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.

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