibiting the checkpoint kinase cdk2/cyclin E and is inhibited by cdk2-mediated ubiquitination. | CCNE1, CDK2, CDKN1B, CKS1B, CUL1, E2F1, NEDD8, RB1, RBX1, SKP1A, SKP2, TFDP1, UBE2M | 12 | CCNE1(6), CDK2(2), CDKN1B(7), CKS1B(1), CUL1(13), E2F1(9), RB1(26), RBX1(1), SKP2(7), TFDP1(13) | 3255992 | 85 | 39 | 83 | 17 | 27 | 25 | 17 | 0 | 13 | 3 | 0.027 | 0.43 | 1
8 | HSA00643_STYRENE_DEGRADATION | Genes involved in styrene degradation | FAH, GSTZ1, HGD | 3 | FAH(6), GSTZ1(5), HGD(4) | 842456 | 15 | 12 | 15 | 2 | 5 | 4 | 4 | 0 | 2 | 0 | 0.11 | 0.48 | 1
9 | HSA00031_INOSITOL_METABOLISM | Genes involved in inositol metabolism | ALDH6A1, TPI1 | 2 | ALDH6A1(6), TPI1(2) | 594208 | 8 | 7 | 8 | 1 | 0 | 3 | 1 | 0 | 4 | 0 | 0.28 | 0.56 | 1
10 | SA_BONE_MORPHOGENETIC | Bone morphogenetic protein binds to its receptor to induce ectopic bone formation and promote development of the viscera. | BMP1, BMPR1A, BMPR1B, BMPR2, MADH1, MADH4, MADH6 | 4 | BMP1(19), BMPR1A(5), BMPR1B(6), BMPR2(12) | 2288296 | 42 | 24 | 42 | 5 | 13 | 15 | 7 | 2 | 5 | 0 | 0.026 | 0.58 | 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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