Mutation Analysis (MutSig v2.0)
Stomach Adenocarcinoma (Primary solid tumor)
28 January 2016  |  analyses__2016_01_28
Maintainer Information
Citation Information
doi:10.7908/C1H131GW
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/C1H131GW
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: STAD-TP

  • Number of patients in set: 395

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:STAD-TP.final_analysis_set.maf

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

  • Significantly mutated genes (q ≤ 0.1): 206

  • Mutations seen in COSMIC: 852

  • Significantly mutated genes in COSMIC territory: 62

  • Significantly mutated genesets: 21

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

Mutation Preprocessing

  • Read 395 MAFs of type "maf1"

  • Total number of mutations in input MAFs: 208988

  • After removing 103 mutations outside chr1-24: 208885

  • After removing 7493 blacklisted mutations: 201392

  • After removing 15358 noncoding mutations: 186034

  • After collapsing adjacent/redundant mutations: 177223

Mutation Filtering

  • Number of mutations before filtering: 177223

  • After removing 9712 mutations outside gene set: 167511

  • After removing 747 mutations outside category set: 166764

  • After removing 4 "impossible" mutations in

  • gene-patient-category bins of zero coverage: 156301

Results
Breakdown of Mutations by Type

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

type count
De_novo_Start_InFrame 23
De_novo_Start_OutOfFrame 45
Frame_Shift_Del 13976
Frame_Shift_Ins 3838
In_Frame_Del 1248
In_Frame_Ins 192
Missense_Mutation 98594
Nonsense_Mutation 5211
Nonstop_Mutation 101
Silent 38054
Splice_Site 5307
Start_Codon_Del 27
Start_Codon_Ins 10
Start_Codon_SNP 99
Stop_Codon_Del 29
Stop_Codon_Ins 10
Total 166764
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 36974 639196665 0.000058 58 5.2 2.1
*Cp(A/C/T)->T 16505 5250451690 3.1e-06 3.1 0.28 1.7
A->G 17072 5670926268 3e-06 3 0.27 2.3
transver 28140 11560574623 2.4e-06 2.4 0.22 5
indel+null 29306 11560574623 2.5e-06 2.5 0.23 NaN
double_null 711 11560574623 6.2e-08 0.062 0.0055 NaN
Total 128708 11560574623 0.000011 11 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: STAD-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.

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: 206. 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 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 1293660 80 65 35 2 13 27 27 10 3 0 7.99e-15 2.04e-09 0.000016 0.0018 2.6e-06 0.000 0.000
2 TP53 tumor protein p53 483681 200 190 112 2 57 22 20 30 69 2 <1.00e-15 <1.00e-15 0 0 0 <1.00e-15 <5.32e-13
3 RNF43 ring finger protein 43 858239 56 45 23 2 3 4 3 1 38 7 9.33e-15 0.0676 0 0.38 0 <1.00e-15 <5.32e-13
4 PGM5 phosphoglucomutase 5 543793 41 39 9 3 8 0 25 1 7 0 1.04e-14 0.000510 0 1 0 <1.00e-15 <5.32e-13
5 KRT75 keratin 75 665820 40 38 10 3 3 3 1 31 2 0 6.66e-15 0.0103 0 0.083 0 <1.00e-15 <5.32e-13
6 XYLT2 xylosyltransferase II 889238 43 38 15 5 8 1 3 0 30 1 4.10e-06 0.595 0 0.97 0 <1.00e-15 <5.32e-13
7 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 271649 37 37 6 0 0 30 0 7 0 0 3.89e-15 2.65e-05 0 0.0032 0 <1.00e-15 <5.32e-13
8 ZBTB20 zinc finger and BTB domain containing 20 803913 45 37 17 11 9 4 2 1 28 1 0.0716 0.782 0 0.92 0 <1.00e-15 <5.32e-13
9 BRD8 bromodomain containing 8 1615552 35 34 12 1 2 2 1 27 3 0 1.68e-08 0.00307 0 1 0 <1.00e-15 <5.32e-13
10 CDH1 cadherin 1, type 1, E-cadherin (epithelial) 1003383 33 32 29 3 3 6 6 11 7 0 1.31e-14 0.00501 0.000026 0.0003 0 <1.00e-15 <5.32e-13
11 FHOD3 formin homology 2 domain containing 3 1634806 35 30 22 2 9 3 2 4 17 0 0.00169 0.0175 0.000059 0.00058 0 <1.00e-15 <5.32e-13
12 LARP4B La ribonucleoprotein domain family, member 4B 882273 33 30 12 3 3 1 1 1 27 0 9.50e-06 0.357 0 0.74 0 <1.00e-15 <5.32e-13
13 SMAD4 SMAD family member 4 667940 31 28 25 1 7 6 0 12 5 1 3.66e-15 0.00737 0 0.4 0 <1.00e-15 <5.32e-13
14 MCM8 minichromosome maintenance complex component 8 1023288 29 27 12 4 2 19 4 3 1 0 3.95e-06 0.0483 0 0.0068 0 <1.00e-15 <5.32e-13
15 P4HTM prolyl 4-hydroxylase, transmembrane (endoplasmic reticulum) 546563 27 26 8 1 4 1 1 21 0 0 1.24e-11 0.00771 0 1 0 <1.00e-15 <5.32e-13
16 CBWD1 COBW domain containing 1 385130 22 21 3 2 0 0 1 1 20 0 4.01e-08 0.232 0 4e-07 0 <1.00e-15 <5.32e-13
17 FRMD4A FERM domain containing 4A 1108415 21 21 9 3 4 2 0 0 14 1 0.110 0.420 0.000012 0.00035 0 <1.00e-15 <5.32e-13
18 RHOA ras homolog gene family, member A 236210 20 19 15 0 2 4 4 9 1 0 1.08e-14 0.00434 0 0.54 0 <1.00e-15 <5.32e-13
19 ZBTB7C zinc finger and BTB domain containing 7C 598537 19 17 9 7 3 1 0 0 15 0 0.0266 0.995 4e-07 0.002 0 <1.00e-15 <5.32e-13
20 DDX17 DEAD (Asp-Glu-Ala-Asp) box polypeptide 17 797836 15 15 5 1 1 0 0 1 13 0 0.0658 0.898 0 1 0 <1.00e-15 <5.32e-13
21 MVK mevalonate kinase 473133 15 15 6 1 1 1 0 3 10 0 0.00268 0.417 1e-05 0.0001 0 <1.00e-15 <5.32e-13
22 GLT6D1 glycosyltransferase 6 domain containing 1 333346 14 14 5 2 0 0 1 12 1 0 2.97e-07 0.356 0.000018 0 0 <1.00e-15 <5.32e-13
23 HOXD8 homeobox D8 249415 14 13 6 1 0 0 0 2 10 2 5.90e-05 0.854 0 0.97 0 <1.00e-15 <5.32e-13
24 GNG12 guanine nucleotide binding protein (G protein), gamma 12 89651 12 12 4 2 0 1 1 0 10 0 1.06e-07 0.812 2e-07 0.33 0 <1.00e-15 <5.32e-13
25 WNT16 wingless-type MMTV integration site family, member 16 446967 14 12 6 1 2 1 1 1 9 0 0.0105 0.364 0.00023 1.6e-06 0 <1.00e-15 <5.32e-13
26 GAB2 GRB2-associated binding protein 2 806322 12 11 6 6 1 0 1 8 2 0 0.997 0.960 0.000012 0.0013 0 <1.00e-15 <5.32e-13
27 PLA2G1B phospholipase A2, group IB (pancreas) 182885 8 8 1 0 0 0 0 8 0 0 4.77e-05 0.316 0 0.89 0 <1.00e-15 <5.32e-13
28 KLRK1 killer cell lectin-like receptor subfamily K, member 1 260202 5 5 1 1 0 0 0 0 5 0 0.149 1.000 0 0.091 0 <1.00e-15 <5.32e-13
29 RHOQ ras homolog gene family, member Q 250532 5 5 1 0 0 0 0 0 5 0 0.218 1.000 0 1 0 <1.00e-15 <5.32e-13
30 HIATL1 hippocampus abundant transcript-like 1 569276 4 4 4 0 1 0 0 1 2 0 0.865 0.151 0.2 0 0 <1.00e-15 <5.32e-13
31 DOLPP1 dolichyl pyrophosphate phosphatase 1 295684 3 3 3 0 2 0 0 0 1 0 0.704 0.212 0.8 0 0 <1.00e-15 <5.32e-13
32 CDK1 cyclin-dependent kinase 1 365539 2 2 2 0 0 0 0 0 2 0 0.663 0.899 0.24 0 0 <1.00e-15 <5.32e-13
33 RAB4B RAB4B, member RAS oncogene family 251808 2 2 2 0 0 0 0 1 1 0 0.551 0.577 0.16 0 0 <1.00e-15 <5.32e-13
34 ROPN1B ropporin, rhophilin associated protein 1B 245810 2 2 2 1 1 0 0 0 1 0 0.712 0.711 0.89 0 0 <1.00e-15 <5.32e-13
35 B2M beta-2-microglobulin 146873 23 18 16 1 0 2 2 2 12 5 1.31e-14 0.155 0.0082 0.66 0.018 8.77e-15 4.54e-12
PIK3CA

Figure S1.  This figure depicts the distribution of mutations and mutation types across the PIK3CA significant gene.

TP53

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

RNF43

Figure S3.  This figure depicts the distribution of mutations and mutation types across the RNF43 significant gene.

PGM5

Figure S4.  This figure depicts the distribution of mutations and mutation types across the PGM5 significant gene.

KRT75

Figure S5.  This figure depicts the distribution of mutations and mutation types across the KRT75 significant gene.

XYLT2

Figure S6.  This figure depicts the distribution of mutations and mutation types across the XYLT2 significant gene.

KRAS

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

ZBTB20

Figure S8.  This figure depicts the distribution of mutations and mutation types across the ZBTB20 significant gene.

BRD8

Figure S9.  This figure depicts the distribution of mutations and mutation types across the BRD8 significant gene.

CDH1

Figure S10.  This figure depicts the distribution of mutations and mutation types across the CDH1 significant gene.

FHOD3

Figure S11.  This figure depicts the distribution of mutations and mutation types across the FHOD3 significant gene.

LARP4B

Figure S12.  This figure depicts the distribution of mutations and mutation types across the LARP4B significant gene.

SMAD4

Figure S13.  This figure depicts the distribution of mutations and mutation types across the SMAD4 significant gene.

MCM8

Figure S14.  This figure depicts the distribution of mutations and mutation types across the MCM8 significant gene.

P4HTM

Figure S15.  This figure depicts the distribution of mutations and mutation types across the P4HTM significant gene.

CBWD1

Figure S16.  This figure depicts the distribution of mutations and mutation types across the CBWD1 significant gene.

FRMD4A

Figure S17.  This figure depicts the distribution of mutations and mutation types across the FRMD4A significant gene.

RHOA

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

ZBTB7C

Figure S19.  This figure depicts the distribution of mutations and mutation types across the ZBTB7C significant gene.

DDX17

Figure S20.  This figure depicts the distribution of mutations and mutation types across the DDX17 significant gene.

MVK

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

GLT6D1

Figure S22.  This figure depicts the distribution of mutations and mutation types across the GLT6D1 significant gene.

HOXD8

Figure S23.  This figure depicts the distribution of mutations and mutation types across the HOXD8 significant gene.

GNG12

Figure S24.  This figure depicts the distribution of mutations and mutation types across the GNG12 significant gene.

WNT16

Figure S25.  This figure depicts the distribution of mutations and mutation types across the WNT16 significant gene.

GAB2

Figure S26.  This figure depicts the distribution of mutations and mutation types across the GAB2 significant gene.

PLA2G1B

Figure S27.  This figure depicts the distribution of mutations and mutation types across the PLA2G1B significant gene.

KLRK1

Figure S28.  This figure depicts the distribution of mutations and mutation types across the KLRK1 significant gene.

RHOQ

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

HIATL1

Figure S30.  This figure depicts the distribution of mutations and mutation types across the HIATL1 significant gene.

DOLPP1

Figure S31.  This figure depicts the distribution of mutations and mutation types across the DOLPP1 significant gene.

CDK1

Figure S32.  This figure depicts the distribution of mutations and mutation types across the CDK1 significant gene.

RAB4B

Figure S33.  This figure depicts the distribution of mutations and mutation types across the RAB4B significant gene.

ROPN1B

Figure S34.  This figure depicts the distribution of mutations and mutation types across the ROPN1B 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: 62. Number of genes displayed: 10

rank gene description n cos n_cos N_cos cos_ev p q
1 TP53 tumor protein p53 200 356 188 140620 51271 0 0
2 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 36 767 36 302965 1199 0 0
3 ERBB3 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) 43 6 8 2370 8 8.9e-14 1.3e-10
4 APC adenomatous polyposis coli 53 839 27 331405 599 3.2e-13 3.7e-10
5 ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian) 23 42 10 16590 84 5.4e-13 4.1e-10
6 NOS3 nitric oxide synthase 3 (endothelial cell) 15 6 6 2370 6 5.4e-13 4.1e-10
7 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 37 52 36 20540 303856 6.3e-13 4.1e-10
8 FBXW7 F-box and WD repeat domain containing 7 32 91 20 35945 1084 9.3e-13 5.2e-10
9 SMAD4 SMAD family member 4 31 159 26 62805 92 1.2e-12 5.2e-10
10 CDH1 cadherin 1, type 1, E-cadherin (epithelial) 33 185 17 73075 55 1.2e-12 5.2e-10

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: 21. 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(10), CDKN2A(17), E2F1(4), MDM2(8), MYC(6), PIK3CA(80), PIK3R1(12), POLR1A(19), POLR1B(8), POLR1C(4), POLR1D(4), RAC1(1), RB1(14), TBX2(10), TP53(200), TWIST1(3) 11920579 400 265 261 39 100 58 65 60 112 5 <1.00e-15 <1.00e-15 <1.03e-13
2 ATRBRCAPATHWAY BRCA1 and 2 block cell cycle progression in response to DNA damage and promote double-stranded break repair; mutations induce breast cancer susceptibility. ATM, ATR, BRCA1, BRCA2, CHEK1, CHEK2, FANCA, FANCC, FANCD2, FANCE, FANCF, FANCG, HUS1, MRE11A, NBS1, RAD1, RAD17, RAD50, RAD51, RAD9A, TP53, TREX1 21 ATM(49), ATR(28), BRCA1(16), BRCA2(39), CHEK1(6), CHEK2(10), FANCA(12), FANCC(6), FANCD2(14), FANCE(6), FANCF(1), FANCG(4), HUS1(2), MRE11A(7), RAD1(2), RAD17(6), RAD50(12), RAD51(1), RAD9A(5), TP53(200), TREX1(4) 25906136 430 254 328 43 96 51 49 71 153 10 1.26e-12 <1.00e-15 <1.03e-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(10), ATM(49), BRCA1(16), CDKN1A(5), CHEK1(6), CHEK2(10), JUN(5), MAPK8(6), MDM2(8), MRE11A(7), NFKB1(8), NFKBIA(1), RAD50(12), RAD51(1), RBBP8(5), RELA(7), TP53(200), TP73(6) 17491262 362 248 262 38 86 42 40 60 128 6 1.31e-11 <1.00e-15 <1.03e-13
4 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(33), AKT1(3), ATM(49), BAX(1), CDKN1A(5), CPB2(10), CSNK1A1(5), CSNK1D(4), FHL2(2), HIC1(10), HIF1A(5), HSPA1A(4), IGFBP3(5), MAPK8(6), MDM2(8), NFKBIB(8), NQO1(3), TP53(200) 12175875 361 248 265 32 95 48 36 61 115 6 <1.00e-15 <1.00e-15 <1.03e-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(9), MAX(3), MYC(6), SP1(5), SP3(5), TP53(200), WT1(5) 4140585 233 206 143 11 68 28 23 35 77 2 <1.00e-15 <1.00e-15 <1.03e-13
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(5), DNAJC3(3), EIF2S1(2), EIF2S2(3), NFKB1(8), NFKBIA(1), RELA(7), TP53(200) 5730250 229 200 141 10 62 26 23 39 77 2 <1.00e-15 <1.00e-15 <1.03e-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(5), CCND1(2), CDK2(4), CDK4(2), CDKN1A(5), CDKN1B(1), CDKN2A(17), CFL1(1), E2F1(4), E2F2(5), MDM2(8), NXT1(3), PRB1(3), TP53(200) 4941636 260 213 168 17 73 34 26 39 84 4 <1.00e-15 1.67e-15 1.47e-13
8 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(3), APAF1(8), ATM(49), BAD(4), BAX(1), BCL2(4), BCL2L1(1), BID(2), CASP3(2), CASP6(1), CASP7(4), CASP9(3), EIF2S1(2), PRKCA(8), PTK2(11), PXN(6), STAT1(11), TLN1(28), TP53(200) 16068160 348 244 253 28 102 47 35 53 106 5 <1.00e-15 2.22e-15 1.64e-13
9 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(49), ATR(28), CDC25C(11), CHEK1(6), CHEK2(10), TP53(200), YWHAH(3) 9392938 307 232 211 22 78 32 33 51 107 6 9.74e-12 2.44e-15 1.64e-13
10 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 DNAJA3(5), HSPA1A(4), IFNG(2), IFNGR1(10), IFNGR2(2), IKBKB(10), JAK2(12), LIN7A(9), NFKB1(8), NFKBIA(1), RB1(14), RELA(7), TNF(3), TNFRSF1A(6), TNFRSF1B(3), TP53(200), USH1C(8), WT1(5) 10636090 309 226 219 41 83 39 32 54 98 3 4.05e-10 2.66e-15 1.64e-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 SLRPPATHWAY Small leucine-rich proteoglycans (SLRPs) interact with and reorganize collagen fibers in the extracellular matrix. BGN, DCN, DSPG3, FMOD, KERA, LUM 5 BGN(1), DCN(10), FMOD(12), KERA(5), LUM(8) 2129598 36 29 36 4 14 2 4 12 4 0 0.013 0.16 1
2 FOSBPATHWAY FOSB gene expression and drug abuse CDK5, FOSB, GRIA2, JUND, PPP1R1B 5 CDK5(3), FOSB(7), GRIA2(26), JUND(2), PPP1R1B(3) 2191409 41 34 41 7 8 9 6 11 7 0 0.032 0.21 1
3 HSA00785_LIPOIC_ACID_METABOLISM Genes involved in lipoic acid metabolism LIAS, LIPT1, LOC387787 2 LIAS(4), LIPT1(5) 895003 9 9 8 1 2 3 1 0 2 1 0.21 0.42 1
4 HSA00643_STYRENE_DEGRADATION Genes involved in styrene degradation FAH, GSTZ1, HGD 3 FAH(7), GSTZ1(2), HGD(6) 1306926 15 15 13 3 4 0 3 4 4 0 0.4 0.53 1
5 HSA03060_PROTEIN_EXPORT Genes involved in protein export OXA1L, SEC61A2, SRP19, SRP54, SRP68, SRP72, SRP9, SRPR 8 OXA1L(3), SEC61A2(4), SRP19(3), SRP54(6), SRP68(6), SRP72(14), SRP9(2), SRPR(16) 4424708 54 42 52 5 15 7 10 5 17 0 0.0031 0.68 1
6 NUCLEOTIDE_SUGARS_METABOLISM GALE, GALT, TGDS, UGDH, UXS1 5 GALE(1), GALT(3), TGDS(5), UGDH(8), UXS1(8) 2256701 25 22 25 3 9 2 6 4 4 0 0.033 0.69 1
7 HSA00031_INOSITOL_METABOLISM Genes involved in inositol metabolism ALDH6A1, TPI1 2 ALDH6A1(6), TPI1(3) 965217 9 9 9 2 4 2 1 1 1 0 0.36 0.7 1
8 INOSITOL_METABOLISM ALDH6A1, ALDOA, ALDOB, ALDOC, TPI1 5 ALDH6A1(6), ALDOA(1), ALDOB(9), ALDOC(7), TPI1(3) 2295817 26 25 26 4 6 7 3 6 4 0 0.061 0.78 1
9 TERPENOID_BIOSYNTHESIS FDFT1, FDPS, FDPS, LOC402397, IDI1, SQLE 4 FDFT1(3), FDPS(12), IDI1(2), SQLE(9) 1868455 26 19 25 3 7 3 3 4 9 0 0.05 0.78 1
10 HSA00520_NUCLEOTIDE_SUGARS_METABOLISM Genes involved in nucleotide sugars metabolism GALE, GALT, TGDS, UGDH, UGP2, UXS1 6 GALE(1), GALT(3), TGDS(5), UGDH(8), UGP2(9), UXS1(8) 2875221 34 27 33 4 11 2 6 6 9 0 0.028 0.78 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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