Mutation Analysis (MutSig v2.0)
Prostate Adenocarcinoma (Primary solid tumor)
28 January 2016  |  analyses__2016_01_28
Maintainer Information
Citation Information
doi:10.7908/C12R3R49
Maintained by David Heiman (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2016): Mutation Analysis (MutSig v2.0). Broad Institute of MIT and Harvard. doi:10.7908/C12R3R49
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: PRAD-TP

  • Number of patients in set: 498

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:PRAD-TP.final_analysis_set.maf

  • Blacklist used for this analysis: pancan_mutation_blacklist.v14.hg19.txt

  • Significantly mutated genes (q ≤ 0.1): 45

  • Mutations seen in COSMIC: 186

  • Significantly mutated genes in COSMIC territory: 10

  • Significantly mutated genesets: 25

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

Mutation Preprocessing

  • Read 498 MAFs of type "maf1"

  • Total number of mutations in input MAFs: 40678

  • After removing 34 mutations outside chr1-24: 40644

  • After removing 3109 blacklisted mutations: 37535

  • After removing 2580 noncoding mutations: 34955

  • After collapsing adjacent/redundant mutations: 32801

Mutation Filtering

  • Number of mutations before filtering: 32801

  • After removing 1852 mutations outside gene set: 30949

  • After removing 43 mutations outside category set: 30906

Results
Breakdown of Mutations by Type

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

type count
De_novo_Start_InFrame 17
De_novo_Start_OutOfFrame 25
Frame_Shift_Del 1026
Frame_Shift_Ins 318
In_Frame_Del 267
In_Frame_Ins 29
Missense_Mutation 19089
Nonsense_Mutation 1124
Nonstop_Mutation 12
Silent 7959
Splice_Site 1014
Start_Codon_Ins 1
Start_Codon_SNP 25
Total 30906
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 7290 797558419 9.1e-06 9.1 5.8 2.1
*Cp(A/C/T)->T 3942 6578860774 6e-07 0.6 0.38 1.7
A->G 2353 7121418846 3.3e-07 0.33 0.21 2.3
transver 5529 14497838039 3.8e-07 0.38 0.24 5
indel+null 3793 14497838039 2.6e-07 0.26 0.17 NaN
double_null 40 14497838039 2.8e-09 0.0028 0.0017 NaN
Total 22947 14497838039 1.6e-06 1.6 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). If the figure is unpopulated, then full coverage is assumed (e.g. MutSig CV doesn't use WIGs and assumes full coverage).

Figure 1. 

Distribution of Mutation Counts, Coverage, and Mutation Rates Across Samples

Figure 2.  Patients counts and rates file used to generate this plot: PRAD-TP.patients.counts_and_rates.txt

Lego Plots

The mutation spectrum is depicted in the lego plots below in which the 96 possible mutation types are subdivided into six large blocks, color-coded to reflect the base substitution type. Each large block is further subdivided into the 16 possible pairs of 5' and 3' neighbors, as listed in the 4x4 trinucleotide context legend. The height of each block corresponds to the mutation frequency for that kind of mutation (counts of mutations normalized by the base coverage in a given bin). The shape of the spectrum is a signature for dominant mutational mechanisms in different tumor types.

Figure 3.  Get High-res Image SNV Mutation rate lego plot for entire set. Each bin is normalized by base coverage for that bin. Colors represent the six SNV types on the upper right. The three-base context for each mutation is labeled in the 4x4 legend on the lower right. The fractional breakdown of SNV counts is shown in the pie chart on the upper left. If this figure is blank, not enough information was provided in the MAF to generate it.

Figure 4.  Get High-res Image SNV Mutation rate lego plots for 4 slices of mutation allele fraction (0<=AF<0.1, 0.1<=AF<0.25, 0.25<=AF<0.5, & 0.5<=AF) . The color code and three-base context legends are the same as the previous figure. If this figure is blank, not enough information was provided in the MAF to generate it.

CoMut Plot

Figure 5.  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: 45. 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_clust p_cons p_joint p q
1 SPOP speckle-type POZ protein 578042 58 57 19 0 1 2 11 42 2 0 <1.00e-15 6.4e-06 0 0.19 0 <1.00e-15 <1.64e-12
2 TP53 tumor protein p53 600130 59 57 44 0 17 7 8 10 16 1 2.00e-15 3.5e-07 2e-07 0.000029 0 <1.00e-15 <1.64e-12
3 FOXA1 forkhead box A1 522675 28 28 19 3 1 2 3 8 13 1 5.33e-15 0.27 0 0.042 0 <1.00e-15 <1.64e-12
4 CTNNB1 catenin (cadherin-associated protein), beta 1, 88kDa 1195076 13 13 10 0 1 2 3 7 0 0 3.64e-09 0.026 6e-07 0.021 0 <1.00e-15 <1.64e-12
5 MED12 mediator complex subunit 12 2619484 7 7 4 1 0 3 0 4 0 0 0.0216 0.34 0 0.12 0 <1.00e-15 <1.64e-12
6 C16orf62 chromosome 16 open reading frame 62 1480251 2 2 2 1 0 0 1 0 1 0 0.514 0.78 0.41 0 0 <1.00e-15 <1.64e-12
7 CLPTM1L CLPTM1-like 689916 3 2 3 0 1 1 0 0 1 0 0.251 0.18 0.35 0 0 <1.00e-15 <1.64e-12
8 DPYSL2 dihydropyrimidinase-like 2 868978 2 2 2 0 0 1 0 0 1 0 0.300 0.39 0.084 0 0 <1.00e-15 <1.64e-12
9 NEIL1 nei endonuclease VIII-like 1 (E. coli) 579143 2 2 2 0 0 1 0 0 1 0 0.215 0.42 0.34 0 0 <1.00e-15 <1.64e-12
10 SLC27A4 solute carrier family 27 (fatty acid transporter), member 4 958285 2 2 2 1 0 0 1 0 1 0 0.303 0.88 0.18 0 0 <1.00e-15 <1.64e-12
11 PITPNM2 phosphatidylinositol transfer protein, membrane-associated 2 1730968 2 1 2 0 1 0 0 0 1 0 0.924 0.42 0.73 0 0 <1.00e-15 <1.64e-12
12 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 583797 17 17 17 0 1 0 1 3 12 0 4.66e-15 0.16 0.15 0.87 0.26 4.35e-14 6.56e-11
13 ATM ataxia telangiectasia mutated 4658423 22 22 22 2 1 7 2 7 5 0 6.79e-08 0.14 0.56 0.017 0.072 9.78e-08 0.000136
14 EMG1 EMG1 nucleolar protein homolog (S. cerevisiae) 318405 4 4 2 0 0 0 0 0 4 0 0.000148 1 0.00026 0.9 0.00062 1.56e-06 0.00195
15 ETV3 ets variant gene 3 220292 5 5 5 0 0 1 1 1 2 0 2.78e-06 0.32 0.018 0.24 0.034 1.62e-06 0.00195
16 BRAF v-raf murine sarcoma viral oncogene homolog B1 1110102 8 8 7 0 0 0 2 5 1 0 2.41e-05 0.16 0.012 0.014 0.0051 2.08e-06 0.00235
17 NKX3-1 NK3 homeobox 1 251077 5 5 5 0 0 0 2 2 1 0 7.71e-06 0.42 0.15 0.0076 0.034 4.23e-06 0.00450
18 ZMYM3 zinc finger, MYM-type 3 1354589 13 12 13 0 2 0 0 4 7 0 5.02e-07 0.19 0.5 0.42 0.59 4.75e-06 0.00470
19 OR4P4 olfactory receptor, family 4, subfamily P, member 4 433858 5 5 4 0 3 0 0 1 1 0 3.75e-06 0.22 0.11 0.086 0.082 4.94e-06 0.00470
20 SALL1 sal-like 1 (Drosophila) 1959547 13 12 13 1 3 4 3 2 1 0 7.93e-06 0.032 0.026 0.56 0.042 5.35e-06 0.00484
21 IDH1 isocitrate dehydrogenase 1 (NADP+), soluble 631091 6 6 3 0 4 0 0 2 0 0 7.61e-05 0.17 0.0029 0.88 0.0055 6.53e-06 0.00563
22 KDM6A lysine (K)-specific demethylase 6A 1842539 13 13 13 2 2 0 1 1 9 0 4.74e-06 0.46 0.11 0.13 0.11 8.20e-06 0.00674
23 LMOD2 leiomodin 2 (cardiac) 484286 6 6 4 0 0 0 0 2 4 0 4.20e-06 0.7 0.66 0.044 0.14 8.85e-06 0.00696
24 MUC17 mucin 17, cell surface associated 6738064 33 31 31 7 2 17 2 10 2 0 1.38e-05 0.1 0.028 0.81 0.056 1.16e-05 0.00875
25 NTM neurotrimin 580556 7 7 7 0 2 2 0 1 2 0 1.33e-05 0.048 NaN NaN NaN 1.33e-05 0.00965
26 OR4D5 olfactory receptor, family 4, subfamily D, member 5 478550 6 6 6 0 3 2 0 1 0 0 1.04e-06 0.11 0.91 0.36 1 1.53e-05 0.0107
27 COL11A1 collagen, type XI, alpha 1 2802966 16 14 16 2 4 2 2 5 3 0 1.30e-05 0.13 0.083 0.28 0.12 2.29e-05 0.0153
28 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 1632682 16 14 13 2 3 4 3 6 0 0 5.06e-05 0.24 0.045 0.13 0.04 2.85e-05 0.0184
29 CDKN1B cyclin-dependent kinase inhibitor 1B (p27, Kip1) 300110 6 6 6 0 0 0 0 0 6 0 4.21e-06 0.71 0.5 0.36 0.54 3.20e-05 0.0199
30 NBPF1 neuroblastoma breakpoint family, member 1 1628419 15 11 15 2 0 6 1 4 3 1 3.58e-05 0.12 0.04 0.59 0.083 4.07e-05 0.0241
31 CANT1 calcium activated nucleotidase 1 527648 3 3 1 1 0 0 3 0 0 0 0.00813 0.8 0.00016 0.91 0.00037 4.14e-05 0.0241
32 OR5L2 olfactory receptor, family 5, subfamily L, member 2 467692 6 6 6 1 0 2 1 3 0 0 4.63e-06 0.35 0.48 0.58 0.68 4.31e-05 0.0244
33 BHLHE22 basic helix-loop-helix family, member e22 185955 3 3 2 0 0 0 0 0 3 0 0.000738 1 0.00097 0.97 0.0049 4.89e-05 0.0268
34 EPB41L3 erythrocyte membrane protein band 4.1-like 3 1660300 15 12 15 1 8 3 1 3 0 0 5.90e-06 0.017 0.47 0.83 0.65 5.18e-05 0.0276
35 LCE2D late cornified envelope 2D 167826 4 4 4 0 2 0 0 1 1 0 5.03e-06 0.68 0.96 0.21 0.89 5.95e-05 0.0307
SPOP

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

TP53

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

FOXA1

Figure S3.  This figure depicts the distribution of mutations and mutation types across the FOXA1 significant gene.

CTNNB1

Figure S4.  This figure depicts the distribution of mutations and mutation types across the CTNNB1 significant gene.

MED12

Figure S5.  This figure depicts the distribution of mutations and mutation types across the MED12 significant gene.

C16orf62

Figure S6.  This figure depicts the distribution of mutations and mutation types across the C16orf62 significant gene.

CLPTM1L

Figure S7.  This figure depicts the distribution of mutations and mutation types across the CLPTM1L significant gene.

DPYSL2

Figure S8.  This figure depicts the distribution of mutations and mutation types across the DPYSL2 significant gene.

NEIL1

Figure S9.  This figure depicts the distribution of mutations and mutation types across the NEIL1 significant gene.

SLC27A4

Figure S10.  This figure depicts the distribution of mutations and mutation types across the SLC27A4 significant gene.

PITPNM2

Figure S11.  This figure depicts the distribution of mutations and mutation types across the PITPNM2 significant gene.

PTEN

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

ATM

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

ETV3

Figure S14.  This figure depicts the distribution of mutations and mutation types across the ETV3 significant gene.

BRAF

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

NKX3-1

Figure S16.  This figure depicts the distribution of mutations and mutation types across the NKX3-1 significant gene.

ZMYM3

Figure S17.  This figure depicts the distribution of mutations and mutation types across the ZMYM3 significant gene.

OR4P4

Figure S18.  This figure depicts the distribution of mutations and mutation types across the OR4P4 significant gene.

SALL1

Figure S19.  This figure depicts the distribution of mutations and mutation types across the SALL1 significant gene.

IDH1

Figure S20.  This figure depicts the distribution of mutations and mutation types across the IDH1 significant gene.

KDM6A

Figure S21.  This figure depicts the distribution of mutations and mutation types across the KDM6A significant gene.

LMOD2

Figure S22.  This figure depicts the distribution of mutations and mutation types across the LMOD2 significant gene.

MUC17

Figure S23.  This figure depicts the distribution of mutations and mutation types across the MUC17 significant gene.

NTM

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

OR4D5

Figure S25.  This figure depicts the distribution of mutations and mutation types across the OR4D5 significant gene.

COL11A1

Figure S26.  This figure depicts the distribution of mutations and mutation types across the COL11A1 significant gene.

PIK3CA

Figure S27.  This figure depicts the distribution of mutations and mutation types across the PIK3CA significant gene.

CDKN1B

Figure S28.  This figure depicts the distribution of mutations and mutation types across the CDKN1B significant gene.

NBPF1

Figure S29.  This figure depicts the distribution of mutations and mutation types across the NBPF1 significant gene.

CANT1

Figure S30.  This figure depicts the distribution of mutations and mutation types across the CANT1 significant gene.

OR5L2

Figure S31.  This figure depicts the distribution of mutations and mutation types across the OR5L2 significant gene.

BHLHE22

Figure S32.  This figure depicts the distribution of mutations and mutation types across the BHLHE22 significant gene.

EPB41L3

Figure S33.  This figure depicts the distribution of mutations and mutation types across the EPB41L3 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: 10. Number of genes displayed: 10

rank gene description n cos n_cos N_cos cos_ev p q
1 TP53 tumor protein p53 59 356 56 177288 13449 0 0
2 IDH1 isocitrate dehydrogenase 1 (NADP+), soluble 6 5 5 2490 7460 4.1e-14 9.4e-11
3 CTNNB1 catenin (cadherin-associated protein), beta 1, 88kDa 13 138 11 68724 3981 8.3e-13 1.3e-09
4 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 16 220 14 109560 4270 1.2e-12 1.4e-09
5 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 17 767 17 381966 447 2.8e-12 2.6e-09
6 BRAF v-raf murine sarcoma viral oncogene homolog B1 8 89 6 44322 14422 1.6e-10 1.2e-07
7 SMAD4 SMAD family member 4 7 159 6 79182 25 4.8e-09 3.1e-06
8 APC adenomatous polyposis coli 10 839 8 417822 91 5.1e-07 0.00028
9 HRAS v-Ha-ras Harvey rat sarcoma viral oncogene homolog 4 19 3 9462 624 5.5e-07 0.00028
10 ATM ataxia telangiectasia mutated 22 245 4 122010 9 5e-05 0.022

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)

Geneset Analyses

Table 5.  Get Full Table A Ranked List of Significantly Mutated Genesets. (Source: MSigDB GSEA Cannonical Pathway Set).Number of significant genesets found: 25. 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 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(22), CDC25A(4), CDC25B(5), MYT1(2), RB1(3), TP53(59), WEE1(1) 13003593 96 82 81 5 24 16 11 19 24 2 2.8e-06 <1.00e-15 <2.05e-13
2 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 EIF2S1(1), NFKB1(3), RELA(3), TP53(59) 7150515 66 57 51 2 18 10 10 11 16 1 2.5e-06 <1.00e-15 <2.05e-13
3 ATMPATHWAY The tumor-suppressing protein kinase ATM responds to radiation-induced DNA damage by blocking cell-cycle progression and activating DNA repair. ABL1, ATM, BRCA1, CDKN1A, CHEK1, CHEK2, GADD45A, JUN, MAPK8, MDM2, MRE11A, NBS1, NFKB1, NFKBIA, RAD50, RAD51, RBBP8, RELA, TP53, TP73 19 ABL1(5), ATM(22), BRCA1(1), CDKN1A(2), MDM2(1), NFKB1(3), RAD50(1), RAD51(1), RBBP8(1), RELA(3), TP53(59), TP73(2) 22068537 101 79 86 7 24 18 13 21 24 1 7.2e-06 1.33e-15 2.05e-13
4 PLK3PATHWAY Active Plk3 phosphorylates CDC25c, blocking the G2/M transition, and phosphorylates p53 to induce apoptosis. ATM, ATR, CDC25C, CHEK1, CHEK2, CNK, TP53, YWHAH 7 ATM(22), ATR(3), TP53(59) 11869748 84 76 69 4 19 14 10 18 22 1 0.000028 1.33e-15 2.05e-13
5 TERTPATHWAY hTERC, the RNA subunit of telomerase, and hTERT, the catalytic protein subunit, are required for telomerase activity and are overexpressed in many cancers. HDAC1, MAX, MYC, SP1, SP3, TP53, WT1, ZNF42 7 HDAC1(1), MYC(1), SP1(2), SP3(3), TP53(59), WT1(2) 5195066 68 61 53 2 17 8 9 14 19 1 6.4e-07 2.22e-15 2.74e-13
6 TIDPATHWAY On ligand binding, interferon gamma receptors stimulate JAK2 kinase to phosphorylate STAT transcription factors, which promote expression of interferon responsive genes. DNAJA3, HSPA1A, IFNG, IFNGR1, IFNGR2, IKBKB, JAK2, LIN7A, NFKB1, NFKBIA, RB1, RELA, TIP-1, TNF, TNFRSF1A, TNFRSF1B, TP53, USH1C, WT1 18 IFNGR2(1), IKBKB(1), JAK2(1), NFKB1(3), RB1(3), RELA(3), TNF(1), TNFRSF1A(1), TNFRSF1B(1), TP53(59), USH1C(2), WT1(2) 13307491 78 63 63 4 21 13 11 12 19 2 1.2e-06 3.11e-15 3.03e-13
7 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 ARF1(1), CDKN1A(2), CDKN1B(6), CDKN2A(1), CFL1(1), E2F1(3), MDM2(1), TP53(59) 6200965 74 67 59 2 22 7 8 10 26 1 1.3e-06 3.44e-15 3.03e-13
8 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 APAF1(2), ATM(22), CDKN1A(2), E2F1(3), MDM2(1), PCNA(2), RB1(3), TP53(59) 13404960 94 81 79 4 22 16 11 18 25 2 4.3e-07 4.11e-15 3.16e-13
9 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(5), CDKN2A(1), E2F1(3), MDM2(1), MYC(1), PIK3CA(16), PIK3R1(2), POLR1A(3), POLR1B(3), POLR1C(2), RAC1(1), RB1(3), TP53(59) 15014619 100 81 82 4 26 13 14 22 23 2 4e-08 5.11e-15 3.50e-13
10 P53HYPOXIAPATHWAY Hypoxia induces p53 accumulation and consequent apoptosis with p53-mediated cell cycle arrest, which is present under conditions of DNA damage. ABCB1, AKT1, ATM, BAX, CDKN1A, CPB2, CSNK1A1, CSNK1D, FHL2, GADD45A, HIC1, HIF1A, HSPA1A, HSPCA, IGFBP3, MAPK8, MDM2, NFKBIB, NQO1, TP53 19 ABCB1(8), AKT1(3), ATM(22), CDKN1A(2), CPB2(1), HIC1(4), HIF1A(2), IGFBP3(1), MDM2(1), NFKBIB(2), NQO1(2), TP53(59) 15329723 107 91 91 6 29 21 11 21 24 1 1.5e-07 6.33e-15 3.90e-13

Table 6.  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 HSA00902_MONOTERPENOID_BIOSYNTHESIS Genes involved in monoterpenoid biosynthesis CYP2C19, CYP2C9 2 CYP2C19(4), CYP2C9(3) 1500904 7 6 7 0 3 1 1 2 0 0 0.15 0.0036 1
2 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 12 AKT1(3), CAT(2), GH1(3), GHR(1), HRAS(4), IGF1R(4), PIK3R1(2), SHC1(3), SOD2(1), SOD3(1) 8207519 24 23 21 2 6 4 6 5 3 0 0.02 0.004 1
3 HSA00130_UBIQUINONE_BIOSYNTHESIS Genes involved in ubiquinone biosynthesis COQ2, COQ3, COQ5, COQ6, COQ7, ND1, ND2, ND3, ND4, ND4L, ND5, ND6, NDUFA12, NDUFA13, NDUFB11 8 COQ3(2), COQ5(3), COQ7(1), NDUFA12(1), NDUFA13(2) 2929137 9 8 9 1 2 3 3 0 1 0 0.12 0.012 1
4 HSA00300_LYSINE_BIOSYNTHESIS Genes involved in lysine biosynthesis AADAT, AASDHPPT, AASS, KARS 4 AADAT(2), AASDHPPT(1), AASS(3), KARS(2) 3479933 8 8 8 1 0 2 2 3 1 0 0.31 0.023 1
5 CAPROLACTAM_DEGRADATION AKR1A1, ECHS1, EHHADH, HADHA, SDS 5 AKR1A1(2), ECHS1(1), EHHADH(5), SDS(1) 3557117 9 9 9 1 3 2 0 3 1 0 0.21 0.023 1
6 LYSINE_BIOSYNTHESIS AADAT, AASDH, AASDHPPT, AASS, KARS 5 AADAT(2), AASDH(2), AASDHPPT(1), AASS(3), KARS(2) 5143805 10 10 10 1 0 2 2 4 2 0 0.26 0.026 1
7 HSA00930_CAPROLACTAM_DEGRADATION Genes involved in caprolactam degradation AKR1A1, ASAHL, ECHS1, EHHADH, HADH, HADHA, HSD17B10, HSD17B4, NTAN1, SIRT1, SIRT2, SIRT5, SIRT7, VNN2, VNN3 13 AKR1A1(2), ECHS1(1), EHHADH(5), HADH(3), HSD17B4(3), SIRT1(3), SIRT2(1), SIRT5(1), VNN2(1) 8706167 20 18 20 2 8 4 1 5 2 0 0.042 0.027 1
8 SA_G2_AND_M_PHASES Cdc25 activates the cdc2/cyclin B complex to induce the G2/M transition. CDC2, CDC25A, CDC25B, CDK7, CDKN1A, CHEK1, NEK1, WEE1 7 CDC25A(4), CDC25B(5), CDK7(2), CDKN1A(2), NEK1(3), WEE1(1) 5092069 17 13 17 2 8 2 0 2 5 0 0.19 0.11 1
9 ETCPATHWAY Energy is extracted from carbohydrates via oxidation and transferred to the mitochondrial electron transport chain, which couples ATP synthesis to the reduction of oxygen to water. ATP5A1, CYCS, GPD2, MTCO1, NDUFA1, SDHA, SDHB, SDHC, SDHD, UQCRC1 9 ATP5A1(2), GPD2(1), SDHA(3), SDHB(2), SDHC(2), UQCRC1(2) 4880809 12 9 12 0 0 5 1 2 4 0 0.019 0.12 1
10 HYPERTROPHY_MODEL ADAM10, ANKRD1, ATF3, CYR61, DUSP14, EIF4E, EIF4EBP1, GDF8, HBEGF, IFNG, IFRD1, IL18, IL1A, IL1R1, JUND, MYOG, NR4A3, TCF8, VEGF, WDR1 17 ADAM10(2), ANKRD1(1), ATF3(1), CYR61(1), DUSP14(1), EIF4E(1), IFRD1(1), IL1A(1), JUND(2), NR4A3(5), WDR1(1) 7921832 17 12 17 1 2 6 4 4 1 0 0.019 0.12 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

In addition to the links below, the full results of the analysis summarized in this report can also be downloaded programmatically using firehose_get, or interactively from either the Broad GDAC website or TCGA Data Coordination Center Portal.

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