Mutation Analysis (MutSig v2.0 and MutSigCV v0.9 merged result)

Acute Myeloid Leukemia (Primary blood derived cancer - Peripheral blood)

23 May 2013 | analyses__2013_05_23

Maintainer Information

Citation Information

Maintained by Dan DiCara (Broad Institute)

Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Mutation Analysis (MutSig v2.0 and MutSigCV v0.9 merged result). Broad Institute of MIT and Harvard. doi:10.7908/C1H9939H

- Overview

+ Introduction

- Summary

MAF used for this analysis:LAML-TB.final_analysis_set.maf
Significantly mutated genes (q ≤ 0.1): 6
Mutations seen in COSMIC: 238
Significantly mutated genes in COSMIC territory: 19
Significantly mutated genesets: 69

Mutation Preprocessing

Read 197 MAFs of type "WashU"
Total number of mutations in input MAFs: 2585
After removing 41 mutations outside chr1-24: 2544
After removing 1 blacklisted mutations: 2543
After removing 104 noncoding mutations: 2439

Mutation Filtering

Number of mutations before filtering: 2439
After removing 204 mutations outside gene set: 2235
After removing 14 mutations outside category set: 2221

- Results

+ Breakdown of Mutations by Type

type	count
Frame_Shift_Del	51
Frame_Shift_Ins	110
In_Frame_Del	8
In_Frame_Ins	43
Missense_Mutation	1401
Nonsense_Mutation	108
Silent	450
Splice_Site	50
Total	2221

+ Breakdown of Mutation Rates by Category Type

category	n	N	rate	rate_per_mb	relative_rate
*CpG->T	509	272310736	1.9e-06	1.9	5.8
*Cp(A/C/T)->T	312	2468091057	1.3e-07	0.13	0.39
A->G	182	2745259222	6.6e-08	0.066	0.21
transver	398	5485661015	7.3e-08	0.073	0.22
indel+null	357	5485661212	6.5e-08	0.065	0.2
double_null	13	5485661212	2.4e-09	0.0024	0.0073
Total	1771	5485661212	3.2e-07	0.32	1

+ Target Coverage for Each Individual

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

+ CoMut Plot

+ 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_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: 6. 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_cons	p_joint	p_cv	p	q
1	DNMT3A	DNA (cytosine-5-)-methyltransferase 3 alpha	512791	57	51	29	0	34	2	3	4	14	0	0	0	1	0	0
2	U2AF1	U2 small nuclear RNA auxiliary factor 1	153266	8	8	2	0	0	5	0	3	0	0	0.00038	0	1	0	0
3	FLT3	fms-related tyrosine kinase 3	597107	56	56	30	0	0	0	1	16	39	0	4.2e-06	0	1	0	0
4	IDH2	isocitrate dehydrogenase 2 (NADP+), mitochondrial	230293	20	20	2	0	16	3	0	1	0	0	0.74	0	1	0	0
5	IDH1	isocitrate dehydrogenase 1 (NADP+), soluble	251569	19	19	2	0	17	0	0	2	0	0	0.98	0	1	0	0
6	NPM1	nucleophosmin (nucleolar phosphoprotein B23, numatrin)	183407	54	54	7	0	0	0	1	0	52	1	0	0	1	0	0
7	NRAS	neuroblastoma RAS viral (v-ras) oncogene homolog	115442	15	15	6	0	0	8	1	6	0	0	0.28	4.2e-06	1	0.000056	0.14
8	WT1	Wilms tumor 1	164692	12	12	10	0	1	1	0	0	9	1	1	0.00022	1	0.002	1
9	RUNX1	runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene)	145189	20	18	16	0	2	3	2	2	10	1	0.016	0.0031	1	0.021	1
10	SMG1	smg-1 homolog, phosphatidylinositol 3-kinase-related kinase (C. elegans)	2065151	3	3	3	0	0	1	1	1	0	0	0.12	0.0082	1	0.048	1
11	KIT	v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog	585287	9	8	5	0	1	0	0	6	1	1	0.1	0.017	1	0.086	1
12	EZH2	enhancer of zeste homolog 2 (Drosophila)	459010	3	3	3	0	1	0	0	0	1	1	0.83	0.026	1	0.12	1
13	TRPM3	transient receptor potential cation channel, subfamily M, member 3	1053359	2	2	2	0	1	1	0	0	0	0	0.47	0.028	1	0.13	1
14	GATA2	GATA binding protein 2	159964	2	2	2	0	0	1	0	1	0	0	0.026	0.036	1	0.16	1
15	FCGBP	Fc fragment of IgG binding protein	2259984	3	3	3	2	1	1	0	1	0	0	0.086	0.037	1	0.16	1
16	KRAS	v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog	139279	8	8	6	0	0	4	1	3	0	0	0.65	0.039	1	0.16	1
17	TP53	tumor protein p53	258267	18	15	18	1	3	2	3	2	8	0	0.32	0.04	1	0.17	1
18	GSTK1	glutathione S-transferase kappa 1	172769	2	2	2	0	1	0	0	1	0	0	0.23	0.046	1	0.19	1
19	DOCK2	dedicator of cytokinesis 2	1113838	2	2	2	0	0	0	1	0	1	0	0.017	0.068	1	0.25	1
20	PKD1L2	polycystic kidney disease 1-like 2	1191259	2	2	2	2	1	1	0	0	0	0	0.074	0.075	1	0.27	1
21	CBL	Cas-Br-M (murine) ecotropic retroviral transforming sequence	509442	2	2	2	1	0	0	1	0	1	0	0.41	0.084	1	0.29	1
22	PTPN11	protein tyrosine phosphatase, non-receptor type 11 (Noonan syndrome 1)	359328	9	9	9	0	0	3	2	4	0	0	0.3	0.085	1	0.29	1
23	NR2E1	nuclear receptor subfamily 2, group E, member 1	182225	2	2	2	0	0	1	0	1	0	0	0.092	0.1	1	0.33	1
24	PDCD2L	programmed cell death 2-like	161934	2	2	2	0	0	0	2	0	0	0	0.094	0.1	1	0.34	1
25	HNRNPK	heterogeneous nuclear ribonucleoprotein K	293530	2	2	2	0	0	0	0	0	1	1	0.8	0.11	1	0.34	1
26	CSMD3	CUB and Sushi multiple domains 3	2259590	2	2	2	0	1	1	0	0	0	0	0.15	0.11	1	0.36	1
27	COL12A1	collagen, type XII, alpha 1	1846875	3	3	3	1	1	1	0	1	0	0	0.013	0.11	1	0.36	1
28	KIAA1683	KIAA1683	543523	2	2	2	1	0	0	1	0	1	0	0.078	0.12	1	0.37	1
29	PHACTR1	phosphatase and actin regulator 1	323868	3	3	2	0	0	0	0	1	2	0	0.72	0.12	1	0.38	1
30	NF1	neurofibromin 1 (neurofibromatosis, von Recklinghausen disease, Watson disease)	1721977	2	2	2	0	1	0	0	0	1	0	0.55	0.14	1	0.42	1
31	DCHS2	dachsous 2 (Drosophila)	1696761	2	2	2	0	1	0	0	1	0	0	0.12	0.14	1	0.42	1
32	SMC1A	structural maintenance of chromosomes 1A	744857	7	7	7	0	3	0	1	2	1	0	0.041	0.14	1	0.42	1
33	PLCE1	phospholipase C, epsilon 1	1441843	4	4	4	0	0	0	1	3	0	0	0.94	0.14	1	0.42	1
34	SI	sucrase-isomaltase (alpha-glucosidase)	1117384	2	2	2	0	0	0	1	1	0	0	0.26	0.16	1	0.46	1
35	CSMD1	CUB and Sushi multiple domains 1	1689669	4	4	4	0	0	0	0	3	1	0	0.9	0.16	1	0.46	1

+ COSMIC analyses

rank	gene	description	n	cos	n_cos	N_cos	cos_ev	p	q
1	TP53	tumor protein p53	18	824	16	162328	3427	0	0
2	IDH1	isocitrate dehydrogenase 1 (NADP+), soluble	19	5	19	985	28348	5.2e-14	9.1e-11
3	IDH2	isocitrate dehydrogenase 2 (NADP+), mitochondrial	20	6	20	1182	2000	6.3e-14	9.1e-11
4	PTPN11	protein tyrosine phosphatase, non-receptor type 11 (Noonan syndrome 1)	9	32	8	6304	216	3.3e-13	3e-10
5	NRAS	neuroblastoma RAS viral (v-ras) oncogene homolog	15	33	15	6501	11840	3.4e-13	3e-10
6	NPM1	nucleophosmin (nucleolar phosphoprotein B23, numatrin)	54	41	53	8077	112668	4.3e-13	3.1e-10
7	KRAS	v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog	8	52	7	10244	46308	5.4e-13	3.4e-10
8	FLT3	fms-related tyrosine kinase 3	56	124	52	24428	6301	1.3e-12	7e-10
9	RUNX1	runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene)	20	178	18	35066	93	1.8e-12	8.3e-10
10	WT1	Wilms tumor 1	12	185	9	36445	444	1.9e-12	8.3e-10

+ 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: 69. 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	34	GCLM(1), GPX2(1), GSTK1(2), GSTM3(1), IDH1(19), IDH2(20)	5770918	44	42	9	0	34	4	0	6	0	0	<1.00e-15	<2.05e-13
2	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	GCLM(1), GPX2(1), GSTM3(1), IDH1(19), IDH2(20)	5170462	42	40	7	0	33	4	0	5	0	0	<1.00e-15	<2.05e-13
3	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), CCL20(1), CCL21(1), CD70(1), CSF3R(1), EGFR(2), FLT1(1), FLT3(56), IL1R1(1), KDR(2), KIT(9), MPL(1), PDGFRA(1), PDGFRB(1), TPO(1)	49587855	82	78	52	4	7	5	2	27	40	1	1.22e-15	2.05e-13
4	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	DNMT1(1), DNMT3A(57), DNMT3B(1), MAT1A(1)	5703150	60	53	32	0	36	2	3	5	14	0	1.33e-15	2.05e-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(54), NR2E1(2), THRB(1)	11589707	57	56	10	0	1	1	1	1	52	1	2.11e-15	2.25e-13
6	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(1), FLT3(56), HLA-DRB1(1), IL1R1(1), KIT(9), TPO(1)	23989281	70	68	40	1	2	2	1	24	40	1	2.44e-15	2.25e-13
7	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	IDH1(19), IDH2(20)	3866716	39	38	4	0	33	3	0	3	0	0	2.55e-15	2.25e-13
8	METHIONINE_METABOLISM		AHCY, BHMT, CBS, CTH, DNMT1, DNMT2, DNMT3A, DNMT3B, MARS, MARS2, MAT1A, MAT2B, MTR	12	DNMT1(1), DNMT3A(57), DNMT3B(1), MAT1A(1)	4841078	60	53	32	0	36	2	3	5	14	0	3.11e-15	2.39e-13
9	REDUCTIVE_CARBOXYLATE_CYCLE_CO2_FIXATION		ACO1, ACO2, FH, IDH1, IDH2, MDH1, MDH2, SDHB, SUCLA2	9	IDH1(19), IDH2(20)	2582079	39	38	4	0	33	3	0	3	0	0	3.55e-15	2.43e-13
10	KREBPATHWAY	The Krebs (citric acid) cycle takes place in mitochondria, where it extracts energy in the form of electron carriers NADH and FADH2, which drive the electron transport chain.	ACO2, CS, FH, IDH2, MDH1, OGDH, SDHA, SUCLA2	8	IDH2(20)	2741649	20	20	2	0	16	3	0	1	0	0	4.66e-15	2.47e-13

+ Methods & Data

Made with Nozzle