Acute Myeloid Leukemia: Mutation Analysis (MutSig v2.0)
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

  • Number of patients in set: 199

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.final_analysis_set.maf

  • Significantly mutated genes (q ≤ 0.1): 52

  • Mutations seen in COSMIC: 234

  • Significantly mutated genes in COSMIC territory: 18

  • Genes with clustered mutations (≤ 3 aa apart): 32

  • Significantly mutated genesets: 58

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

Mutation Preprocessing

  • Read 199 MAFs of type "WashU"

  • Total number of mutations in input MAFs: 5617

  • After removing 98 mutations outside chr1-24: 5519

  • After removing 387 noncoding mutations: 5132

  • After collapsing adjacent/redundant mutations: 5126

Mutation Filtering

  • Number of mutations before filtering: 5126

  • After removing 640 mutations outside gene set: 4486

  • After removing 10 mutations outside category set: 4476

Results
Breakdown of Mutations by Type

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

type count
Frame_Shift_Del 102
Frame_Shift_Ins 118
In_Frame_Del 100
In_Frame_Ins 58
Missense_Mutation 2728
Nonsense_Mutation 191
Nonstop_Mutation 2
Silent 1073
Splice_Site 104
Total 4476
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 802 275075312 2.9e-06 2.9 4.7
*Cp(A/C/T)->T 690 2493147819 2.8e-07 0.28 0.45
A->G 365 2773129874 1.3e-07 0.13 0.21
transver 869 5541353005 1.6e-07 0.16 0.26
indel+null 668 5541353204 1.2e-07 0.12 0.2
double_null 9 5541353204 1.6e-09 0.0016 0.0026
Total 3403 5541353204 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.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_ks = p-value for clustering of mutations (Kolmogorov-Smirnoff test)

  • 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: 52. 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_ks p_cons p_joint p q
1 IDH1 isocitrate dehydrogenase 1 (NADP+), soluble 254123 20 20 2 0 18 0 0 2 0 0 <1.00e-15 2e-07 0.96 0.000011 <0.000 <0.000
2 IDH2 isocitrate dehydrogenase 2 (NADP+), mitochondrial 232631 20 20 2 0 16 3 0 1 0 0 5.44e-15 2e-07 0.16 0.000032 0.000 0.000
3 RUNX1 runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene) 146663 19 17 16 0 1 3 2 3 9 1 4.33e-15 3.8e-06 0.08 0.000015 0.000 0.000
4 WT1 Wilms tumor 1 166364 13 13 9 0 1 1 0 0 10 1 7.22e-15 9.4e-06 0.95 0.000064 0.000 0.000
5 U2AF1 U2 small nuclear RNA auxiliary factor 1 154822 10 10 3 0 0 6 0 4 0 0 8.99e-15 0.000013 0.0069 0.000022 0.000 0.000
6 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 140693 9 9 5 0 0 4 1 4 0 0 2.78e-15 0.0048 0.2 0.0052 5.55e-16 1.44e-12
7 FLT3 fms-related tyrosine kinase 3 603169 53 52 29 0 0 1 1 16 35 0 4.66e-15 2e-07 2e-07 0 <1.00e-15 <1.44e-12
8 DNMT3A DNA (cytosine-5-)-methyltransferase 3 alpha 517997 55 50 28 0 33 2 2 4 14 0 <1.00e-15 2e-07 2e-07 0 <1.00e-15 <1.44e-12
9 NPM1 nucleophosmin (nucleolar phosphoprotein B23, numatrin) 185269 47 47 1 0 0 0 0 0 47 0 1.22e-15 2e-07 2e-07 0 <1.00e-15 <1.44e-12
10 NRAS neuroblastoma RAS viral (v-ras) oncogene homolog 116614 18 18 6 0 0 9 1 8 0 0 4.55e-15 2e-07 0.13 0 <1.00e-15 <1.44e-12
11 OR5H6 olfactory receptor, family 5, subfamily H, member 6 195418 4 4 1 2 0 0 0 0 4 0 3.39e-06 4e-07 0.034 0 <1.00e-15 <1.44e-12
12 MPRIP myosin phosphatase Rho interacting protein 375911 3 3 1 0 0 0 0 0 3 0 0.00127 2e-07 0.99 0 <1.00e-15 <1.44e-12
13 TP53 tumor protein p53 260889 15 11 15 1 3 2 4 1 5 0 7.44e-15 0.0074 0.18 0.02 5.55e-15 7.38e-12
14 TET2 tet oncogene family member 2 696898 17 15 17 1 0 1 0 2 9 5 6.77e-15 0.06 0.096 0.049 1.22e-14 1.51e-11
15 AP3S1 adaptor-related protein complex 3, sigma 1 subunit 106067 3 3 1 0 0 0 0 0 3 0 1.09e-05 2e-06 0.078 1.2e-06 3.40e-10 3.91e-07
16 PTPN11 protein tyrosine phosphatase, non-receptor type 11 (Noonan syndrome 1) 362976 7 7 6 0 0 3 1 3 0 0 5.58e-10 0.077 0.13 0.034 4.89e-10 5.27e-07
17 CYP21A2 cytochrome P450, family 21, subfamily A, polypeptide 2 205567 4 4 1 0 0 4 0 0 0 0 2.85e-06 2e-07 1 1e-05 7.33e-10 7.25e-07
18 KIT v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog 591229 8 7 5 0 1 0 0 5 2 0 4.97e-09 0.0096 0.023 0.006 7.56e-10 7.25e-07
19 PHF6 PHD finger protein 6 246561 6 6 6 0 0 1 0 1 4 0 4.56e-10 0.48 0.067 0.17 1.89e-09 1.72e-06
20 SCRN3 secernin 3 259297 3 3 1 0 0 0 0 0 3 0 0.000262 8e-07 0.93 1.4e-06 8.33e-09 7.19e-06
21 LILRA3 leukocyte immunoglobulin-like receptor, subfamily A (without TM domain), member 3 268252 3 3 1 1 0 0 0 3 0 0 0.000171 1.2e-06 0.71 4.6e-06 1.72e-08 1.42e-05
22 C17orf97 chromosome 17 open reading frame 97 168553 5 5 4 1 0 0 1 4 0 0 1.51e-08 0.13 1 0.2 6.06e-08 4.76e-05
23 ETV6 ets variant gene 6 (TEL oncogene) 276809 5 5 5 0 0 0 1 1 3 0 6.43e-08 0.083 0.068 0.049 6.49e-08 4.87e-05
24 ARSD arylsulfatase D 356608 2 2 1 0 0 0 0 2 0 0 0.00652 0.00066 0.000059 8e-07 1.05e-07 7.53e-05
25 NFKBIZ nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, zeta 380488 3 3 1 0 0 0 0 0 3 0 0.000903 0.000026 0.66 0.000026 4.39e-07 0.000303
26 ZNF626 zinc finger protein 626 326559 2 2 1 0 0 0 0 0 2 0 0.00524 0.0006 0.00048 0.000023 2.03e-06 0.00135
27 C16orf71 chromosome 16 open reading frame 71 278600 2 2 1 0 0 0 0 0 2 0 0.00185 0.00064 0.00089 0.00011 3.37e-06 0.00216
28 NOTCH2NL Notch homolog 2 (Drosophila) N-terminal like 144673 3 3 2 0 0 0 0 0 3 0 5.60e-06 NaN NaN NaN 5.60e-06 0.00346
29 SMC3 structural maintenance of chromosomes 3 746449 6 6 6 0 1 1 1 1 2 0 4.45e-07 0.78 0.31 1 6.95e-06 0.00414
30 FAM5C family with sequence similarity 5, member C 463471 6 5 6 0 4 1 0 1 0 0 6.99e-07 0.74 0.52 0.85 9.12e-06 0.00509
31 MUC4 mucin 4, cell surface associated 1002562 10 7 8 6 1 0 1 5 3 0 1.45e-06 0.24 0.86 0.41 9.13e-06 0.00509
32 SMC1A structural maintenance of chromosomes 1A 752419 5 5 5 0 1 0 1 2 1 0 1.34e-05 0.83 0.02 0.11 2.09e-05 0.0113
33 SKA3 spindle and kinetochore associated complex subunit 3 241785 2 2 1 0 0 0 0 0 2 0 0.00313 0.00076 0.39 0.00058 2.58e-05 0.0135
34 C5orf25 chromosome 5 open reading frame 25 254123 3 3 2 0 1 2 0 0 0 0 2.71e-05 NaN NaN NaN 2.71e-05 0.0136
35 CSPG4 chondroitin sulfate proteoglycan 4 659486 3 3 3 2 1 1 0 1 0 0 0.00271 0.000082 0.38 0.00072 2.76e-05 0.0136
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 15 823 15 163777 3379 0 0
2 IDH1 isocitrate dehydrogenase 1 (NADP+), soluble 20 3 20 597 29840 2.4e-15 5.3e-12
3 IDH2 isocitrate dehydrogenase 2 (NADP+), mitochondrial 20 6 20 1194 2000 4.6e-15 6.6e-12
4 NRAS neuroblastoma RAS viral (v-ras) oncogene homolog 18 28 18 5572 13364 2.2e-14 1.7e-11
5 NPM1 nucleophosmin (nucleolar phosphoprotein B23, numatrin) 47 29 47 5771 172819 2.2e-14 1.7e-11
6 PTPN11 protein tyrosine phosphatase, non-receptor type 11 (Noonan syndrome 1) 7 31 6 6169 260 2.4e-14 1.7e-11
7 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 9 51 8 10149 62973 3.9e-14 2.5e-11
8 FLT3 fms-related tyrosine kinase 3 53 114 49 22686 6227 8.7e-14 4.8e-11
9 RUNX1 runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene) 19 175 17 34825 88 1.3e-13 5.6e-11
10 KIT v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog 8 183 7 36417 3934 1.4e-13 5.6e-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
659 DNMT3A DNA (cytosine-5-)-methyltransferase 3 alpha 55 0 380 382 398 380 382 398
1036 IDH1 isocitrate dehydrogenase 1 (NADP+), soluble 20 0 190 190 190 190 190 190
1037 IDH2 isocitrate dehydrogenase 2 (NADP+), mitochondrial 20 0 139 139 139 139 139 139
835 FLT3 fms-related tyrosine kinase 3 53 0 120 120 136 120 120 136
1486 NRAS neuroblastoma RAS viral (v-ras) oncogene homolog 18 0 45 81 81 45 81 81
1915 RUNX1 runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene) 19 0 12 16 20 12 16 20
1154 KIT v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog 8 0 10 10 10 10 10 10
1168 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 9 0 7 15 15 7 15 15
1211 LILRA3 leukocyte immunoglobulin-like receptor, subfamily A (without TM domain), member 3 3 0 3 3 3 3 3 3
1787 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: 58. 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 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(20) 8713812 43 40 7 3 34 4 0 5 0 0 <1.00e-15 <3.08e-13
2 METHIONINE_METABOLISM AHCY, BHMT, CBS, CTH, DNMT1, DNMT2, DNMT3A, DNMT3B, MARS, MARS2, MAT1A, MAT2B, MTR 12 CBS(1), DNMT1(2), DNMT3A(55), DNMT3B(2), MAT1A(1) 4890226 61 54 34 0 35 2 4 6 14 0 1.22e-15 3.08e-13
3 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) 2401930 54 53 30 0 0 1 1 17 35 0 1.67e-15 3.08e-13
4 REDUCTIVE_CARBOXYLATE_CYCLE_CO2_FIXATION ACO1, ACO2, FH, IDH1, IDH2, MDH1, MDH2, SDHB, SUCLA2 9 ACO1(1), ACO2(1), IDH1(20), IDH2(20) 2608293 42 39 6 0 34 3 0 5 0 0 2.89e-15 3.08e-13
5 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), IL1R1(1), IL23R(1), IL25(1), KDR(2), KIT(8), KITLG(1), MPL(1), PDGFRA(1), PDGFRB(1), PLEKHO2(1), TPO(1) 50091285 89 80 62 10 7 10 3 31 38 0 3.22e-15 3.08e-13
6 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 29 G6PD(1), GCLM(1), GPX2(1), GSTM3(2), GSTT2(1), IDH1(20), IDH2(20), PGD(1) 5222954 47 45 11 1 34 7 1 5 0 0 3.22e-15 3.08e-13
7 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 17 JAK2(1), TP53(15), USH1C(1), WT1(13) 5164846 30 26 26 3 4 4 4 2 15 1 4.00e-15 3.08e-13
8 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(20) 5829506 48 46 12 1 35 6 1 6 0 0 4.22e-15 3.08e-13
9 HSA00271_METHIONINE_METABOLISM Genes involved in methionine metabolism AHCY, AMD1, BHMT, CBS, CTH, DNMT1, DNMT3A, DNMT3B, KIAA0828, MARS, MARS2, MAT1A, MAT2B, MTAP, MTFMT, MTR, SRM, TAT 17 CBS(1), DNMT1(2), DNMT3A(55), DNMT3B(2), MAT1A(1) 5761050 61 54 34 0 35 2 4 6 14 0 4.88e-15 3.08e-13
10 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) 11707369 53 51 7 1 1 2 0 2 48 0 5.11e-15 3.08e-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) 5342752 8 8 8 1 1 3 1 3 0 0 0.0067 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) 2995149 6 6 6 1 1 1 0 3 1 0 0.01 1
3 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), IL1R1(1), MAP2K3(1), MAP3K4(4), MAPK1(1), MAPKAPK5(1), MKNK1(1), MKNK2(1) 9238177 12 11 10 3 4 1 2 1 4 0 0.011 1
4 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) 15524189 16 16 16 6 4 3 2 6 1 0 0.012 1
5 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) 15524189 16 16 16 6 4 3 2 6 1 0 0.012 1
6 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) 4736200 7 7 7 1 0 4 1 2 0 0 0.02 1
7 HSA04080_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION Genes involved in neuroactive ligand-receptor interaction ADCYAP1R1, ADORA1, ADORA2A, ADORA2B, ADORA3, ADRA1A, ADRA1B, ADRA2A, ADRA2B, ADRA2C, ADRB1, ADRB2, ADRB3, AGTR1, AGTR2, AGTRL1, AVPR1A, AVPR1B, AVPR2, BDKRB1, BDKRB2, BRS3, C3AR1, C5AR1, CALCR, CALCRL, CCKAR, CCKBR, CGA, CHRM1, CHRM2, CHRM3, CHRM4, CHRM5, CNR1, CNR2, CRHR1, CRHR2, CTSG, CYSLTR1, CYSLTR2, DRD1, DRD2, DRD3, DRD4, DRD5, EDG1, EDG2, EDG3, EDG4, EDG5, EDG6, EDG7, EDG8, EDNRA, EDNRB, F2, F2R, F2RL1, F2RL2, F2RL3, FPR1, FPRL1, FPRL2, FSHB, FSHR, GABBR1, GABBR2, GABRA1, GABRA2, GABRA3, GABRA4, GABRA5, GABRA6, GABRB1, GABRB2, GABRB3, GABRD, GABRE, GABRG1, GABRG2, GABRG3, GABRP, GABRQ, GABRR1, GABRR2, GALR1, GALR2, GALR3, GCGR, GH1, GH2, GHR, GHRHR, GHSR, GIPR, GLP1R, GLP2R, GLRA1, GLRA2, GLRA3, GLRB, GNRHR, GPR156, GPR23, GPR35, GPR50, GPR63, GPR83, GRIA1, GRIA2, GRIA3, GRIA4, GRID1, GRID2, GRIK1, GRIK2, GRIK3, GRIK4, GRIK5, GRIN1, GRIN2A, GRIN2B, GRIN2C, GRIN2D, GRIN3A, GRIN3B, GRM1, GRM2, GRM3, GRM4, GRM5, GRM6, GRM7, GRM8, GRPR, GZMA, HCRTR1, HCRTR2, HRH1, HRH2, HRH3, HRH4, HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR4, HTR5A, HTR6, HTR7, KISS1R, LEP, LEPR, LHB, LHCGR, LTB4R, LTB4R2, MAS1, MC1R, MC2R, MC3R, MC4R, MC5R, MCHR1, MCHR2, MLNR, MTNR1A, MTNR1B, NMBR, NMUR1, NMUR2, NPBWR1, NPBWR2, NPFFR1, NPFFR2, NPY1R, NPY2R, NPY5R, NR3C1, NTSR1, NTSR2, OPRD1, OPRK1, OPRL1, OPRM1, OXTR, P2RX1, P2RX2, P2RX3, P2RX4, P2RX5, P2RX7, P2RXL1, P2RY1, P2RY10, P2RY11, P2RY13, P2RY14, P2RY2, P2RY4, P2RY5, P2RY6, P2RY8, PARD3, PPYR1, PRL, PRLHR, PRLR, PRSS1, PRSS2, PRSS3, PTAFR, PTGDR, PTGER1, PTGER2, PTGER3, PTGER4, PTGFR, PTGIR, PTH2R, PTHR1, RXFP1, RXFP2, SCTR, SSTR1, SSTR2, SSTR3, SSTR4, SSTR5, TAAR1, TAAR2, TAAR5, TAAR6, TAAR8, TAAR9, TACR1, TACR2, TACR3, TBXA2R, THRA, THRB, TRHR, TRPV1, TSHB, TSHR, TSPO, UTS2R, VIPR1, VIPR2 220 ADRA1A(1), BRS3(1), C5AR1(1), CRHR2(1), CTSG(1), DRD2(1), F2RL1(1), GABBR1(1), GABRA4(1), GABRB1(1), GABRG2(1), GABRR1(1), GHR(1), GLRA1(1), GNRHR(1), GPR156(1), GPR50(1), GRID1(2), GRIK2(3), GRIK3(2), GRIK4(3), GRIK5(1), GRIN3A(1), GRM3(2), GRM5(1), GRM6(2), GRM8(2), HTR5A(1), MCHR2(1), NMUR2(3), NTSR2(1), OPRM1(1), P2RX7(1), P2RY1(1), P2RY2(2), PARD3(1), PRSS3(1), SCTR(1), SSTR4(1), THRA(1), THRB(1), VIPR1(2) 60973003 55 41 55 16 18 18 3 13 3 0 0.027 1
8 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) 9152408 11 10 11 3 3 3 0 4 1 0 0.033 1
9 HSA00980_METABOLISM_OF_XENOBIOTICS_BY_CYTOCHROME_P450 Genes involved in metabolism of xenobiotics by cytochrome P450 ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH6, ADH7, ADHFE1, AKR1C1, AKR1C2, AKR1C3, AKR1C4, ALDH1A3, ALDH3A1, ALDH3B1, ALDH3B2, CYP1A1, CYP1A2, CYP1B1, CYP2B6, CYP2C18, CYP2C19, CYP2C8, CYP2C9, CYP2E1, CYP2F1, CYP2S1, CYP3A4, CYP3A43, CYP3A5, CYP3A7, DHDH, EPHX1, GSTA1, GSTA2, GSTA3, GSTA4, GSTA5, GSTK1, GSTM1, GSTM2, GSTM3, GSTM4, GSTM5, GSTO2, GSTP1, GSTT1, GSTT2, GSTZ1, MGST1, MGST2, MGST3, UGT1A1, UGT1A10, UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT2A1, UGT2A3, UGT2B10, UGT2B11, UGT2B15, UGT2B17, UGT2B28, UGT2B4, UGT2B7 69 ADH1C(1), ADHFE1(1), ALDH1A3(1), CYP1A2(1), GSTK1(2), GSTM3(2), GSTT2(1), UGT1A10(1), UGT2A3(1), UGT2B28(1), UGT2B4(1) 16213525 13 13 13 6 5 4 1 2 1 0 0.044 1
10 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 14 ABL1(2), MDM2(1), MYC(1), POLR1A(2), POLR1B(1) 5574587 7 7 7 1 2 1 1 2 1 0 0.044 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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