Acute Myeloid Leukemia: Mutation Analysis (MutSig v2.0)
(primary blood tumor (peripheral) cohort)
Maintained by Dan DiCara (Broad Institute)
Overview
Introduction

This report serves to describe the mutational landscape and properties of a given individual set, as well as rank genes and genesets according to mutational significance. MutSig v2.0 was used to generate the results found in this report.

  • Working with individual set: LAML-TB

  • Number of patients in set: 196

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:LAML-TB.final_analysis_set.maf

  • Significantly mutated genes (q ≤ 0.1): 37

  • Mutations seen in COSMIC: 229

  • Significantly mutated genes in COSMIC territory: 18

  • Genes with clustered mutations (≤ 3 aa apart): 31

  • Significantly mutated genesets: 64

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

Mutation Preprocessing

  • Read 196 MAFs of type "WashU"

  • Total number of mutations in input MAFs: 5500

  • After removing 96 mutations outside chr1-24: 5404

  • After removing 1 blacklisted mutations: 5403

  • After removing 376 noncoding mutations: 5027

  • After collapsing adjacent/redundant mutations: 5021

Mutation Filtering

  • Number of mutations before filtering: 5021

  • After removing 624 mutations outside gene set: 4397

  • After removing 10 mutations outside category set: 4387

Results
Breakdown of Mutations by Type

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

type count
Frame_Shift_Del 99
Frame_Shift_Ins 114
In_Frame_Del 95
In_Frame_Ins 58
Missense_Mutation 2676
Nonsense_Mutation 188
Nonstop_Mutation 2
Silent 1053
Splice_Site 102
Total 4387
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
*CpG->T 782 270928448 2.9e-06 2.9 4.7
*Cp(A/C/T)->T 682 2455562676 2.8e-07 0.28 0.45
A->G 357 2731323896 1.3e-07 0.13 0.21
transver 853 5457815020 1.6e-07 0.16 0.26
indel+null 651 5457815216 1.2e-07 0.12 0.2
double_null 9 5457815216 1.6e-09 0.0016 0.0027
Total 3334 5457815216 6.1e-07 0.61 1
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: LAML-TB.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_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: 37. 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_cons p_joint p q
1 DNMT3A DNA (cytosine-5-)-methyltransferase 3 alpha 510188 54 49 28 0 32 2 2 4 14 0 <1.00e-15 NaN NaN <1.00e-15 <8.64e-12
2 NPM1 nucleophosmin (nucleolar phosphoprotein B23, numatrin) 182476 47 47 1 0 0 0 0 0 47 0 <1.00e-15 NaN NaN <1.00e-15 <8.64e-12
3 TP53 tumor protein p53 256956 14 11 14 1 3 2 3 1 5 0 3.44e-15 NaN NaN 3.44e-15 1.38e-11
4 FLT3 fms-related tyrosine kinase 3 594076 53 52 29 0 0 1 1 16 35 0 3.66e-15 NaN NaN 3.66e-15 1.38e-11
5 IDH1 isocitrate dehydrogenase 1 (NADP+), soluble 250292 20 20 2 0 18 0 0 2 0 0 4.00e-15 NaN NaN 4.00e-15 1.38e-11
6 NRAS neuroblastoma RAS viral (v-ras) oncogene homolog 114856 18 18 6 0 0 9 1 8 0 0 5.11e-15 NaN NaN 5.11e-15 1.39e-11
7 RUNX1 runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene) 144452 19 17 16 0 1 3 2 3 9 1 5.77e-15 NaN NaN 5.77e-15 1.39e-11
8 IDH2 isocitrate dehydrogenase 2 (NADP+), mitochondrial 229124 18 18 2 0 15 2 0 1 0 0 6.44e-15 NaN NaN 6.44e-15 1.39e-11
9 WT1 Wilms tumor 1 163856 12 12 8 0 1 1 0 0 9 1 7.44e-15 NaN NaN 7.44e-15 1.43e-11
10 TET2 tet oncogene family member 2 686392 17 15 17 1 0 1 0 2 9 5 9.55e-15 NaN NaN 9.55e-15 1.44e-11
11 U2AF1 U2 small nuclear RNA auxiliary factor 1 152488 10 10 3 0 0 6 0 4 0 0 9.77e-15 NaN NaN 9.77e-15 1.44e-11
12 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 138572 8 8 4 0 0 4 1 3 0 0 9.99e-15 NaN NaN 9.99e-15 1.44e-11
13 PHF6 PHD finger protein 6 242844 6 6 6 0 0 1 0 1 4 0 4.05e-10 NaN NaN 4.05e-10 5.38e-07
14 PTPN11 protein tyrosine phosphatase, non-receptor type 11 (Noonan syndrome 1) 357504 7 7 6 0 0 3 1 3 0 0 4.84e-10 NaN NaN 4.84e-10 5.97e-07
15 KIT v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog 582316 8 7 5 0 1 0 0 5 2 0 4.31e-09 NaN NaN 4.31e-09 4.97e-06
16 C17orf97 chromosome 17 open reading frame 97 166012 5 5 4 1 0 0 1 4 0 0 1.37e-08 NaN NaN 1.37e-08 1.48e-05
17 ETV6 ets variant gene 6 (TEL oncogene) 272636 5 5 5 0 0 0 1 1 3 0 5.80e-08 NaN NaN 5.80e-08 5.89e-05
18 SMC3 structural maintenance of chromosomes 3 735196 6 6 6 0 1 1 1 1 2 0 3.94e-07 NaN NaN 3.94e-07 0.000378
19 FAM5C family with sequence similarity 5, member C 456484 6 5 6 0 4 1 0 1 0 0 6.32e-07 NaN NaN 6.32e-07 0.000574
20 MUC4 mucin 4, cell surface associated 987448 10 7 8 6 1 0 1 5 3 0 1.26e-06 NaN NaN 1.26e-06 0.00109
21 CYP21A2 cytochrome P450, family 21, subfamily A, polypeptide 2 202468 4 4 1 0 0 4 0 0 0 0 2.62e-06 NaN NaN 2.62e-06 0.00216
22 NOTCH2NL Notch homolog 2 (Drosophila) N-terminal like 142492 3 3 2 0 0 0 0 0 3 0 5.34e-06 NaN NaN 5.34e-06 0.00419
23 AP3S1 adaptor-related protein complex 3, sigma 1 subunit 104468 3 3 1 0 0 0 0 0 3 0 1.02e-05 NaN NaN 1.02e-05 0.00765
24 SMC1A structural maintenance of chromosomes 1A 741076 5 5 5 0 1 0 1 2 1 0 1.22e-05 NaN NaN 1.22e-05 0.00875
25 TRIM48 tripartite motif-containing 48 126812 3 3 2 0 0 0 2 1 0 0 2.26e-05 NaN NaN 2.26e-05 0.0156
26 C5orf25 chromosome 5 open reading frame 25 250292 3 3 2 0 1 2 0 0 0 0 2.56e-05 NaN NaN 2.56e-05 0.0170
27 CCDC74A coiled-coil domain containing 74A 165620 3 3 2 0 1 2 0 0 0 0 3.61e-05 NaN NaN 3.61e-05 0.0231
28 OR11H12 olfactory receptor, family 11, subfamily H, member 12 193060 3 3 3 0 0 1 1 1 0 0 6.25e-05 NaN NaN 6.25e-05 0.0386
29 OR5H6 olfactory receptor, family 5, subfamily H, member 6 192472 3 3 1 2 0 0 0 0 3 0 0.000115 NaN NaN 0.000115 0.0686
30 STAG2 stromal antigen 2 772044 4 4 4 0 0 0 0 0 4 0 0.000144 NaN NaN 0.000144 0.0794
31 SUZ12 suppressor of zeste 12 homolog (Drosophila) 393176 3 3 3 0 1 1 0 0 1 0 0.000145 NaN NaN 0.000145 0.0794
32 NMUR2 neuromedin U receptor 2 247744 3 3 3 0 2 1 0 0 0 0 0.000148 NaN NaN 0.000148 0.0794
33 HLA-B major histocompatibility complex, class I, B 113484 2 2 2 0 0 0 0 1 1 0 0.000159 NaN NaN 0.000159 0.0794
34 FAM57B family with sequence similarity 57, member B 77224 2 2 2 0 1 0 0 0 1 0 0.000160 NaN NaN 0.000160 0.0794
35 LILRA3 leukocyte immunoglobulin-like receptor, subfamily A (without TM domain), member 3 264208 3 3 1 1 0 0 0 3 0 0 0.000161 NaN NaN 0.000161 0.0794
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: 18. Number of genes displayed: 10

rank gene description n cos n_cos N_cos cos_ev p q
1 TP53 tumor protein p53 14 824 14 161504 3219 0 0
2 IDH1 isocitrate dehydrogenase 1 (NADP+), soluble 20 5 20 980 29840 5.9e-15 1e-11
3 IDH2 isocitrate dehydrogenase 2 (NADP+), mitochondrial 18 6 18 1176 1814 7e-15 1e-11
4 PTPN11 protein tyrosine phosphatase, non-receptor type 11 (Noonan syndrome 1) 7 32 6 6272 260 3.7e-14 3.3e-11
5 NRAS neuroblastoma RAS viral (v-ras) oncogene homolog 18 33 18 6468 13364 3.8e-14 3.3e-11
6 NPM1 nucleophosmin (nucleolar phosphoprotein B23, numatrin) 47 41 47 8036 172819 4.7e-14 3.5e-11
7 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 8 52 7 10192 62962 6e-14 3.8e-11
8 FLT3 fms-related tyrosine kinase 3 53 124 49 24304 6227 1.4e-13 7.8e-11
9 RUNX1 runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene) 19 178 17 34888 88 2e-13 9.2e-11
10 WT1 Wilms tumor 1 12 185 10 36260 527 2.1e-13 9.2e-11

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
644 DNMT3A DNA (cytosine-5-)-methyltransferase 3 alpha 54 0 353 355 371 353 355 371
1017 IDH1 isocitrate dehydrogenase 1 (NADP+), soluble 20 0 190 190 190 190 190 190
1018 IDH2 isocitrate dehydrogenase 2 (NADP+), mitochondrial 18 0 121 121 121 121 121 121
819 FLT3 fms-related tyrosine kinase 3 53 0 120 120 136 120 120 136
1458 NRAS neuroblastoma RAS viral (v-ras) oncogene homolog 18 0 45 81 81 45 81 81
1875 RUNX1 runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene) 19 0 12 16 20 12 16 20
1133 KIT v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog 8 0 10 10 10 10 10 10
1147 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 8 0 7 15 15 7 15 15
1190 LILRA3 leukocyte immunoglobulin-like receptor, subfamily A (without TM domain), member 3 3 0 3 3 3 3 3 3
1751 PTPN11 protein tyrosine phosphatase, non-receptor type 11 (Noonan syndrome 1) 7 0 1 2 7 1 2 7

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: 64. 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 q
1 REDUCTIVE_CARBOXYLATE_CYCLE_CO2_FIXATION ACO1, ACO2, FH, IDH1, IDH2, MDH1, MDH2, SDHB, SUCLA2 9 ACO1(1), ACO2(1), IDH1(20), IDH2(18) 2568972 40 37 6 0 33 2 0 5 0 0 <1.00e-15 <2.39e-13
2 HSA04060_CYTOKINE_CYTOKINE_RECEPTOR_INTERACTION Genes involved in cytokine-cytokine receptor interaction ACVR1, ACVR1B, ACVR2A, ACVR2B, AMH, AMHR2, BMP2, BMP7, BMPR1A, BMPR1B, BMPR2, CCL1, CCL11, CCL13, CCL14, CCL15, CCL16, CCL17, CCL18, CCL19, CCL2, CCL20, CCL21, CCL22, CCL23, CCL24, CCL25, CCL26, CCL27, CCL28, CCL3, CCL4, CCL5, CCL7, CCL8, CCR1, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8, CCR9, CD27, CD40, CD40LG, CD70, CLCF1, CNTF, CNTFR, CRLF2, CSF1, CSF1R, CSF2, CSF2RA, CSF2RB, CSF3, CSF3R, CTF1, CX3CL1, CX3CR1, CXCL1, CXCL10, CXCL11, CXCL12, CXCL13, CXCL14, CXCL16, CXCL2, CXCL3, CXCL5, CXCL6, CXCL9, CXCR3, CXCR4, CXCR6, EDA, EDA2R, EDAR, EGF, EGFR, EPO, EPOR, FAS, FASLG, FLJ78302, FLT1, FLT3, FLT3LG, FLT4, GDF5, GH1, GH2, GHR, HGF, IFNA1, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA2, IFNA21, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNAR1, IFNAR2, IFNB1, IFNE1, IFNG, IFNGR1, IFNGR2, IFNK, IFNW1, IL10, IL10RA, IL10RB, IL11, IL11RA, IL12A, IL12B, IL12RB1, IL12RB2, IL13, IL13RA1, IL15, IL15RA, IL17A, IL17B, IL17RA, IL17RB, IL18, IL18R1, IL18RAP, IL19, IL1A, IL1B, IL1R1, IL1R2, IL1RAP, IL2, IL20, IL20RA, IL21, IL21R, IL22, IL22RA1, IL22RA2, IL23A, IL23R, IL24, IL25, IL26, IL28A, IL28B, IL28RA, IL29, IL2RA, IL2RB, IL2RG, IL3, IL3RA, IL4, IL4R, IL5, IL5RA, IL6, IL6R, IL6ST, IL7, IL7R, IL8, IL8RA, IL8RB, IL9, IL9R, INHBA, INHBB, INHBC, INHBE, KDR, KIT, KITLG, LEP, LEPR, LIF, LIFR, LOC728045, LTA, LTB, LTBR, MET, MPL, NGFR, OSM, OSMR, PDGFB, PDGFC, PDGFRA, PDGFRB, PF4, PF4V1, PLEKHO2, PPBP, PRL, PRLR, RELT, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2, TNF, TNFRSF10A, TNFRSF10B, TNFRSF10C, TNFRSF10D, TNFRSF11A, TNFRSF11B, TNFRSF12A, TNFRSF13B, TNFRSF13C, TNFRSF14, TNFRSF17, TNFRSF18, TNFRSF19, TNFRSF1A, TNFRSF1B, TNFRSF21, TNFRSF25, TNFRSF4, TNFRSF6B, TNFRSF8, TNFRSF9, TNFSF10, TNFSF11, TNFSF12, TNFSF13, TNFSF13B, TNFSF14, TNFSF15, TNFSF18, TNFSF4, TNFSF8, TNFSF9, TPO, TSLP, VEGFA, VEGFB, VEGFC, XCL1, XCL2, XCR1 242 ACVR2B(1), CCL11(1), CCL16(1), CCL17(1), CCL20(1), CCL21(1), CD70(1), CLCF1(1), CSF3R(2), CXCL16(1), EGF(1), EGFR(2), FLT1(1), FLT3(53), GHR(1), IFNA16(1), IL23R(1), IL25(1), KDR(2), KIT(8), KITLG(1), MPL(1), PDGFRA(1), PDGFRB(1), PLEKHO2(1), TPO(1) 49336140 88 79 61 10 6 10 3 31 38 0 1.11e-15 2.39e-13
3 CITRATE_CYCLE_TCA_CYCLE ACO1, ACO2, CS, DLD, DLST, DLSTP, FH, IDH1, IDH2, IDH3A, IDH3B, IDH3G, MDH1, MDH2, PC, PCK1, SDHA, SDHA, SDHAL2, SDHB, SUCLA2, SUCLG1, SUCLG2 20 ACO1(1), ACO2(1), DLD(1), IDH1(20), IDH2(18) 5899012 41 38 7 1 33 3 0 5 0 0 1.44e-15 2.39e-13
4 ERYTHPATHWAY Erythropoietin selectively stimulates erythrocyte differentiation from CFU-GEMM cells in bone marrow. CCL3, CSF2, CSF3, EPO, FLT3, IGF1, IL11, IL1A, IL3, IL6, IL9, KITLG, TGFB1, TGFB2, TGFB3 14 FLT3(53), KITLG(1) 2365720 54 53 30 0 0 1 1 17 35 0 1.67e-15 2.39e-13
5 NUCLEAR_RECEPTORS ALK, AR, ESR1, ESR2, ESRRA, HNF4A, NPM1, NR0B1, NR1D2, NR1H2, NR1H3, NR1I2, NR1I3, NR2C2, NR2E1, NR2F1, NR2F2, NR2F6, NR3C1, NR4A1, NR4A2, NR5A1, NR5A2, PGR, PPARA, PPARD, PPARG, RARA, RARB, RARG, ROR1, RORA, RORC, RXRA, RXRB, RXRG, THRA, THRA, NR1D1, THRB, VDR 38 NPM1(47), NR1D1(1), NR1D2(1), NR2E1(2), THRA(1), THRB(1) 11530876 53 51 7 1 1 2 0 2 48 0 2.11e-15 2.39e-13
6 HSA00480_GLUTATHIONE_METABOLISM Genes involved in glutathione metabolism ANPEP, G6PD, GCLC, GCLM, GGT1, GGTL3, GGTL4, GPX1, GPX2, GPX3, GPX4, GPX5, GPX6, GPX7, GSR, GSS, GSTA1, GSTA2, GSTA3, GSTA4, GSTA5, GSTK1, GSTM1, GSTM2, GSTM3, GSTM4, GSTM5, GSTO2, GSTP1, GSTT1, GSTT2, GSTZ1, IDH1, IDH2, MGST1, MGST2, MGST3, OPLAH, TXNDC12 34 G6PD(1), GCLM(1), GPX2(1), GSTK1(2), GSTM3(2), GSTT2(1), IDH1(20), IDH2(18) 5741624 46 44 12 1 34 5 1 6 0 0 2.33e-15 2.39e-13
7 HSA04640_HEMATOPOIETIC_CELL_LINEAGE Genes involved in hematopoietic cell lineage ANPEP, CD14, CD19, CD1A, CD1B, CD1C, CD1D, CD1E, CD2, CD22, CD24, CD33, CD34, CD36, CD37, CD38, CD3D, CD3E, CD3G, CD4, CD44, CD5, CD55, CD59, CD7, CD8A, CD8B, CD9, CR1, CR2, CSF1, CSF1R, CSF2, CSF2RA, CSF3, CSF3R, DNTT, EPO, EPOR, FCER2, FCGR1A, FLT3, FLT3LG, GP1BA, GP1BB, GP5, GP9, GYPA, HLA-DRA, HLA-DRB1, HLA-DRB3, HLA-DRB4, HLA-DRB5, IL11, IL11RA, IL1A, IL1B, IL1R1, IL1R2, IL2RA, IL3, IL3RA, IL4, IL4R, IL5, IL5RA, IL6, IL6R, IL7, IL7R, IL9R, ITGA1, ITGA2, ITGA2B, ITGA3, ITGA4, ITGA5, ITGA6, ITGAM, ITGB3, KIT, KITLG, MME, MS4A1, TFRC, THPO, TNF, TPO 83 CR1(1), CSF3R(2), FLT3(53), ITGA4(1), KIT(8), KITLG(1), MS4A1(1), TPO(1) 23867508 68 65 41 3 2 3 1 24 38 0 3.11e-15 2.74e-13
8 HSA00720_REDUCTIVE_CARBOXYLATE_CYCLE Genes involved in reductive carboxylate cycle (CO2 fixation) ACLY, ACO1, ACO2, ACSS1, ACSS2, FH, IDH1, IDH2, LOC441996, MDH1, MDH2, SUCLA2 11 ACO1(1), ACO2(1), IDH1(20), IDH2(18) 3847088 40 37 6 0 33 2 0 5 0 0 3.66e-15 2.82e-13
9 METHIONINE_METABOLISM AHCY, BHMT, CBS, CTH, DNMT1, DNMT2, DNMT3A, DNMT3B, MARS, MARS2, MAT1A, MAT2B, MTR 12 CBS(1), DNMT1(2), DNMT3A(54), DNMT3B(2), MAT1A(1) 4816504 60 53 34 0 34 2 4 6 14 0 4.44e-15 2.87e-13
10 HSA00020_CITRATE_CYCLE Genes involved in citrate cycle (TCA cycle) ACLY, ACO1, ACO2, CLYBL, CS, DLD, DLST, FH, IDH1, IDH2, IDH3A, IDH3B, IDH3G, LOC283398, LOC441996, MDH1, MDH2, OGDH, OGDHL, PC, PCK1, PCK2, SDHA, SDHB, SDHC, SDHD, SUCLA2, SUCLG1, SUCLG2 27 ACO1(1), ACO2(1), DLD(1), IDH1(20), IDH2(18) 8582448 41 38 7 3 33 3 0 5 0 0 4.66e-15 2.87e-13

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 q
1 HSA00480_GLUTATHIONE_METABOLISM Genes involved in glutathione metabolism ANPEP, G6PD, GCLC, GCLM, GGT1, GGTL3, GGTL4, GPX1, GPX2, GPX3, GPX4, GPX5, GPX6, GPX7, GSR, GSS, GSTA1, GSTA2, GSTA3, GSTA4, GSTA5, GSTK1, GSTM1, GSTM2, GSTM3, GSTM4, GSTM5, GSTO2, GSTP1, GSTT1, GSTT2, GSTZ1, IDH1, IDH2, MGST1, MGST2, MGST3, OPLAH, TXNDC12 32 G6PD(1), GCLM(1), GPX2(1), GSTK1(2), GSTM3(2), GSTT2(1) 5262208 8 8 8 1 1 3 1 3 0 0 0.0059 1
2 ERBB3PATHWAY Neuregulins bind to the receptor tyrosine kinases ErbB3 and ErbB4, surface-localized receptors whose overexpression induces tumor formation. EGF, EGFR, ERBB3, NRG1, UBE2D1 5 EGF(1), EGFR(2), ERBB3(2), UBE2D1(1) 2949996 6 6 6 1 1 1 0 3 1 0 0.0093 1
3 HSA05130_PATHOGENIC_ESCHERICHIA_COLI_INFECTION_EHEC Genes involved in pathogenic Escherichia coli infection - EHEC ABL1, ACTB, ACTG1, ARHGEF2, ARPC5, ARPC5L, CD14, CDC42, CDH1, CLDN1, CTNNB1, CTTN, EZR, FYN, HCLS1, ITGB1, KRT18, LOC643224, LOC654264, LY96, NCK1, NCK2, NCL, OCLN, PRKCA, RHOA, ROCK1, ROCK2, TLR4, TLR5, TUBA1A, TUBA1B, TUBA1C, TUBA3C, TUBA3D, TUBA3E, TUBA4A, TUBA8, TUBAL3, TUBB, TUBB1, TUBB2A, TUBB2B, TUBB2C, TUBB3, TUBB4, TUBB4Q, TUBB6, TUBB8, WAS, WASL, YWHAQ, YWHAZ 51 ABL1(2), CDC42(1), EZR(1), HCLS1(1), LY96(1), TLR4(1), TUBA1A(1), TUBA1B(1), TUBA3C(2), TUBB3(1), TUBB4(1), TUBB6(1), TUBB8(1), YWHAZ(1) 15290156 16 16 16 5 4 3 2 6 1 0 0.01 1
4 HSA05131_PATHOGENIC_ESCHERICHIA_COLI_INFECTION_EPEC Genes involved in pathogenic Escherichia coli infection - EPEC ABL1, ACTB, ACTG1, ARHGEF2, ARPC5, ARPC5L, CD14, CDC42, CDH1, CLDN1, CTNNB1, CTTN, EZR, FYN, HCLS1, ITGB1, KRT18, LOC643224, LOC654264, LY96, NCK1, NCK2, NCL, OCLN, PRKCA, RHOA, ROCK1, ROCK2, TLR4, TLR5, TUBA1A, TUBA1B, TUBA1C, TUBA3C, TUBA3D, TUBA3E, TUBA4A, TUBA8, TUBAL3, TUBB, TUBB1, TUBB2A, TUBB2B, TUBB2C, TUBB3, TUBB4, TUBB4Q, TUBB6, TUBB8, WAS, WASL, YWHAQ, YWHAZ 51 ABL1(2), CDC42(1), EZR(1), HCLS1(1), LY96(1), TLR4(1), TUBA1A(1), TUBA1B(1), TUBA3C(2), TUBB3(1), TUBB4(1), TUBB6(1), TUBB8(1), YWHAZ(1) 15290156 16 16 16 5 4 3 2 6 1 0 0.01 1
5 GLUTATHIONE_METABOLISM ANPEP, G6PD, GCLC, GCLM, GGT1, GPX1, GPX2, GPX3, GPX4, GPX5, GSS, GSTA1, GSTA2, GSTA3, GSTA4, GSTM1, GSTM2, GSTM3, GSTM4, GSTM5, GSTO2, GSTP1, GSTT1, GSTT2, GSTZ1, IDH1, IDH2, MGST1, MGST2, MGST3, PGD 27 G6PD(1), GCLM(1), GPX2(1), GSTM3(2), GSTT2(1), PGD(1) 4664800 7 7 7 1 0 4 1 2 0 0 0.018 1
6 ST_P38_MAPK_PATHWAY p38 is a MAP kinase regulated by cytokines and cellular stress. AKT1, ATF1, CDC42, CREB1, CREB3, CREB5, DUSP1, DUSP10, EEF2K, EIF4E, ELK1, GADD45A, HSPB1, IL1R1, MAP2K3, MAP2K4, MAP2K6, MAP3K10, MAP3K4, MAP3K5, MAP3K7, MAP3K7IP1, MAP3K7IP2, MAPK1, MAPK11, MAPK12, MAPK13, MAPK14, MAPKAPK2, MAPKAPK5, MKNK1, MKNK2, MYEF2, NFKB1, NR2C2, SRF, TRAF6 32 CDC42(1), DUSP1(1), MAP2K3(1), MAP3K4(4), MAPK1(1), MAPKAPK5(1), MKNK1(1), MKNK2(1) 9098908 11 10 9 3 3 1 2 1 4 0 0.022 1
7 ERKPATHWAY Cell growth is promoted by Ras activation of the anti-apoptotic p44/42 MAP kinase pathway. DPM2, EGFR, ELK1, GNAS, GNB1, GNGT1, GRB2, HRAS, IGF1R, ITGB1, KLK2, MAP2K1, MAP2K2, MAPK1, MAPK3, MKNK1, MKNK2, MYC, NGFB, NGFR, PDGFRA, PPP2CA, PTPRR, RAF1, RPS6KA1, RPS6KA5, SHC1, SOS1, SRC, STAT3 28 EGFR(2), GNB1(1), MAPK1(1), MKNK1(1), MKNK2(1), MYC(1), PDGFRA(1), RPS6KA1(1), SHC1(1), SOS1(1) 9014432 11 10 11 3 3 3 0 4 1 0 0.029 1
8 CLASSICPATHWAY The classic complement pathway is initiated by antibodies and promotes phagocytosis and lysis of foreign cells as well as activating the inflammatory response. C1QA, C1QB, C1QG, C1R, C1S, C2, C3, C4A, C4B, C5, C6, C7, C8A, C9 11 C1QA(1), C1S(1), C2(1), C3(1), C5(1), C7(1) 5066796 6 6 6 1 2 1 0 2 1 0 0.046 1
9 GPCRDB_CLASS_C_METABOTROPIC_GLUTAMATE_PHEROMONE CASR, GABBR1, GPCR5A, GPR51, GPRC5A, GPRC5B, GPRC5C, GPRC5D, GRM1, GRM2, GRM3, GRM4, GRM5, GRM7, GRM8 13 CASR(1), GABBR1(1), GPRC5B(1), GRM3(2), GRM5(1), GRM8(2) 5890780 8 7 8 1 5 0 1 2 0 0 0.047 1
10 HSA04540_GAP_JUNCTION Genes involved in gap junction ADCY1, ADCY2, ADCY3, ADCY4, ADCY5, ADCY6, ADCY7, ADCY8, ADCY9, ADRB1, CDC2, CSNK1D, DRD1, DRD2, EDG2, EGF, EGFR, GJA1, GJD2, GNA11, GNAI1, GNAI2, GNAI3, GNAQ, GNAS, GRB2, GRM1, GRM5, GUCY1A2, GUCY1A3, GUCY1B3, GUCY2C, GUCY2D, GUCY2F, HRAS, HTR2A, HTR2B, HTR2C, ITPR1, ITPR2, ITPR3, KRAS, LOC643224, LOC654264, MAP2K1, MAP2K2, MAP2K5, MAP3K2, MAPK1, MAPK3, MAPK7, NPR1, NPR2, NRAS, PDGFA, PDGFB, PDGFC, PDGFD, PDGFRA, PDGFRB, PLCB1, PLCB2, PLCB3, PLCB4, PRKACA, PRKACB, PRKACG, PRKCA, PRKCB1, PRKCG, PRKG1, PRKG2, PRKX, PRKY, RAF1, SOS1, SOS2, SRC, TJP1, TUBA1A, TUBA1B, TUBA1C, TUBA3C, TUBA3D, TUBA3E, TUBA4A, TUBA8, TUBAL3, TUBB, TUBB1, TUBB2A, TUBB2B, TUBB2C, TUBB3, TUBB4, TUBB4Q, TUBB6, TUBB8 88 ADCY2(1), ADCY3(1), ADCY4(2), ADCY5(1), DRD2(1), EGF(1), EGFR(2), GNAI2(1), GRM5(1), GUCY1B3(2), GUCY2C(1), GUCY2D(1), ITPR1(1), ITPR3(1), MAPK1(1), PDGFRA(1), PDGFRB(1), PLCB3(1), PRKCG(1), PRKG2(1), SOS1(1), TJP1(1), TUBA1A(1), TUBA1B(1), TUBA3C(2), TUBB3(1), TUBB4(1), TUBB6(1), TUBB8(1) 36719228 33 26 33 9 9 11 2 9 2 0 0.048 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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