Mutation Analysis (MutSig v2.0)
Glioblastoma Multiforme (Primary solid tumor)
22 February 2013  |  analyses__2013_02_22
Maintainer Information
Citation Information
doi:10.7908/C14X5600
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/C14X5600
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: GBM-TP

  • Number of patients in set: 291

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:GBM-TP.final_analysis_set.maf

  • Significantly mutated genes (q ≤ 0.1): 85

  • Mutations seen in COSMIC: 495

  • Significantly mutated genes in COSMIC territory: 80

  • Genes with clustered mutations (≤ 3 aa apart): 277

  • Significantly mutated genesets: 119

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

Mutation Preprocessing

  • Read 291 MAFs of type "Broad"

  • Total number of mutations in input MAFs: 21540

  • After removing 126 blacklisted mutations: 21414

Mutation Filtering

  • Number of mutations before filtering: 21414

Results
Breakdown of Mutations by Type

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

type count
Frame_Shift_Del 547
Frame_Shift_Ins 209
In_Frame_Del 209
In_Frame_Ins 27
Missense_Mutation 13817
Nonsense_Mutation 831
Nonstop_Mutation 11
Silent 5348
Splice_Site 355
Translation_Start_Site 60
Total 21414
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 5667 484801968 0.000012 12 6.3 2.1
*Cp(A/C/T)->T 2473 3955187453 6.3e-07 0.63 0.34 1.7
A->G 1716 4258795879 4e-07 0.4 0.22 2.3
transver 4020 8698785300 4.6e-07 0.46 0.25 5
indel+null 2190 8698785300 2.5e-07 0.25 0.14 NaN
double_null 0 8698785300 0 0 0 NaN
Total 16066 8698785300 1.8e-06 1.8 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: GBM-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: A->G

  • n4 = number of nonsilent mutations of type: transver

  • 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: 85. 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 PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (alpha) 687164 34 33 28 0 0 3 4 7 20 0 7.55e-15 0.0059 0.28 4.8e-06 0.000 0.000
2 TP53 tumor protein p53 368172 100 83 61 1 31 15 11 24 19 0 <1.00e-15 1.3e-11 0 0 <1.00e-15 <3.63e-12
3 EGFR epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian) 1163406 95 77 45 7 10 45 2 33 5 0 1.33e-15 4.2e-09 0 0 <1.00e-15 <3.63e-12
4 IDH1 isocitrate dehydrogenase 1 (NADP+), soluble 371447 15 15 2 0 13 0 0 2 0 0 3.55e-15 0.0065 0.84 0 <1.00e-15 <3.63e-12
5 BRAF v-raf murine sarcoma viral oncogene homolog B1 648921 6 6 2 1 0 1 0 5 0 0 0.000350 0.62 0.085 0 <1.00e-15 <3.63e-12
6 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 347800 93 90 75 0 5 21 10 14 43 0 <1.00e-15 1.1e-09 0.6 0.03 <1.22e-15 <3.69e-12
7 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 950995 35 32 28 0 5 9 8 6 7 0 1.44e-15 0.00015 0.23 0.027 1.55e-15 4.03e-12
8 RB1 retinoblastoma 1 (including osteosarcoma) 773460 24 24 22 1 0 0 0 1 23 0 3.22e-15 0.097 0.062 0.065 7.77e-15 1.76e-11
9 NF1 neurofibromin 1 (neurofibromatosis, von Recklinghausen disease, Watson disease) 2527351 34 32 33 1 0 2 2 2 28 0 6.55e-15 0.0041 0.95 0.5 1.13e-13 2.28e-10
10 SPTA1 spectrin, alpha, erythrocytic 1 (elliptocytosis 2) 2171581 29 27 27 1 11 4 1 9 4 0 7.11e-15 0.01 0.5 0.72 1.74e-13 3.15e-10
11 KRTAP4-11 keratin associated protein 4-11 152984 9 9 5 0 1 4 0 4 0 0 8.03e-12 0.049 1 0.24 5.33e-11 8.79e-08
12 GABRA6 gamma-aminobutyric acid (GABA) A receptor, alpha 6 406622 11 11 10 1 4 2 1 4 0 0 3.47e-11 0.11 0.38 0.76 6.65e-10 1.01e-06
13 KEL Kell blood group, metallo-endopeptidase 657936 15 15 12 2 8 0 1 3 3 0 2.89e-10 0.19 0.93 0.68 4.59e-09 6.40e-06
14 RPL5 ribosomal protein L5 269214 8 8 8 0 0 1 1 0 6 0 1.15e-09 0.28 0.24 0.43 1.12e-08 1.44e-05
15 PRB2 proline-rich protein BstNI subfamily 2 367479 6 6 2 0 0 0 0 0 6 0 1.31e-06 1 0.63 0.0019 5.08e-08 5.76e-05
16 CDH18 cadherin 18, type 2 702163 11 11 10 0 3 3 0 4 1 0 1.74e-08 0.048 0.76 0.14 5.08e-08 5.76e-05
17 SEMA3C sema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3C 673506 11 11 11 1 3 0 2 5 1 0 1.14e-08 0.22 0.57 0.65 1.46e-07 0.000156
18 TPTE2 transmembrane phosphoinositide 3-phosphatase and tensin homolog 2 477884 8 8 6 0 2 1 0 2 3 0 4.12e-07 0.1 0.031 0.02 1.64e-07 0.000165
19 ZNF844 zinc finger protein 844 448463 6 6 3 1 0 0 2 4 0 0 4.38e-05 0.5 1 0.00037 3.10e-07 0.000296
20 OR8K3 olfactory receptor, family 8, subfamily K, member 3 273211 7 7 7 1 2 2 0 2 1 0 2.97e-08 0.32 0.95 0.7 3.91e-07 0.000355
21 OR5AR1 olfactory receptor, family 5, subfamily AR, member 1 271597 7 7 7 0 3 0 2 2 0 0 1.03e-07 0.18 0.098 0.24 4.51e-07 0.000389
22 STAG2 stromal antigen 2 1141918 12 12 12 0 0 0 0 2 10 0 6.41e-08 0.19 0.63 0.57 6.58e-07 0.000542
23 SEMG1 semenogelin I 406527 8 8 7 0 5 0 2 0 1 0 9.15e-08 0.11 0.52 0.5 8.22e-07 0.000648
24 CDC27 cell division cycle 27 homolog (S. cerevisiae) 736005 7 6 3 0 0 0 1 0 6 0 0.000241 0.61 0.042 0.00023 9.95e-07 0.000751
25 PDGFRA platelet-derived growth factor receptor, alpha polypeptide 977162 13 11 12 1 0 5 2 4 2 0 7.69e-07 0.096 0.29 0.17 2.19e-06 0.00159
26 IFNA10 interferon, alpha 10 163489 4 2 2 1 0 2 2 0 0 0 0.00516 0.46 0.68 0.000043 3.65e-06 0.00255
27 SULT1B1 sulfotransferase family, cytosolic, 1B, member 1 265051 7 6 7 1 0 2 1 3 1 0 1.19e-06 0.36 0.89 0.26 4.98e-06 0.00334
28 ADAM29 ADAM metallopeptidase domain 29 717863 9 9 8 1 6 0 0 2 1 0 5.12e-07 0.34 0.64 0.65 5.28e-06 0.00342
29 HEATR7B2 HEAT repeat family member 7B2 1295264 12 12 12 2 3 1 0 6 2 0 2.35e-05 0.31 0.69 0.018 6.59e-06 0.00412
30 COL1A2 collagen, type I, alpha 2 1195564 12 12 12 1 3 3 0 6 0 0 1.81e-06 0.16 0.21 0.29 8.14e-06 0.00492
31 ABCC9 ATP-binding cassette, sub-family C (CFTR/MRP), member 9 1435985 14 11 14 1 4 0 3 5 2 0 9.65e-06 0.1 0.42 0.062 9.18e-06 0.00537
32 NLRP5 NLR family, pyrin domain containing 5 989666 12 12 11 2 9 0 1 2 0 0 4.51e-06 0.11 0.064 0.19 1.27e-05 0.00722
33 LZTR1 leucine-zipper-like transcription regulator 1 666005 10 10 10 0 4 0 1 4 1 0 4.87e-06 0.08 0.21 0.26 1.81e-05 0.00993
34 CALCR calcitonin receptor 436734 8 8 8 0 6 1 1 0 0 0 1.28e-06 0.051 0.82 1 1.86e-05 0.00993
35 QKI quaking homolog, KH domain RNA binding (mouse) 337207 5 5 5 0 0 0 0 2 3 0 4.06e-05 0.69 0.0058 0.034 2.02e-05 0.0104
PIK3R1

Figure S1.  This figure depicts the distribution of mutations and mutation types across the PIK3R1 significant gene.

TP53

Figure S2.  This figure depicts the distribution of mutations and mutation types across the TP53 significant gene.

EGFR

Figure S3.  This figure depicts the distribution of mutations and mutation types across the EGFR significant gene.

IDH1

Figure S4.  This figure depicts the distribution of mutations and mutation types across the IDH1 significant gene.

BRAF

Figure S5.  This figure depicts the distribution of mutations and mutation types across the BRAF significant gene.

PTEN

Figure S6.  This figure depicts the distribution of mutations and mutation types across the PTEN significant gene.

PIK3CA

Figure S7.  This figure depicts the distribution of mutations and mutation types across the PIK3CA significant gene.

RB1

Figure S8.  This figure depicts the distribution of mutations and mutation types across the RB1 significant gene.

NF1

Figure S9.  This figure depicts the distribution of mutations and mutation types across the NF1 significant gene.

SPTA1

Figure S10.  This figure depicts the distribution of mutations and mutation types across the SPTA1 significant gene.

KRTAP4-11

Figure S11.  This figure depicts the distribution of mutations and mutation types across the KRTAP4-11 significant gene.

GABRA6

Figure S12.  This figure depicts the distribution of mutations and mutation types across the GABRA6 significant gene.

KEL

Figure S13.  This figure depicts the distribution of mutations and mutation types across the KEL significant gene.

RPL5

Figure S14.  This figure depicts the distribution of mutations and mutation types across the RPL5 significant gene.

CDH18

Figure S15.  This figure depicts the distribution of mutations and mutation types across the CDH18 significant gene.

SEMA3C

Figure S16.  This figure depicts the distribution of mutations and mutation types across the SEMA3C significant gene.

TPTE2

Figure S17.  This figure depicts the distribution of mutations and mutation types across the TPTE2 significant gene.

ZNF844

Figure S18.  This figure depicts the distribution of mutations and mutation types across the ZNF844 significant gene.

OR8K3

Figure S19.  This figure depicts the distribution of mutations and mutation types across the OR8K3 significant gene.

OR5AR1

Figure S20.  This figure depicts the distribution of mutations and mutation types across the OR5AR1 significant gene.

STAG2

Figure S21.  This figure depicts the distribution of mutations and mutation types across the STAG2 significant gene.

SEMG1

Figure S22.  This figure depicts the distribution of mutations and mutation types across the SEMG1 significant gene.

CDC27

Figure S23.  This figure depicts the distribution of mutations and mutation types across the CDC27 significant gene.

PDGFRA

Figure S24.  This figure depicts the distribution of mutations and mutation types across the PDGFRA significant gene.

IFNA10

Figure S25.  This figure depicts the distribution of mutations and mutation types across the IFNA10 significant gene.

SULT1B1

Figure S26.  This figure depicts the distribution of mutations and mutation types across the SULT1B1 significant gene.

ADAM29

Figure S27.  This figure depicts the distribution of mutations and mutation types across the ADAM29 significant gene.

HEATR7B2

Figure S28.  This figure depicts the distribution of mutations and mutation types across the HEATR7B2 significant gene.

COL1A2

Figure S29.  This figure depicts the distribution of mutations and mutation types across the COL1A2 significant gene.

ABCC9

Figure S30.  This figure depicts the distribution of mutations and mutation types across the ABCC9 significant gene.

NLRP5

Figure S31.  This figure depicts the distribution of mutations and mutation types across the NLRP5 significant gene.

LZTR1

Figure S32.  This figure depicts the distribution of mutations and mutation types across the LZTR1 significant gene.

CALCR

Figure S33.  This figure depicts the distribution of mutations and mutation types across the CALCR significant gene.

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: 80. Number of genes displayed: 10

rank gene description n cos n_cos N_cos cos_ev p q
1 IDH1 isocitrate dehydrogenase 1 (NADP+), soluble 15 5 15 1455 22380 0 0
2 PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (alpha) 34 33 14 9603 32 0 0
3 TP53 tumor protein p53 100 356 96 103596 27718 0 0
4 EGFR epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian) 95 293 72 85263 1161 0 0
5 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 35 220 27 64020 6345 0 0
6 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 93 767 91 223197 3249 0 0
7 RB1 retinoblastoma 1 (including osteosarcoma) 24 267 15 77697 41 0 0
8 NF1 neurofibromin 1 (neurofibromatosis, von Recklinghausen disease, Watson disease) 34 285 14 82935 27 0 0
9 PTPN11 protein tyrosine phosphatase, non-receptor type 11 (Noonan syndrome 1) 5 32 5 9312 20 1.2e-11 6.1e-09
10 BRAF v-raf murine sarcoma viral oncogene homolog B1 6 89 6 25899 71896 1.6e-11 7.1e-09

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
2138 EGFR epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian) 95 0 317 397 432 317 397 432
3198 IDH1 isocitrate dehydrogenase 1 (NADP+), soluble 15 0 105 105 105 105 105 105
7300 TP53 tumor protein p53 100 0 102 244 573 102 244 573
5744 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 93 0 37 98 233 37 98 233
5387 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 35 0 16 40 54 16 40 54
5390 PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (alpha) 34 0 11 26 34 11 26 34
721 BRAF v-raf murine sarcoma viral oncogene homolog B1 6 0 10 10 15 10 10 15
3741 KRTAP4-11 keratin associated protein 4-11 9 0 6 9 13 6 9 13
4475 NBPF10 neuroblastoma breakpoint family, member 10 11 0 6 6 6 6 6 6
5892 RB1 retinoblastoma 1 (including osteosarcoma) 24 0 4 5 11 4 5 11

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: 119. 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 METPATHWAY The hepatocyte growth factor receptor c-Met stimulates proliferation and alters cell motility and adhesion on binding the ligand HGF. ACTA1, CRK, CRKL, DOCK1, ELK1, FOS, GAB1, GRB2, GRF2, HGF, HRAS, ITGA1, ITGB1, JUN, MAP2K1, MAP2K2, MAP4K1, MAPK1, MAPK3, MAPK8, MET, PAK1, PIK3CA, PIK3R1, PTEN, PTK2, PTK2B, PTPN11, PXN, RAF1, RAP1A, RAP1B, RASA1, SOS1, SRC, STAT3 35 CRKL(1), DOCK1(2), ELK1(2), FOS(1), HGF(1), ITGA1(2), ITGB1(1), MAP2K1(1), MAP4K1(2), MAPK1(2), MAPK3(1), MAPK8(1), MET(3), PAK1(1), PIK3CA(35), PIK3R1(34), PTEN(93), PTK2B(3), PTPN11(5), PXN(1), RAF1(1), SOS1(3), SRC(2), STAT3(1) 19365179 199 155 168 5 21 39 26 40 73 0 <1.00e-15 <1.00e-15 <5.70e-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(1), EIF4A1(1), EIF4B(1), EIF4G1(1), EIF4G3(1), PIK3CA(35), PIK3R1(34), PTEN(93), TSC2(4) 12107623 171 144 140 2 12 35 22 31 71 0 <1.00e-15 <1.00e-15 <5.70e-14
3 PTENPATHWAY PTEN suppresses AKT-induced cell proliferation and antagonizes the action of PI3K. AKT1, BCAR1, CDKN1B, FOXO3A, GRB2, ILK, ITGB1, MAPK1, MAPK3, PDK2, PDPK1, PIK3CA, PIK3R1, PTEN, PTK2, SHC1, SOS1, TNFSF6 16 AKT1(1), CDKN1B(1), ITGB1(1), MAPK1(2), MAPK3(1), PIK3CA(35), PIK3R1(34), PTEN(93), SOS1(3) 8464209 171 142 140 0 11 35 25 30 70 0 <1.00e-15 <1.00e-15 <5.70e-14
4 HCMVPATHWAY Cytomegalovirus activates MAP kinase pathways in the host cell, inducing transcription of viral genes. AKT1, CREB1, MAP2K1, MAP2K2, MAP2K3, MAP2K6, MAP3K1, MAPK1, MAPK14, MAPK3, NFKB1, PIK3CA, PIK3R1, RB1, RELA, SP1 16 AKT1(1), CREB1(1), MAP2K1(1), MAP2K3(3), MAP3K1(6), MAPK1(2), MAPK3(1), NFKB1(1), PIK3CA(35), PIK3R1(34), RB1(24), SP1(1) 8507902 110 94 93 4 10 18 14 15 53 0 5.18e-08 <1.00e-15 <5.70e-14
5 CHEMICALPATHWAY DNA damage promotes Bid cleavage, which stimulates mitochondrial cytochrome c release and consequent caspase activation, resulting in apoptosis. ADPRT, AKT1, APAF1, ATM, BAD, BAX, BCL2, BCL2L1, BID, CASP3, CASP6, CASP7, CASP9, CYCS, EIF2S1, PRKCA, PRKCB1, PTK2, PXN, STAT1, TLN1, TP53 20 AKT1(1), ATM(4), BCL2(2), CASP9(1), PRKCA(1), PXN(1), STAT1(2), TP53(100) 12014139 112 93 73 2 32 16 13 27 24 0 5.17e-12 <1.00e-15 <5.70e-14
6 RNAPATHWAY dsRNA-activated protein kinase phosphorylates elF2a, which generally inhibits translation, and activates NF-kB to provoke inflammation. CHUK, DNAJC3, EIF2S1, EIF2S2, MAP3K14, NFKB1, NFKBIA, PRKR, RELA, TP53 9 CHUK(1), EIF2S2(1), NFKB1(1), NFKBIA(1), TP53(100) 4335333 104 86 65 2 32 15 12 25 20 0 3.24e-11 <1.00e-15 <5.70e-14
7 CTLA4PATHWAY T cell activation requires interaction with an antigen-MHC-I complex on an antigen-presenting cell (APC), as well as CD28 interaction with the APC's CD80 or 86. CD28, CD3D, CD3E, CD3G, CD3Z, CD80, CD86, CTLA4, GRB2, HLA-DRA, HLA-DRB1, ICOS, ICOSL, IL2, ITK, LCK, PIK3CA, PIK3R1, PTPN11, TRA@, TRB@ 17 CD28(1), CD3E(2), CD3G(1), CD86(2), HLA-DRA(1), PIK3CA(35), PIK3R1(34), PTPN11(5) 5564653 81 72 68 3 9 13 13 18 28 0 7.95e-06 <1.00e-15 <5.70e-14
8 LONGEVITYPATHWAY Caloric restriction in animals often increases lifespan, which may occur via decreased IGF receptor expression and consequent expression of stress-resistance proteins. AKT1, CAT, FOXO3A, GH1, GHR, HRAS, IGF1, IGF1R, PIK3CA, PIK3R1, SHC1, SOD1, SOD2, SOD3 13 AKT1(1), GH1(1), IGF1(2), IGF1R(3), PIK3CA(35), PIK3R1(34) 5803893 76 69 63 3 5 14 13 16 28 0 1.25e-05 <1.00e-15 <5.70e-14
9 SA_G1_AND_S_PHASES Cdk2, 4, and 6 bind cyclin D in G1, while cdk2/cyclin E promotes the G1/S transition. ARF1, ARF3, CCND1, CDK2, CDK4, CDKN1A, CDKN1B, CDKN2A, CFL1, E2F1, E2F2, MDM2, NXT1, PRB1, TP53 15 CDKN1A(1), CDKN1B(1), CDKN2A(2), MDM2(2), PRB1(1), TP53(100) 3638352 107 87 68 2 32 16 12 25 22 0 1.40e-12 1.11e-15 5.70e-14
10 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 49 AKT1(1), BRD4(1), CBL(1), CDKN2A(2), FLOT1(1), GSK3B(1), INPPL1(3), IRS1(4), IRS4(3), LNPEP(2), MAPK1(2), MAPK3(1), PARD3(1), PIK3CA(35), PIK3R1(34), PPYR1(1), PTEN(93), RAF1(1), RPS6KA1(1), RPS6KA2(2), RPS6KA3(1), SFN(1), SORBS1(2), SOS1(3), YWHAE(2), YWHAH(1) 25933575 200 159 169 10 15 39 28 38 80 0 1.11e-12 1.22e-15 5.70e-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 HSA00472_D_ARGININE_AND_D_ORNITHINE_METABOLISM Genes involved in D-arginine and D-ornithine metabolism DAO 1 DAO(4) 314850 4 4 4 0 3 1 0 0 0 0 0.22 0.0022 1
2 ACE_INHIBITOR_PATHWAY_PHARMGKB ACE, AGT, AGTR1, AGTR2, BDKRB2, KNG1, NOS3, REN 8 ACE(5), AGT(1), AGTR1(1), AGTR2(1), KNG1(2), NOS3(4), REN(5) 4406003 19 19 18 2 11 2 0 2 4 0 0.029 0.0077 1
3 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(2), IFNG(2), IL12B(2) 1305817 6 6 6 1 2 1 1 0 2 0 0.34 0.0091 1
4 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(1), CD3E(2), CD3G(1), CD4(1), CD58(1), CD8A(1), IL3(1), IL6(1), KITLG(1) 2719987 10 10 10 1 3 1 1 3 2 0 0.15 0.0092 1
5 FXRPATHWAY The nuclear receptor transcription factors FXR and LXR are activated by cholesterol metabolites and regulate cholesterol homeostasis. FABP6, LDLR, NR0B2, NR1H3, NR1H4, RXRA 6 FABP6(1), LDLR(3), NR0B2(1), NR1H3(1), NR1H4(3), RXRA(3) 2385306 12 12 12 2 5 2 0 4 1 0 0.18 0.011 1
6 IFNGPATHWAY IFN gamma signaling pathway IFNG, IFNGR1, IFNGR2, JAK1, JAK2, STAT1 6 IFNG(2), IFNGR1(1), IFNGR2(3), JAK1(2), JAK2(2), STAT1(2) 3570580 12 12 12 0 0 0 3 6 3 0 0.057 0.012 1
7 NUCLEOTIDE_SUGARS_METABOLISM GALE, GALT, TGDS, UGDH, UXS1 5 GALE(2), GALT(1), TGDS(1), UGDH(1), UXS1(2) 1713298 7 7 7 0 1 1 1 2 2 0 0.14 0.016 1
8 TCRMOLECULE T Cell Receptor and CD3 Complex CD3D, CD3E, CD3G, CD3Z, TRA@, TRB@ 3 CD3E(2), CD3G(1) 497037 3 3 3 0 0 0 1 1 1 0 0.42 0.017 1
9 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(1), CD28(1), CD3E(2), CD3G(1), CD4(1) 1402861 6 6 6 1 3 0 1 1 1 0 0.36 0.018 1
10 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 8 CCR3(1), CSF2(2), HLA-DRA(1), IL3(1) 1326217 5 5 5 0 2 1 1 0 1 0 0.2 0.036 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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