Mutation Analysis (MutSig v2.0)
Glioblastoma Multiforme (Primary solid tumor)
21 April 2013  |  analyses__2013_04_21
Maintainer Information
Citation Information
doi:10.7908/C1TH8JNV
Maintained by Dan DiCara (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Glioblastoma Multiforme (Primary solid tumor cohort) - 21 April 2013: Mutation Analysis (MutSig v2.0). Broad Institute of MIT and Harvard. doi:10.7908/C1TH8JNV
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: 284

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): 81

  • Mutations seen in COSMIC: 466

  • Significantly mutated genes in COSMIC territory: 74

  • Genes with clustered mutations (≤ 3 aa apart): 261

  • Significantly mutated genesets: 119

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

Mutation Preprocessing

  • Read 284 MAFs of type "Broad"

  • Total number of mutations in input MAFs: 21603

  • After removing 304 blacklisted mutations: 21299

Mutation Filtering

  • Number of mutations before filtering: 21299

  • After removing 413 mutations outside gene set: 20886

  • After removing 12 mutations outside category set: 20874

Results
Breakdown of Mutations by Type

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

type count
Frame_Shift_Del 536
Frame_Shift_Ins 204
In_Frame_Del 204
In_Frame_Ins 27
Missense_Mutation 13461
Nonsense_Mutation 809
Nonstop_Mutation 11
Silent 5229
Splice_Site 339
Translation_Start_Site 54
Total 20874
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 5501 473068624 0.000012 12 6.3 2.1
*Cp(A/C/T)->T 2412 3859508772 6.2e-07 0.62 0.34 1.7
A->G 1682 4155773265 4e-07 0.4 0.22 2.3
transver 3919 8488350661 4.6e-07 0.46 0.25 5
indel+null 2119 8488350661 2.5e-07 0.25 0.14 NaN
double_null 12 8488350661 1.4e-09 0.0014 0.00077 NaN
Total 15645 8488350661 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: 81. 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) 670609 33 32 27 0 0 3 4 7 19 0 7.7e-15 0.0059 0.12 0.000012 0.000 0.000
2 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 339074 90 87 73 0 5 20 10 13 42 0 1.1e-15 1.9e-09 0.49 0.019 8.88e-16 3.02e-12
3 TP53 tumor protein p53 359363 96 79 59 1 29 15 11 23 18 0 1.1e-15 2.8e-11 0 0 <1.00e-15 <3.02e-12
4 EGFR epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian) 1135441 92 74 44 7 10 44 2 32 4 0 3.4e-15 1.1e-08 0 0 <1.00e-15 <3.02e-12
5 IDH1 isocitrate dehydrogenase 1 (NADP+), soluble 362508 14 14 2 0 13 0 0 1 0 0 1.3e-14 0.0076 0.86 0 <1.00e-15 <3.02e-12
6 BRAF v-raf murine sarcoma viral oncogene homolog B1 633304 6 6 2 1 0 1 0 5 0 0 0.00031 0.62 0.085 0 <1.00e-15 <3.02e-12
7 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 927986 33 30 28 0 5 8 7 6 7 0 8.1e-15 0.00033 0.26 0.03 9.10e-15 2.36e-11
8 RB1 retinoblastoma 1 (including osteosarcoma) 754622 24 24 22 1 0 0 0 1 22 1 6.7e-15 0.097 0.062 0.061 1.49e-14 3.37e-11
9 NF1 neurofibromin 1 (neurofibromatosis, von Recklinghausen disease, Watson disease) 2466191 30 29 30 1 0 2 1 1 21 5 4.8e-15 0.011 0.97 0.35 5.78e-14 1.17e-10
10 SPTA1 spectrin, alpha, erythrocytic 1 (elliptocytosis 2) 2119313 28 26 27 0 11 4 1 9 3 0 7.6e-15 0.0016 0.49 0.74 1.89e-13 3.43e-10
11 KRTAP4-11 keratin associated protein 4-11 149093 9 9 5 0 1 4 0 4 0 0 6.3e-12 0.049 1 0.24 4.31e-11 7.11e-08
12 GABRA6 gamma-aminobutyric acid (GABA) A receptor, alpha 6 396836 11 11 10 1 4 2 1 4 0 0 2.7e-11 0.11 0.38 0.76 5.19e-10 7.84e-07
13 KEL Kell blood group, metallo-endopeptidase 642032 15 15 12 2 8 0 1 3 3 0 2.1e-10 0.19 0.93 0.7 3.51e-09 4.89e-06
14 CDH18 cadherin 18, type 2 685244 11 11 10 0 3 3 0 4 1 0 1.3e-08 0.048 0.76 0.14 3.97e-08 5.14e-05
15 PRB2 proline-rich protein BstNI subfamily 2 358638 6 6 2 0 0 0 0 0 6 0 1.1e-06 1 0.63 0.0019 4.27e-08 5.16e-05
16 RPL5 ribosomal protein L5 262732 7 7 7 0 0 1 1 0 5 0 2e-08 0.28 0.081 0.19 7.68e-08 8.71e-05
17 SEMA3C sema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3C 657239 11 11 11 1 3 0 2 5 1 0 8.8e-09 0.22 0.57 0.65 1.14e-07 0.000122
18 TPTE2 transmembrane phosphoinositide 3-phosphatase and tensin homolog 2 466341 8 8 6 0 2 1 0 2 3 0 3.4e-07 0.1 0.031 0.02 1.38e-07 0.000139
19 ZNF844 zinc finger protein 844 436641 6 6 3 1 0 0 2 4 0 0 0.000038 0.5 1 0.00041 2.92e-07 0.000279
20 OR8K3 olfactory receptor, family 8, subfamily K, member 3 266624 7 7 7 1 2 2 0 2 1 0 2.6e-08 0.32 0.95 0.7 3.39e-07 0.000307
21 OR5AR1 olfactory receptor, family 5, subfamily AR, member 1 265052 7 7 7 0 3 0 2 2 0 0 8.7e-08 0.18 0.098 0.24 3.84e-07 0.000331
22 STAG2 stromal antigen 2 1114350 12 12 12 0 0 0 0 2 10 0 4.9e-08 0.19 0.63 0.57 5.11e-07 0.000421
23 SEMG1 semenogelin I 396748 8 8 7 0 5 0 2 0 1 0 7.6e-08 0.11 0.52 0.5 6.91e-07 0.000544
24 CDC27 cell division cycle 27 homolog (S. cerevisiae) 718119 7 6 3 0 0 0 1 0 6 0 0.00021 0.61 0.042 0.00027 1.01e-06 0.000760
25 PDGFRA platelet-derived growth factor receptor, alpha polypeptide 953656 13 11 12 1 0 5 2 4 2 0 6e-07 0.096 0.29 0.17 1.73e-06 0.00125
26 SULT1B1 sulfotransferase family, cytosolic, 1B, member 1 258618 7 6 7 1 0 2 1 3 1 0 1e-06 0.36 0.89 0.26 4.36e-06 0.00293
27 ADAM29 ADAM metallopeptidase domain 29 700594 9 9 8 1 6 0 0 2 1 0 4.2e-07 0.34 0.64 0.65 4.36e-06 0.00293
28 ABCC9 ATP-binding cassette, sub-family C (CFTR/MRP), member 9 1401377 14 11 14 1 4 0 3 5 2 0 7.6e-06 0.1 0.42 0.062 7.37e-06 0.00477
29 NLRP5 NLR family, pyrin domain containing 5 965717 12 12 11 2 9 0 1 2 0 0 3.6e-06 0.11 0.064 0.2 1.09e-05 0.00681
30 LZTR1 leucine-zipper-like transcription regulator 1 650104 10 10 10 0 4 0 1 4 1 0 3.9e-06 0.08 0.21 0.21 1.23e-05 0.00742
31 CALCR calcitonin receptor 426150 8 8 8 0 6 1 1 0 0 0 1e-06 0.051 0.82 1 1.56e-05 0.00911
32 QKI quaking homolog, KH domain RNA binding (mouse) 329073 5 5 5 0 0 0 0 2 3 0 0.000036 0.69 0.0058 0.034 1.78e-05 0.0101
33 ZPBP zona pellucida binding protein 283221 5 5 4 0 3 0 1 0 1 0 0.000082 0.28 0.42 0.02 2.29e-05 0.0126
34 PSPH phosphoserine phosphatase 198225 5 5 3 0 0 3 0 1 1 0 1e-05 0.26 0.38 0.17 2.50e-05 0.0133
35 UGT2A3 UDP glucuronosyltransferase 2 family, polypeptide A3 452509 6 6 6 0 1 0 2 2 1 0 0.000035 0.15 0.018 0.052 2.57e-05 0.0133
PIK3R1

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

PTEN

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

TP53

Figure S3.  This figure depicts the distribution of mutations and mutation types across the TP53 significant gene.

EGFR

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

IDH1

Figure S5.  This figure depicts the distribution of mutations and mutation types across the IDH1 significant gene.

BRAF

Figure S6.  This figure depicts the distribution of mutations and mutation types across the BRAF 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.

CDH18

Figure S14.  This figure depicts the distribution of mutations and mutation types across the CDH18 significant gene.

RPL5

Figure S15.  This figure depicts the distribution of mutations and mutation types across the RPL5 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.

SULT1B1

Figure S25.  This figure depicts the distribution of mutations and mutation types across the SULT1B1 significant gene.

ADAM29

Figure S26.  This figure depicts the distribution of mutations and mutation types across the ADAM29 significant gene.

ABCC9

Figure S27.  This figure depicts the distribution of mutations and mutation types across the ABCC9 significant gene.

NLRP5

Figure S28.  This figure depicts the distribution of mutations and mutation types across the NLRP5 significant gene.

LZTR1

Figure S29.  This figure depicts the distribution of mutations and mutation types across the LZTR1 significant gene.

CALCR

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

QKI

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

ZPBP

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

PSPH

Figure S33.  This figure depicts the distribution of mutations and mutation types across the PSPH 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: 74. Number of genes displayed: 10

rank gene description n cos n_cos N_cos cos_ev p q
1 TP53 tumor protein p53 96 356 92 101104 26305 0 0
2 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 90 767 88 217828 3057 0 0
3 IDH1 isocitrate dehydrogenase 1 (NADP+), soluble 14 5 14 1420 20888 1.4e-14 2.2e-11
4 PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (alpha) 33 33 13 9372 25 9.3e-14 1e-10
5 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 33 220 25 62480 5654 5.6e-13 4.1e-10
6 RB1 retinoblastoma 1 (including osteosarcoma) 24 267 15 75828 41 6.6e-13 4.1e-10
7 NF1 neurofibromin 1 (neurofibromatosis, von Recklinghausen disease, Watson disease) 30 285 11 80940 23 7e-13 4.1e-10
8 EGFR epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian) 92 293 70 83212 1144 7.2e-13 4.1e-10
9 BRAF v-raf murine sarcoma viral oncogene homolog B1 6 89 6 25276 71896 1.4e-11 7e-09
10 ADAM29 ADAM metallopeptidase domain 29 9 5 3 1420 3 3e-09 1.3e-06

Note:

n - number of (nonsilent) mutations in this gene across the individual set.

cos = number of unique mutated sites in this gene in COSMIC

n_cos = overlap between n and cos.

N_cos = number of individuals times cos.

cos_ev = total evidence: number of reports in COSMIC for mutations seen in this gene.

p = p-value for seeing the observed amount of overlap in this gene)

q = q-value, False Discovery Rate (Benjamini-Hochberg procedure)

Clustered Mutations

Table 5.  Get Full Table Genes with Clustered Mutations

num gene desc n mindist nmuts0 nmuts3 nmuts12 npairs0 npairs3 npairs12
2107 EGFR epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian) 92 0 304 377 411 304 377 411
7199 TP53 tumor protein p53 96 0 91 215 526 91 215 526
3152 IDH1 isocitrate dehydrogenase 1 (NADP+), soluble 14 0 91 91 91 91 91 91
5671 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 90 0 37 94 222 37 94 222
5319 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 33 0 11 32 44 11 32 44
5322 PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (alpha) 33 0 11 26 34 11 26 34
707 BRAF v-raf murine sarcoma viral oncogene homolog B1 6 0 10 10 15 10 10 15
3691 KRTAP4-11 keratin associated protein 4-11 9 0 6 9 13 6 9 13
4417 NBPF10 neuroblastoma breakpoint family, member 10 10 0 6 6 6 6 6 6
5816 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 HSA04115_P53_SIGNALING_PATHWAY Genes involved in p53 signaling pathway APAF1, ATM, ATR, BAI1, BAX, BBC3, BID, CASP3, CASP8, CASP9, CCNB1, CCNB2, CCNB3, CCND1, CCND2, CCND3, CCNE1, CCNE2, CCNG1, CCNG2, CD82, CDC2, CDK2, CDK4, CDK6, CDKN1A, CDKN2A, CHEK1, CHEK2, CYCS, DDB2, EI24, FAS, GADD45A, GADD45B, GADD45G, GTSE1, IGF1, IGFBP3, LRDD, MDM2, MDM4, P53AIP1, PERP, PMAIP1, PPM1D, PTEN, RCHY1, RFWD2, RPRM, RRM2, RRM2B, SCOTIN, SERPINB5, SERPINE1, SESN1, SESN2, SESN3, SFN, SIAH1, STEAP3, THBS1, TNFRSF10B, TP53, TP53I3, TP73, TSC2, ZMAT3 65 ATM(4), ATR(4), CASP9(1), CCNB3(2), CCND2(2), CCND3(1), CCNE1(1), CCNE2(1), CCNG1(2), CDKN1A(1), CDKN2A(2), CHEK1(3), CHEK2(1), DDB2(1), GADD45B(1), GTSE1(1), IGF1(2), LRDD(1), MDM2(2), MDM4(1), PPM1D(1), PTEN(90), RPRM(1), RRM2(1), SERPINB5(1), SERPINE1(2), SESN1(1), SESN3(1), SFN(1), THBS1(2), TP53(96), TSC2(4) 27921280 235 164 181 17 42 44 28 51 70 0 4.33e-14 <1.00e-15 <3.24e-14
2 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(33), PIK3R1(33), PTEN(90), PTK2B(3), PTPN11(4), PXN(1), RAF1(1), SOS1(3), SRC(2), STAT3(1) 18896094 192 150 164 5 21 37 25 38 71 0 <1.00e-15 <1.00e-15 <3.24e-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(1), EIF2S2(1), EIF2S3(2), GSK3B(1), IGF1(2), IGF1R(3), INPPL1(3), PIK3CA(33), PIK3R1(33), PTEN(90) 8404717 169 142 141 3 11 32 23 31 72 0 2.11e-14 <1.00e-15 <3.24e-14
4 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 63 AKT1(1), CDKN1B(1), CDKN2A(2), CREB1(1), ERBB4(1), GSK3B(1), IGF1(2), INPPL1(3), IRS1(4), IRS4(3), MET(3), MYC(1), PAK1(1), PAK3(1), PAK4(3), PAK7(1), PARD3(1), PIK3CA(33), PREX1(5), PTEN(90), RPS6KA1(1), RPS6KA2(2), RPS6KA3(1), SFN(1), SOS1(3), TSC2(4), YWHAE(2), YWHAH(1) 32949675 173 142 151 13 21 34 25 30 63 0 1.18e-09 <1.00e-15 <3.24e-14
5 EIF4PATHWAY The eIF-4F complex recognizes 5' mRNA caps, recruits RNA helicases, and maintains mRNA-ribosome bridging. AKT1, EIF4A1, EIF4A2, EIF4E, EIF4EBP1, EIF4G1, EIF4G2, EIF4G3, FRAP1, GHR, IRS1, MAPK1, MAPK14, MAPK3, MKNK1, PABPC1, PDK2, PDPK1, PIK3CA, PIK3R1, PRKCA, PRKCB1, PTEN, RPS6KB1 22 AKT1(1), EIF4A1(1), EIF4G1(1), EIF4G3(1), IRS1(4), MAPK1(2), MAPK3(1), PIK3CA(33), PIK3R1(33), PRKCA(1), PTEN(90) 11981597 168 138 140 4 13 33 23 29 70 0 2.18e-13 <1.00e-15 <3.24e-14
6 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(33), PIK3R1(33), PTEN(90), SOS1(3) 8259361 165 137 137 0 11 33 24 29 68 0 <1.00e-15 <1.00e-15 <3.24e-14
7 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(2), CDKN2A(2), MDM2(2), MYC(1), PIK3CA(33), PIK3R1(33), POLR1A(2), POLR1B(1), RB1(24), TP53(96) 8591371 196 136 146 2 36 27 24 38 70 1 <1.00e-15 <1.00e-15 <3.24e-14
8 G1PATHWAY CDK4/6-cyclin D and CDK2-cyclin E phosphorylate Rb, which allows the transcription of genes needed for the G1/S cell cycle transition. ABL1, ATM, ATR, CCNA1, CCND1, CCNE1, CDC2, CDC25A, CDK2, CDK4, CDK6, CDKN1A, CDKN1B, CDKN2A, CDKN2B, DHFR, E2F1, GSK3B, HDAC1, MADH3, MADH4, RB1, SKP2, TFDP1, TGFB1, TGFB2, TGFB3, TP53 25 ABL1(2), ATM(4), ATR(4), CCNA1(1), CCNE1(1), CDKN1A(1), CDKN1B(1), CDKN2A(2), CDKN2B(2), GSK3B(1), RB1(24), SKP2(1), TFDP1(1), TP53(96) 12803078 141 103 102 4 30 18 15 33 44 1 5.53e-13 <1.00e-15 <3.24e-14
9 P53PATHWAY p53 induces cell cycle arrest or apoptosis under conditions of DNA damage. APAF1, ATM, BAX, BCL2, CCND1, CCNE1, CDK2, CDK4, CDKN1A, E2F1, GADD45A, MDM2, PCNA, RB1, TIMP3, TP53 16 ATM(4), BCL2(2), CCNE1(1), CDKN1A(1), MDM2(2), RB1(24), TIMP3(1), TP53(96) 7755533 131 96 92 3 30 16 13 26 45 1 2.65e-12 <1.00e-15 <3.24e-14
10 RBPATHWAY The ATM protein kinase recognizes DNA damage and blocks cell cycle progression by phosphorylating chk1 and p53, which normally inhibits Rb to allow G1/S transitions. ATM, CDC2, CDC25A, CDC25B, CDC25C, CDK2, CDK4, CHEK1, MYT1, RB1, TP53, WEE1, YWHAH 12 ATM(4), CHEK1(3), RB1(24), TP53(96), WEE1(1), YWHAH(1) 7513078 129 95 90 2 30 15 14 27 42 1 1.07e-12 <1.00e-15 <3.24e-14

Table 7.  Get Full Table A Ranked List of Significantly Mutated Genesets (Excluding Significantly Mutated Genes). Number of significant genesets found: 0. Number of genesets displayed: 10

rank geneset description genes N_genes mut_tally N n npat nsite nsil n1 n2 n3 n4 n5 n6 p_ns_s p q
1 IL17PATHWAY Activated T cells secrete IL-17, which stimulates fibroblasts and other cells to secrete inflammatory and hematopoietic cytokines. CD2, CD34, CD3D, CD3E, CD3G, CD3Z, CD4, CD58, CD8A, CSF3, IL17, IL3, IL6, IL8, KITLG, TRA@, TRB@ 13 CD2(1), CD3E(2), CD3G(1), CD4(1), CD58(1), CD8A(1), IL3(1), IL6(1), KITLG(1) 2654041 10 10 10 1 3 1 1 3 2 0 0.15 0.0078 1
2 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) 1274247 6 6 6 1 2 1 1 0 2 0 0.34 0.0079 1
3 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) 2327767 12 12 12 2 5 2 0 4 1 0 0.18 0.0088 1
4 IFNGPATHWAY IFN gamma signaling pathway IFNG, IFNGR1, IFNGR2, JAK1, JAK2, STAT1 6 IFNG(2), IFNGR1(1), IFNGR2(3), JAK1(2), JAK2(2), STAT1(2) 3484295 12 12 12 0 0 0 3 6 3 0 0.057 0.01 1
5 ACE_INHIBITOR_PATHWAY_PHARMGKB ACE, AGT, AGTR1, AGTR2, BDKRB2, KNG1, NOS3, REN 8 ACE(5), AGT(1), AGTR1(1), AGTR2(1), KNG1(2), NOS3(3), REN(5) 4299288 18 18 17 2 10 2 0 2 4 0 0.04 0.012 1
6 NUCLEOTIDE_SUGARS_METABOLISM GALE, GALT, TGDS, UGDH, UXS1 5 GALE(2), GALT(1), TGDS(1), UGDH(1), UXS1(2) 1671876 7 7 7 0 1 1 1 2 2 0 0.14 0.014 1
7 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) 1368975 6 6 6 1 3 0 1 1 1 0 0.36 0.016 1
8 TCRMOLECULE T Cell Receptor and CD3 Complex CD3D, CD3E, CD3G, CD3Z, TRA@, TRB@ 3 CD3E(2), CD3G(1) 485067 3 3 3 0 0 0 1 1 1 0 0.42 0.016 1
9 HSA00472_D_ARGININE_AND_D_ORNITHINE_METABOLISM Genes involved in D-arginine and D-ornithine metabolism DAO 1 DAO(3) 307262 3 3 3 0 2 1 0 0 0 0 0.3 0.017 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) 1294076 5 5 5 0 2 1 1 0 1 0 0.2 0.033 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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