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.

- Analysis Results (MD5 checksum)

- Auxiliary Data (MD5 checksum)

- MAGE-TAB File (MD5 checksum)

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